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Barik P, Mondal S. Immunomodulatory effects of metal nanoparticles: current trends and future prospects. NANOSCALE 2025; 17:10433-10461. [PMID: 40202489 DOI: 10.1039/d5nr01030f] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/10/2025]
Abstract
The advent of nanotechnology has steered into a new era of medical advancements, with metal nanoparticles (MNPs) emerging as potent agents for precise regulation of the immune system. This review provides a comprehensive overview of the immunomodulatory roles of MNPs, including gold, silver, and metal oxide nanoparticles, in regulating innate and adaptive immunity. Additionally, we discuss the immunological effects of metal ions and metal complexes, offering a comparative analysis with nanoparticulate systems. We analyse cutting-edge strategies utilising MNPs to optimise vaccine efficacy, achieve targeted delivery to immune cells, and orchestrate inflammatory responses. Additionally, we discuss the therapeutic potential of MNPs in combating autoimmune diseases, cancers, and infectious agents, which is evaluated within the framework of precision medicine. Furthermore, we critically assess challenges such as biocompatibility, potential toxicity, and regulatory hurdles. Finally, we propose future directions for integrating MNPs with advanced delivery systems and other nanomaterials to propel the frontiers of immunotherapy. This review aims to provide a foundational understanding of MNP-mediated immunomodulation, inspiring further research and development in this burgeoning field.
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Affiliation(s)
- Puspendu Barik
- Materials Science and Engineering Program, College of Arts and Sciences, American University of Sharjah, Sharjah, 26666, United Arab Emirates
- Department of Physics, College of Arts and Sciences, American University of Sharjah, Sharjah, 26666, United Arab Emirates
| | - Samiran Mondal
- Department of Chemistry, Rammohan College (University of Calcutta), 102/1-Raja Rammohan Sarani, Kolkata 700009, West Bengal, India.
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2
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Zou K, Du L, Qin J, Zhou J, Xiao Y, Song X, Liu H, Wang X. Titanium dioxide nanoparticles disturb glucose homeostasis in association with impaired enteroendocrine cell differentiation. Food Chem Toxicol 2025; 202:115504. [PMID: 40318823 DOI: 10.1016/j.fct.2025.115504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2025] [Revised: 04/07/2025] [Accepted: 04/30/2025] [Indexed: 05/07/2025]
Abstract
Gut hormones secreted by enteroendocrine cells play a critical role in maintaining glucose homeostasis. However, the adverse endocrine effects related to glucose homeostasis caused by food additives are not well understood. This work aims to investigate the effects of titanium dioxide nanoparticles (TiO2 NPs) in comparison to titanium dioxide microparticles (TiO2 MPs) on glucose homeostasis, with a specific focus on the enteroendocrine cells and gut hormones. Our research found that exposure to 1 % (w/w) TiO2 NPs, unlike TiO2 MPs, resulted in elevated blood glucose levels and impaired glucose tolerance in mice. Notably, 1 % (w/w) TiO2 NPs significantly influenced the differentiation of the intestinal epithelium while not causing any notable histological changes or affecting cell proliferation in the mouse ileum. Furthermore, the levels of gut hormones, including glucagon-like peptide-1 (GLP-1), peptide YY (PYY) and cholecystokinin (CCK), released from mouse ileum tissues were also significantly reduced following exposure to 1 % (w/w) TiO2 NPs. Using the intestinal organoid model, we also discovered that 20 μg/mL TiO2 NPs impaired enteroendocrine cell differentiation, reduced basal GLP-1 secretion levels, and disrupted the GLP-1 secretion response to nutrient stimuli. Our research highlights the detrimental effects of TiO2 NPs as potential intestinal endocrine disruptor and underscores the need to optimize their particle size for safe use in the food industry.
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Affiliation(s)
- Kai Zou
- School of Advanced Materials Engineering, Jiaxing Nanhu University, Jiaxing, 314000, China; Jiaxing Key Laboratory for Research and Application of Green and Low-carbon Advanced Materials, Jiaxing, 314000, China
| | - Linna Du
- School of Advanced Materials Engineering, Jiaxing Nanhu University, Jiaxing, 314000, China
| | - Jing Qin
- School of Advanced Materials Engineering, Jiaxing Nanhu University, Jiaxing, 314000, China
| | - Jiacheng Zhou
- School of Advanced Materials Engineering, Jiaxing Nanhu University, Jiaxing, 314000, China
| | - Yanping Xiao
- School of Advanced Materials Engineering, Jiaxing Nanhu University, Jiaxing, 314000, China
| | - Xixi Song
- School of Advanced Materials Engineering, Jiaxing Nanhu University, Jiaxing, 314000, China
| | - Hongxia Liu
- School of Advanced Materials Engineering, Jiaxing Nanhu University, Jiaxing, 314000, China
| | - Xiu Wang
- School of Advanced Materials Engineering, Jiaxing Nanhu University, Jiaxing, 314000, China; Jiaxing Key Laboratory for Research and Application of Green and Low-carbon Advanced Materials, Jiaxing, 314000, China.
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3
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Li X, Xu S, Su Z, Shao Z, Huang X. Unleashing the Potential of Metal Ions in cGAS-STING Activation: Advancing Nanomaterial-Based Tumor Immunotherapy. ACS OMEGA 2025; 10:11723-11742. [PMID: 40191377 PMCID: PMC11966298 DOI: 10.1021/acsomega.4c10865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Revised: 01/29/2025] [Accepted: 02/03/2025] [Indexed: 04/09/2025]
Abstract
Immunotherapy is a critical modality in cancer treatment with diverse activation pathways. In recent years, the stimulator of interferon genes (STING) signaling pathway has exhibited significant potential in tumor immunotherapy. This pathway exerts notable antitumor effects by activating innate and adaptive immunity and regulating the tumor immune microenvironment. Various metal ions have been identified as effective activators of the STING pathway and, through the design and synthesis of nanodelivery platforms, have been applied in immunotherapy as well as in combination therapies, such as chemotherapy, chemodynamic therapy, photodynamic therapy, and cancer vaccines. Metal nanomaterials showcase unique advantages in immunotherapy; however, there are still aspects that require optimization. This review systematically examines existing metal-based nanomaterials, elaborates on the mechanisms by which different metal ions activate the STING pathway, and discusses their application models in tumor combination therapies. We also provide a comparative analysis of the advantages of metal nanomaterials over other treatment methods. Our exploration highlights the broad application prospects of metal nanomaterials in cancer treatment, offering new insights and directions for the advancement of tumor immunotherapy.
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Affiliation(s)
- Xingyin Li
- Department
of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Shaojie Xu
- Department
of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - Ziliang Su
- Department
of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Zengwu Shao
- Department
of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Xin Huang
- Department
of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
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Yuksel C, Uz YH. Protective effects of N-acetylcysteine against titanium dioxide nanoparticles-induced kidney damage in rats. J Mol Histol 2025; 56:112. [PMID: 40106010 DOI: 10.1007/s10735-025-10395-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2025] [Accepted: 03/06/2025] [Indexed: 03/22/2025]
Abstract
The objective of this study was to evaluate the potential protective effect of N-acetylcysteine (NAC) against kidney damage induced by titanium dioxide nanoparticles (TiO2NP) through biochemical, histological, and immunohistochemical analyses. Forty rats were randomly divided into four groups of 10 animals each. Saline was administered intragastrically to control group for 14 days. In NAC group, 150 mg/kg NAC was injected intraperitoneally for 21 days. In TiO2NP group, TiO2NP at a dose of 50 mg/kg/day, dissolved in saline, was administered intragastrically for 14 days. TiO2NP + NAC group received 50 mg/kg/day TiO2NP for 14 days and 150 mg/kg NAC for 21 days, starting 7 days before TiO2NP administration. At the end of experiment, rats were anesthetized, serum samples were collected for biochemical analysis, and kidney tissue was removed for histological and immunohistochemical analyses. There was no significant change in body weight, kidney weight, or serum urea-creatinine levels between the groups. TiO2NP caused a significant increase in vacuolization and brush border loss scores in tubular cells, as well as scores for congestion and leukocyte infiltration. However, NAC supplementation significantly ameliorated these impairments. Additionally, TiO2NP significantly increased NF-kB, TNF-α, and caspase-3 immunoreactivities, as well as the number of PCNA-positive and TUNEL-positive cells. NAC treatment decreased all immunoreactivities and TUNEL-positive cells, but did not change the number of PCNA-positive cells after TiO2NP exposure. The results of the study showed that the toxic effects of TiO2NP on the kidneys, commonly encountered in daily life, can be mitigated by the anti-inflammatory and anti-apoptotic properties of NAC.
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Affiliation(s)
- Cengiz Yuksel
- Department of Histology and Embryology, Faculty of Medicine, Trakya University, Edirne, Turkey
- Department of Histology and Embryology, Faculty of Medicine, Kirklareli University, Kirklareli, Turkey
| | - Yesim Hulya Uz
- Department of Histology and Embryology, Faculty of Medicine, Trakya University, Edirne, Turkey.
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Khan J, Kim ND, Bromhead C, Truman P, Kruger MC, Mallard BL. Hepatotoxicity of titanium dioxide nanoparticles. J Appl Toxicol 2025; 45:23-46. [PMID: 38740968 PMCID: PMC11634566 DOI: 10.1002/jat.4626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Revised: 04/21/2024] [Accepted: 04/25/2024] [Indexed: 05/16/2024]
Abstract
The food additive E171 (titanium dioxide, TiO2), is widely used in foods, pharmaceuticals and cosmetics. It is a fine white powder, with at least one third of its particles sized in the nanoparticulate (˂100 nm range, TiO2 NPs). The use of E171 is controversial as its relevant risk assessment has never been satisfactorily accomplished. In vitro and in vivo studies have shown dose-dependent toxicity in various organs including the liver. TiO2 NPs have been shown to induce inflammation, cell death and structural and functional changes within the liver. The toxicity of TiO2 NPs in experimental models varies between organs and according to their physiochemical characteristics and parameters such as dosage and route of administration. Among these factors, ingestion is the most significant exposure route, and the liver is a key target organ. The aim of this review is to highlight the reported adverse effects of orally administered TiO2 NPs on the liver and to discuss the controversial state of its toxicity.
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Affiliation(s)
- Jangrez Khan
- School of Health SciencesMassey UniversityPO Box 756Wellington6021New Zealand
| | - Nicholas D. Kim
- School of Health SciencesMassey UniversityPO Box 756Wellington6021New Zealand
| | - Collette Bromhead
- School of Health SciencesMassey UniversityPO Box 756Wellington6021New Zealand
| | - Penelope Truman
- School of Health SciencesMassey UniversityPO Box 756Wellington6021New Zealand
| | - Marlena C. Kruger
- School of Health SciencesMassey UniversityPO Box 756Wellington6021New Zealand
| | - Beth L. Mallard
- School of Health SciencesMassey UniversityPO Box 756Wellington6021New Zealand
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Wang K, Hao Z, Xie J, Ma L, Zhang W, Mo J, Li L, Jin C. Nrf2-dependent hepatoprotective effect of ellagic acid in titanium dioxide nanoparticles-induced liver injury. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 135:156064. [PMID: 39306885 DOI: 10.1016/j.phymed.2024.156064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/04/2024] [Revised: 08/11/2024] [Accepted: 09/15/2024] [Indexed: 12/01/2024]
Abstract
BACKGROUND AND AIMS Previous studies suggest that titanium dioxide nanoparticles (TiO2 NPs) induce liver injury, possibly due to oxidative stress and inflammation. Ellagic acid (EA) is a dietary polyphenol extracted from natural sources and possesses antioxidant and anti-inflammatory properties. Nonetheless, the efficacy of EA in mitigating liver injury induced by TiO2 NPs remains to be elucidated. METHODS Primary hepatocytes and L02 cells were cultured with 45 μM EA and 10 μg/ml TiO2 NPs. Mice were orally administered TiO2 NPs (150 mg kg-1) and EA (25/50/100 mg kg-1) for eight weeks. sulforaphane (SFN) as a positive control to evaluate the inhibitory effect of EA on TiO2 NP-induced liver injury (SFN 10 mg kg-1). RNA sequencing (RNA-seq) was employed to elucidate the mechanisms underlying oxidative stress, inflammation, and liver fibrosis. RESULTS We assessed the impact of EA on cytotoxicity, oxidative stress, inflammation, and fibrosis in both cells and mice exposed to TiO2 NPs for an extended period. Our findings indicated that EA had a protective effect on TiO2 NP-exposed hepatocytes, reducing cytotoxicity, oxidative stress, and inflammation. Furthermore, EA treatment markedly reduced serum aminotransferase levels in mice exposed to TiO2 NPs. Furthermore, EA treatment notably reduced hepatic stress response, inflammation, and fibrosis in mice. The treatment of EA demonstrates non-inferiority compared to SFN. The protective effects of EA were attributed to the upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2), EA promoted the translocation and phosphorylation of Nrf2, as indicated by the finding that Nfe2l2 shRNA and inhibition of Nrf2 by ML385 reversed the EA-induced hepatoprotective effects in TiO2 NP-exposed hepatocytes and mice. CONCLUSION EA significantly mitigated liver injury induced by TiO2 NPs. Importantly, we identified that the nuclear translocation and phosphorylation of Nrf2 are the primary mechanisms through which EA alleviates liver injury resulting from exposure to TiO2 NPs. As a natural activator of Nrf2, EA emerges as a promising therapeutic candidate for treating TiO2 NPs-induced liver injury, further enhancing our understanding of its potential as a hepatoprotective agent and its underlying molecular mechanisms.
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Affiliation(s)
- Kunpeng Wang
- Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou University, Taizhou, Zhejiang Province, PR China; Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, PR China; General Surgery Laboratory, Renmin Hospital of Wuhan University, Wuhan, 318001, PR China
| | - Zhiqing Hao
- Department of Cell Biology, School of Medicine, Taizhou University, Taizhou, Zhejiang Province, 318001, PR China
| | - Jing Xie
- Department of Pathophysiology, School of Basic Medicine, Shenyang Medical College, Shenyang, Liaoning Province, 110000, PR China
| | - Liman Ma
- Department of Pathophysiology, School of Basic Medicine, Shenyang Medical College, Shenyang, Liaoning Province, 110000, PR China
| | - Weiwei Zhang
- Department of Cell Biology, School of Medicine, Taizhou University, Taizhou, Zhejiang Province, 318001, PR China
| | - Jinggang Mo
- Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou University, Taizhou, Zhejiang Province, PR China
| | - Lihua Li
- Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou University, Taizhou, Zhejiang Province, PR China.
| | - Chong Jin
- Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou University, Taizhou, Zhejiang Province, PR China.
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Summer M, Ashraf R, Ali S, Bach H, Noor S, Noor Q, Riaz S, Khan RRM. Inflammatory response of nanoparticles: Mechanisms, consequences, and strategies for mitigation. CHEMOSPHERE 2024; 363:142826. [PMID: 39002651 DOI: 10.1016/j.chemosphere.2024.142826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/11/2024] [Revised: 07/08/2024] [Accepted: 07/09/2024] [Indexed: 07/15/2024]
Abstract
Numerous nano-dimensioned materials have been generated as a result of several advancements in nanoscale science such as metallic nanoparticles (mNPs) which have aided in the advancement of related research. As a result, several significant nanoscale materials are being produced commercially. It is expected that in the future, products that are nanoscale, like mNPs, will be useful in daily life. Despite certain benefits, widespread use of metallic nanoparticles and nanotechnology has negative effects and puts human health at risk because of their continual accumulation in closed biological systems, along with their complex and diverse migratory and transformation pathways. Once within the human body, nanoparticles (NPs) disrupt the body's natural biological processes and trigger inflammatory responses. These NPs can also affect the immune system by activating separate pathways that either function independently or interact with one another. Cytotoxic effects, inflammatory response, genetic material damage, and mitochondrial dysfunction are among the consequences of mNPs. Oxidative stress and reactive oxygen species (ROS) generation caused by mNPs depend upon a multitude of factors that allow NPs to get inside cells and interact with biological macromolecules and cell organelles. This review focuses on how mNPs cause inflammation and oxidative stress, as well as disrupt cellular signaling pathways that support these effects. In addition, possibilities and problems to be reduced are addressed to improve future research on the creation of safer and more environmentally friendly metal-based nanoparticles for commercial acceptance and sustainable use in medicine and drug delivery.
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Affiliation(s)
- Muhammad Summer
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, Government College University, Lahore, 54000, Pakistan.
| | - Rimsha Ashraf
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, Government College University, Lahore, 54000, Pakistan
| | - Shaukat Ali
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, Government College University, Lahore, 54000, Pakistan
| | - Horacio Bach
- Department of Medicine, Division of Infectious Diseases, 2660 Oak Street, Vancouver, BC, V6H3Z6, Canada
| | - Shehzeen Noor
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, Government College University, Lahore, 54000, Pakistan
| | - Qudsia Noor
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, Government College University, Lahore, 54000, Pakistan
| | - Saima Riaz
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, Government College University, Lahore, 54000, Pakistan
| | - Rana Rashad Mahmood Khan
- Department of Chemistry, Government College University Lahore, Faculty of Chemistry and Life Sciences, Pakistan
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Bautista-Pérez R, Cano-Martínez A, Herrera-Rodríguez MA, Ramos-Godinez MDP, Pérez Reyes OL, Chirino YI, Rodríguez Serrano ZJ, López-Marure R. Oral Exposure to Titanium Dioxide E171 and Zinc Oxide Nanoparticles Induces Multi-Organ Damage in Rats: Role of Ceramide. Int J Mol Sci 2024; 25:5881. [PMID: 38892068 PMCID: PMC11172338 DOI: 10.3390/ijms25115881] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Revised: 05/22/2024] [Accepted: 05/23/2024] [Indexed: 06/21/2024] Open
Abstract
Food-grade titanium dioxide (E171) and zinc oxide nanoparticles (ZnO NPs) are common food additives for human consumption. We examined multi-organ toxicity of both compounds on Wistar rats orally exposed for 90 days. Rats were divided into three groups: (1) control (saline solution), (2) E171-exposed, and (3) ZnO NPs-exposed. Histological examination was performed with hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM). Ceramide (Cer), 3-nitrotyrosine (NT), and lysosome-associated membrane protein 2 (LAMP-2) were detected by immunofluorescence. Relevant histological changes were observed: disorganization, inflammatory cell infiltration, and mitochondrial damage. Increased levels of Cer, NT, and LAMP-2 were observed in the liver, kidney, and brain of E171- and ZnO NPs-exposed rats, and in rat hearts exposed to ZnO NPs. E171 up-regulated Cer and NT levels in the aorta and heart, while ZnO NPs up-regulated them in the aorta. Both NPs increased LAMP-2 expression in the intestine. In conclusion, chronic oral exposure to metallic NPs causes multi-organ injury, reflecting how these food additives pose a threat to human health. Our results suggest how complex interplay between ROS, Cer, LAMP-2, and NT may modulate organ function during NP damage.
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Affiliation(s)
- Rocío Bautista-Pérez
- Departamento de Biología Molecular, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, Mexico;
| | - Agustina Cano-Martínez
- Departamento de Fisiología, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, Mexico; (A.C.-M.)
| | | | | | - Olga Lidia Pérez Reyes
- Departamento de Patología, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, Mexico
| | - Yolanda Irasema Chirino
- Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Mexico City 54090, Mexico
| | - Zariá José Rodríguez Serrano
- Departamento de Fisiología, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, Mexico; (A.C.-M.)
| | - Rebeca López-Marure
- Departamento de Fisiología, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, Mexico; (A.C.-M.)
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Das SK, Sen K, Ghosh B, Ghosh N, Sinha K, Sil PC. Molecular mechanism of nanomaterials induced liver injury: A review. World J Hepatol 2024; 16:566-600. [PMID: 38689743 PMCID: PMC11056894 DOI: 10.4254/wjh.v16.i4.566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 02/05/2024] [Accepted: 03/19/2024] [Indexed: 04/24/2024] Open
Abstract
The unique physicochemical properties inherent to nanoscale materials have unveiled numerous potential applications, spanning beyond the pharmaceutical and medical sectors into various consumer industries like food and cosmetics. Consequently, humans encounter nanomaterials through diverse exposure routes, giving rise to potential health considerations. Noteworthy among these materials are silica and specific metallic nanoparticles, extensively utilized in consumer products, which have garnered substantial attention due to their propensity to accumulate and induce adverse effects in the liver. This review paper aims to provide an exhaustive examination of the molecular mechanisms underpinning nanomaterial-induced hepatotoxicity, drawing insights from both in vitro and in vivo studies. Primarily, the most frequently observed manifestations of toxicity following the exposure of cells or animal models to various nanomaterials involve the initiation of oxidative stress and inflammation. Additionally, we delve into the existing in vitro models employed for evaluating the hepatotoxic effects of nanomaterials, emphasizing the persistent endeavors to advance and bolster the reliability of these models for nanotoxicology research.
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Affiliation(s)
- Sanjib Kumar Das
- Department of Zoology, Jhargram Raj College, Jhargram 721507, India
| | - Koushik Sen
- Department of Zoology, Jhargram Raj College, Jhargram 721507, India
| | - Biswatosh Ghosh
- Department of Zoology, Bidhannagar College, Kolkata 700064, India
| | - Nabanita Ghosh
- Department of Zoology, Maulana Azad College, Kolkata 700013, India
| | - Krishnendu Sinha
- Department of Zoology, Jhargram Raj College, Jhargram 721507, India.
| | - Parames C Sil
- Department of Molecular Medicine, Bose Institute, Calcutta 700054, India
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10
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Li C, Tang M. The toxicological effects of nano titanium dioxide on target organs and mechanisms of toxicity. J Appl Toxicol 2024; 44:152-164. [PMID: 37655586 DOI: 10.1002/jat.4534] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Revised: 08/04/2023] [Accepted: 08/13/2023] [Indexed: 09/02/2023]
Abstract
Nano-titanium dioxide (TiO2 NPs) is widely used for its extremely high stability, corrosion resistance, and photocatalytic properties and has penetrated into various fields of production and life. Assessing its toxicity to different organs should be a key part of preclinical toxicity assessment of TiO2 NPs, which is relatively incomprehensive yet. Therefore, this review focuses on the toxic effects of TiO2 NPs on various organs in mammals and biological mechanisms from different organs. The commonality of toxic effects on various target organs reflected in tissue structure damage and dysfunction, such as liver damage and dysfunction; pulmonary fibrosis; and renal impairment (including hematuria and nephritis); damage of brain tissue and neurons; alteration of intestinal villi; and weight loss. And effects on the reproductive system are affected by different sexes, including ovarian dysfunction, testicular development damage, and sperm viability reduction. We believe that the toxic mechanisms of TiO2 NPs in target organs have commonalities, such as oxidative stress, inflammatory responses, and organelle damage. However, different target organ toxicities also have their specificities. TiO2 NPs disturb the intestinal flora and cause undesirable changes in feces products. And in spleen are infiltration of neutrophils and lymphadenopathy and eventually immune deficiency. Although the toxic pathways are different, but there may be a close link between the different toxic pathways. In this article, the main manifestations of the toxic effects of titanium dioxide nanoparticles on major mammalian organs are reviewed, in order to provide basic data for their better application from a medical perspective.
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Affiliation(s)
- Congcong Li
- Key Laboratory of Environmental Medicine of Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, People's Republic of China
| | - Meng Tang
- Key Laboratory of Environmental Medicine of Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, People's Republic of China
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11
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Mao J, Tan L, Tian C, Wang W, Zhang H, Zhu Z, Li Y. Research progress on rodent models and its mechanisms of liver injury. Life Sci 2024; 337:122343. [PMID: 38104860 DOI: 10.1016/j.lfs.2023.122343] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Revised: 11/22/2023] [Accepted: 12/06/2023] [Indexed: 12/19/2023]
Abstract
The liver is the most important organ for biological transformation in the body and is crucial for maintaining the body's vital activities. Liver injury is a serious pathological condition that is commonly found in many liver diseases. It has a high incidence rate, is difficult to cure, and is prone to recurrence. Liver injury can cause serious harm to the body, ranging from mild to severe fatty liver disease. If the condition continues to worsen, it can lead to liver fibrosis and cirrhosis, ultimately resulting in liver failure or liver cancer, which can seriously endanger human life and health. Therefore, establishing an rodent model that mimics the pathogenesis and severity of clinical liver injury is of great significance for better understanding the pathogenesis of liver injury patients and developing more effective clinical treatment methods. The author of this article summarizes common chemical liver injury models, immune liver injury models, alcoholic liver injury models, drug-induced liver injury models, and systematically elaborates on the modeling methods, mechanisms of action, pathways of action, and advantages or disadvantages of each type of model. The aim of this study is to establish reliable rodent models for researchers to use in exploring anti-liver injury and hepatoprotective drugs. By creating more accurate theoretical frameworks, we hope to provide new insights into the treatment of clinical liver injury diseases.
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Affiliation(s)
- Jingxin Mao
- Chongqing Medical and Pharmaceutical College, Chongqing 400030, China; College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China
| | - Lihong Tan
- Chongqing Medical and Pharmaceutical College, Chongqing 400030, China; Chongqing Key Laboratory of High Active Traditional Chinese Drug Delivery System, Chongqing 400030, China
| | - Cheng Tian
- Chongqing Medical and Pharmaceutical College, Chongqing 400030, China; Chongqing Key Laboratory of High Active Traditional Chinese Drug Delivery System, Chongqing 400030, China
| | - Wenxiang Wang
- Chongqing Three Gorges Medical College, Chongqing 404120, China
| | - Hao Zhang
- Chongqing Medical and Pharmaceutical College, Chongqing 400030, China; Chongqing Key Laboratory of High Active Traditional Chinese Drug Delivery System, Chongqing 400030, China
| | - Zhaojing Zhu
- Chongqing Medical and Pharmaceutical College, Chongqing 400030, China; Chongqing Key Laboratory of High Active Traditional Chinese Drug Delivery System, Chongqing 400030, China
| | - Yan Li
- Chongqing Medical and Pharmaceutical College, Chongqing 400030, China; Chongqing Key Laboratory of High Active Traditional Chinese Drug Delivery System, Chongqing 400030, China.
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12
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Singh S, Sharma K, Sharma H. Green Extracts with Metal-based Nanoparticles for Treating Inflammatory Diseases: A Review. Curr Drug Deliv 2024; 21:544-570. [PMID: 37278036 DOI: 10.2174/1567201820666230602164325] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2023] [Revised: 04/24/2023] [Accepted: 05/04/2023] [Indexed: 06/07/2023]
Abstract
Globally, high death rates and poor quality of life are caused mainly by inflammatory diseases. Corticosteroids, which may have systemic side effects and would enhance the risk of infection, are the common forms of therapy. The field of nanomedicine has created composite nanoparticles that carry a pharmacological carrier and target ligands for distribution to sites of inflammation with less systemic toxicity. However, their relatively large size often causes systemic clearance. An interesting approach is metal-based nanoparticles that naturally reduce inflammation. They are made not only to be small enough to pass through biological barriers but also to allow label-free monitoring of their interactions with cells. The following literature review discusses the mechanistic analysis of the anti-inflammatory properties of several metal-based nanoparticles, including gold, silver, titanium dioxide, selenium, and zinc oxide. Current research focuses on the mechanisms by which nanoparticles infiltrate cells and the anti-inflammatory techniques using herbal extracts-based nanoparticles. Additionally, it provides a brief overview of the literature on many environmentally friendly sources employed in nanoparticle production and the mechanisms of action of various nanoparticles.
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Affiliation(s)
- Sonia Singh
- Institute of Pharmaceutical Research GLA University, 17km Stone, NH-2, Mathura-Delhi Road Mathura, Chaumuhan, Uttar Pradesh-281406, India
| | - Khushi Sharma
- Institute of Pharmaceutical Research GLA University, 17km Stone, NH-2, Mathura-Delhi Road Mathura, Chaumuhan, Uttar Pradesh-281406, India
| | - Himanshu Sharma
- Department of Computer Engineering & Applications GLA University, 17km Stone, NH-2, Mathura-Delhi Road Mathura, Chaumuhan, Uttar Pradesh-281406, India
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13
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Ryabtseva MS, Umanskaya SF, Shevchenko MA, Krivobok VS, Kolobov AV, Nastulyavichus AA, Chentsov SI, Sibirtsev VD. Transformation of Nano-Size Titanium Dioxide Particles in the Gastrointestinal Tract and Its Role in the Transfer of Nanoparticles through the Intestinal Barrier. Int J Mol Sci 2023; 24:14911. [PMID: 37834359 PMCID: PMC10573324 DOI: 10.3390/ijms241914911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2023] [Revised: 09/27/2023] [Accepted: 10/02/2023] [Indexed: 10/15/2023] Open
Abstract
In this work, the size transformation of the TiO2 nanofraction from pharmaceutical grade E171 powder was studied during its transit through the gastrointestinal tract (GIT). It was shown that pharmaceutical-grade TiO2 powder contained about 0.68% (w/w) of particles smaller than 240 nm in diameter. In the observed GIT transit process the TiO2 nanoparticles were agglomerated up to 150-200 nm in simulated salivary fluid, with gradual agglomerate enlargement up to 300-600 nm and more than 1 micron in simulated gastric fluid. In the intestinal fluid the reverse process occurred, involving a decrease of agglomerates accompanied by the formation of a small fraction with ~50 nm average size. This fraction can be further involved in the histohematic transport process. The acidity degree (pH) and mineral composition of solutions, as well as the transit speed along the gastrointestinal tract, influence the nature of the particle transformation significantly. The rapid passing between the gastrointestinal tract sections creates conditions for a decrease in part of the TiO2 particles, up to 100 nm, and may be associated with the violation of the structural and functional integrity of the intestinal mucus layer.
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Affiliation(s)
- M. S. Ryabtseva
- P. N. Lebedev Physical Institute, Russian Academy of Sciences, Leninsky Prospect 53, Moscow 119991, Russia; (S.F.U.); (M.A.S.); (V.S.K.); (A.V.K.); (A.A.N.); (S.I.C.)
| | - S. F. Umanskaya
- P. N. Lebedev Physical Institute, Russian Academy of Sciences, Leninsky Prospect 53, Moscow 119991, Russia; (S.F.U.); (M.A.S.); (V.S.K.); (A.V.K.); (A.A.N.); (S.I.C.)
| | - M. A. Shevchenko
- P. N. Lebedev Physical Institute, Russian Academy of Sciences, Leninsky Prospect 53, Moscow 119991, Russia; (S.F.U.); (M.A.S.); (V.S.K.); (A.V.K.); (A.A.N.); (S.I.C.)
| | - V. S. Krivobok
- P. N. Lebedev Physical Institute, Russian Academy of Sciences, Leninsky Prospect 53, Moscow 119991, Russia; (S.F.U.); (M.A.S.); (V.S.K.); (A.V.K.); (A.A.N.); (S.I.C.)
| | - A. V. Kolobov
- P. N. Lebedev Physical Institute, Russian Academy of Sciences, Leninsky Prospect 53, Moscow 119991, Russia; (S.F.U.); (M.A.S.); (V.S.K.); (A.V.K.); (A.A.N.); (S.I.C.)
| | - A. A. Nastulyavichus
- P. N. Lebedev Physical Institute, Russian Academy of Sciences, Leninsky Prospect 53, Moscow 119991, Russia; (S.F.U.); (M.A.S.); (V.S.K.); (A.V.K.); (A.A.N.); (S.I.C.)
| | - S. I. Chentsov
- P. N. Lebedev Physical Institute, Russian Academy of Sciences, Leninsky Prospect 53, Moscow 119991, Russia; (S.F.U.); (M.A.S.); (V.S.K.); (A.V.K.); (A.A.N.); (S.I.C.)
| | - V. D. Sibirtsev
- Department of Veterinary Medicine, Institute of Veterinary, Veterinary-Sanitary Examination and Agricultural Safety, Russian Biotechnological University, Volokolamskoe Highway 11, Moscow 125080, Russia;
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14
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Fonseca E, Vázquez M, Rodriguez-Lorenzo L, Mallo N, Pinheiro I, Sousa ML, Cabaleiro S, Quarato M, Spuch-Calvar M, Correa-Duarte MA, López-Mayán JJ, Mackey M, Moreda A, Vasconcelos V, Espiña B, Campos A, Araújo MJ. Getting fat and stressed: Effects of dietary intake of titanium dioxide nanoparticles in the liver of turbot Scophthalmus maximus. JOURNAL OF HAZARDOUS MATERIALS 2023; 458:131915. [PMID: 37413800 DOI: 10.1016/j.jhazmat.2023.131915] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 06/12/2023] [Accepted: 06/21/2023] [Indexed: 07/08/2023]
Abstract
The extensive use of nanomaterials, including titanium dioxide nanoparticles (TiO2 NPs), raises concerns about their persistence in ecosystems. Protecting aquatic ecosystems and ensuring healthy and safe aquaculture products requires the assessment of the potential impacts of NPs on organisms. Here, we study the effects of a sublethal concentration of citrate-coated TiO2 NPs of two different primary sizes over time in flatfish turbot, Scophthalmus maximus (Linnaeus, 1758). Bioaccumulation, histology and gene expression were assessed in the liver to address morphophysiological responses to citrate-coated TiO2 NPs. Our analyses demonstrated a variable abundance of lipid droplets (LDs) in hepatocytes dependent on TiO2 NPs size, an increase in turbot exposed to smaller TiO2 NPs and a depletion with larger TiO2 NPs. The expression patterns of genes related to oxidative and immune responses and lipid metabolism (nrf2, nfκb1, and cpt1a) were dependent on the presence of TiO2 NPs and time of exposure supporting the variance in hepatic LDs distribution over time with the different NPs. The citrate coating is proposed as the likely catalyst for such effects. Thus, our findings highlight the need to scrutinize the risks associated with exposure to NPs with distinct properties, such as primary size, coatings, and crystalline forms, in aquatic organisms.
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Affiliation(s)
- Elza Fonseca
- CIIMAR - Interdisciplinary Centre of Marine and Environmental Research, Terminal de Cruzeiros do Porto de Leixões, Av. General Norton de Matos s/n, 4450-208 Matosinhos, Portugal.
| | - María Vázquez
- CETGA - Centro Técnológico del Cluster de la Acuicultura, Punta de Couso s/n, 15965 Ribeira, A Coruña, Spain
| | - Laura Rodriguez-Lorenzo
- INL - International Iberian Nanotechnology Laboratory, Av. Mestre José Veiga s/n, 4715-330 Braga, Portugal
| | - Natalia Mallo
- CETGA - Centro Técnológico del Cluster de la Acuicultura, Punta de Couso s/n, 15965 Ribeira, A Coruña, Spain
| | - Ivone Pinheiro
- INL - International Iberian Nanotechnology Laboratory, Av. Mestre José Veiga s/n, 4715-330 Braga, Portugal
| | - Maria Lígia Sousa
- CIIMAR - Interdisciplinary Centre of Marine and Environmental Research, Terminal de Cruzeiros do Porto de Leixões, Av. General Norton de Matos s/n, 4450-208 Matosinhos, Portugal
| | - Santiago Cabaleiro
- CETGA - Centro Técnológico del Cluster de la Acuicultura, Punta de Couso s/n, 15965 Ribeira, A Coruña, Spain
| | - Monica Quarato
- INL - International Iberian Nanotechnology Laboratory, Av. Mestre José Veiga s/n, 4715-330 Braga, Portugal
| | - Miguel Spuch-Calvar
- CINBIO - Centro de Investigación en Nanomateriais e Biomedicina, Universidade de Vigo, 36310 Vigo, Spain
| | - Miguel A Correa-Duarte
- CINBIO - Centro de Investigación en Nanomateriais e Biomedicina, Universidade de Vigo, 36310 Vigo, Spain
| | - Juan José López-Mayán
- GETEE - Trace Element, Spectroscopy and Speciation Group, Institute de Materiais iMATUS. Faculty of Chemistry, University of Santiago de Compostela, Av. das Ciencias s/n, 15782 Santiago de Compostela, Spain
| | - Mick Mackey
- IRMRC - Indigo Rock Marine Research Centre, Gearhies, Bantry, Co., Cork P75 AX07, Ireland
| | - Antonio Moreda
- GETEE - Trace Element, Spectroscopy and Speciation Group, Institute de Materiais iMATUS. Faculty of Chemistry, University of Santiago de Compostela, Av. das Ciencias s/n, 15782 Santiago de Compostela, Spain
| | - Vítor Vasconcelos
- CIIMAR - Interdisciplinary Centre of Marine and Environmental Research, Terminal de Cruzeiros do Porto de Leixões, Av. General Norton de Matos s/n, 4450-208 Matosinhos, Portugal; FCUP - Faculty of Sciences, University of Porto, Biology Department, Rua do Campo Alegre s/n, 4169-007 Porto, Portugal
| | - Begoña Espiña
- INL - International Iberian Nanotechnology Laboratory, Av. Mestre José Veiga s/n, 4715-330 Braga, Portugal
| | - Alexandre Campos
- CIIMAR - Interdisciplinary Centre of Marine and Environmental Research, Terminal de Cruzeiros do Porto de Leixões, Av. General Norton de Matos s/n, 4450-208 Matosinhos, Portugal
| | - Mário Jorge Araújo
- CIIMAR - Interdisciplinary Centre of Marine and Environmental Research, Terminal de Cruzeiros do Porto de Leixões, Av. General Norton de Matos s/n, 4450-208 Matosinhos, Portugal
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15
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Parveen N, Akbarsha MA, Latif Wani AB, Ansari MO, Ahmad MF, Shadab GGHA. Protective effect of quercetin and thymoquinone against genotoxicity and oxidative stress induced by ZnO nanoparticles in the Wistar rat model. MUTATION RESEARCH. GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS 2023; 890:503661. [PMID: 37567646 DOI: 10.1016/j.mrgentox.2023.503661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 07/13/2023] [Accepted: 07/19/2023] [Indexed: 08/13/2023]
Abstract
Zinc oxide nanoparticles (ZnO-NPs) are increasingly used in a variety of consumer and other commercial products. Hence, man faces the risk of exposure to ZnO-NPs and the consequent adverse health effects. Mitigation/prevention of such effects using natural products has drawn the attention of scientists. Therefore, the aim of the present study has been to find the toxic effects associated with exposure to ZnO-NPs, and the protective role of the phytochemicals thymoquinone (TQ) and quercetin (QCT) in the rat model. ZnO-NPs were administered to male Wistar rats through oral route; TQ / QCT was concurrently administered through intra-peritoneal route. The response in the animal was analyzed adopting chromosomal aberration test, micronucleus test, and comet assay of bone marrow cells to assess the genotoxicity, and biochemical assays of superoxide dismutase (SOD), catalase (CAT), lipid peroxidation (LPO), total extractable protein of liver, and reduced glutathione (GSH) of liver homogenate to monitor the changes in the antioxidant defense mechanism in response to the oxidative stress. Treatment of 300 mg/kg body weight (bw) of ZnO-NPs produced adverse effects on all aspects analyzed viz., structural chromosomal aberrations, micronuclei formation, DNA damage, SOD, catalase, lipid peroxidation, GSH, and extractable total protein of liver. Co-treatment of TQ / QCT offered protection against the toxicity induced by ZnO-NPs. The most optimum doses of TQ and QCT that offered the best protection were 18 mg/kg bw and 500 mg/kg bw, respectively. The study reveals that TQ / QCT supplementation is beneficial in the context of toxic effects of ZnO-NPs.
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Affiliation(s)
- Nuzhat Parveen
- Cytogenetics and Molecular Toxicology Lab., Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh 202002, Uttar Pradesh, India.
| | | | - A B Latif Wani
- Cytogenetics and Molecular Toxicology Lab., Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh 202002, Uttar Pradesh, India
| | - Mohd Owais Ansari
- Cytogenetics and Molecular Toxicology Lab., Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh 202002, Uttar Pradesh, India
| | - Md Fahim Ahmad
- Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, Uttar Pradesh, India
| | - G G H A Shadab
- Cytogenetics and Molecular Toxicology Lab., Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh 202002, Uttar Pradesh, India
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16
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Abdel Aal SM, Mohammed MZ, Abdelrahman AA, Samy W, Abdelaal GMM, Deraz RH, Abdelrahman SA. Histological and biochemical evaluation of the effects of silver nanoparticles (AgNps) versus titanium dioxide nanoparticles (TiO 2NPs) on rat parotid gland. Ultrastruct Pathol 2023; 47:339-363. [PMID: 37132546 DOI: 10.1080/01913123.2023.2205924] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 04/04/2023] [Accepted: 04/19/2023] [Indexed: 05/04/2023]
Abstract
The unlimited use of nanoparticles (NPs) results in toxic impacts on different tissues. The current study aimed to compare the adverse effects of AgNPs and TiO2NPs on the parotid gland of adult male albino rats as regards the histopathological, immunohistochemical, and biochemical changes, exploring the possible underlying mechanisms and the degree of improvement after cessation of administration. Fifty-four adult male albino rats were divided into control group (I), AgNPs-injected group (II), and TiO2NPs-injected group (III). We measured the levels of tumor necrosis factor-alpha (TNF-α) and interleukin (IL-6) in the serum, and levels of MDA and GSH in parotid tissue homogenate. Quantitative real-time polymerase-chain reaction (qRT-PCR) was used to measure the expression levels of peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC1-α), nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), mouse double minute 2 (MDM2), Caspase-3 Col1a1, and Occludin. Parotid tissue sections were examined by light microscope (Hematoxylin & Eosin and Mallory trichrome stains), electron microscope, and immunohistochemical examination of CD68 and anti-caspase-3 antibodies. Both NPs severely affected the acinar cells and damaged the tight junction between them by enhancing expression of the inflammatory cytokines, inducing oxidative stress, and disturbing the expression levels of the studied genes. They also stimulated fibrosis, acinar cell apoptosis, and inflammatory cells infiltration in parotid tissue. TiO2NPs effects were less severe than AgNPs. Cessation of exposure to both NPs, ameliorated the biochemical and structural findings with more improvement in TiO2NPs withdrawal. In conclusion: AgNPs and TiO2NPs adversely affected the parotid gland, but TiO2NPs were less toxic than AgNPs.
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Affiliation(s)
- Sara M Abdel Aal
- Medical Histology & Cell Biology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Maha Z Mohammed
- Medical Histology & Cell Biology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Abeer A Abdelrahman
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Walaa Samy
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Ghadeer M M Abdelaal
- Forensic Medicine & Clinical Toxicology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Raghda H Deraz
- Forensic Medicine & Clinical Toxicology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Shaimaa A Abdelrahman
- Medical Histology & Cell Biology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
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17
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Almomen A, Alsaleh NB, El-Toni AM, EL-Mahrouky MA, Alhowyan AA, Alkholief M, Alshamsan A, Khurana N, Ghandehari H. In Vitro Safety Assessment of In-House Synthesized Titanium Dioxide Nanoparticles: Impact of Washing and Temperature Conditions. Int J Mol Sci 2023; 24:9966. [PMID: 37373112 PMCID: PMC10298741 DOI: 10.3390/ijms24129966] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Revised: 06/07/2023] [Accepted: 06/07/2023] [Indexed: 06/29/2023] Open
Abstract
Titanium dioxide nanoparticles (TiO2 NPs) have been widely used in food, cosmetics, and biomedical research. However, human safety following exposure to TiO2 NPs remains to be fully understood. The aim of this study was to evaluate the in vitro safety and toxicity of TiO2 NPs synthesized via the Stöber method under different washing and temperature conditions. TiO2 NPs were characterized by their size, shape, surface charge, surface area, crystalline pattern, and band gap. Biological studies were conducted on phagocytic (RAW 264.7) and non-phagocytic (HEK-239) cells. Results showed that washing amorphous as-prepared TiO2 NPs (T1) with ethanol while applying heat at 550 °C (T2) resulted in a reduction in the surface area and charge compared to washing with water (T3) or a higher temperature (800 °C) (T4) and influenced the formation of crystalline structures with the anatase phase in T2 and T3 and rutile/anatase mixture in T4. Biological and toxicological responses varied among TiO2 NPs. T1 was associated with significant cellular internalization and toxicity in both cell types compared to other TiO2 NPs. Furthermore, the formation of the crystalline structure induced toxicity independent of other physicochemical properties. Compared with anatase, the rutile phase (T4) reduced cellular internalization and toxicity. However, comparable levels of reactive oxygen species were generated following exposure to the different types of TiO2, indicating that toxicity is partially driven via non-oxidative pathways. TiO2 NPs were able to trigger an inflammatory response, with varying trends among the two tested cell types. Together, the findings emphasize the importance of standardizing engineered nanomaterial synthesis conditions and evaluating the associated biological and toxicological consequences arising from changes in synthesis conditions.
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Affiliation(s)
- Aliyah Almomen
- Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11491, Saudi Arabia
| | - Nasser B. Alsaleh
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia;
| | - Ahmed Mohamed El-Toni
- King Abdullah Institute for Nanotechnology, King Saud University, Riyadh 11451, Saudi Arabia;
- Nanomaterials and Nanotechnology Department, Central Metallurgical Research and Development Institute (CMRDI), Cairo 11421, Egypt
| | - Mohamed A. EL-Mahrouky
- Soil Science Department, College of Food and Agriculture Science, King Saud University, Riyadh 11451, Saudi Arabia
| | - Adel Ali Alhowyan
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; (A.A.A.); (M.A.)
| | - Musaed Alkholief
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; (A.A.A.); (M.A.)
| | - Aws Alshamsan
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; (A.A.A.); (M.A.)
| | - Nitish Khurana
- Department of Molecular Pharmaceutics, University of Utah, Salt Lake City, UT 84112, USA (H.G.)
- Utah Center for Nanomedicine, University of Utah, Salt Lake City, UT 84112, USA
| | - Hamidreza Ghandehari
- Department of Molecular Pharmaceutics, University of Utah, Salt Lake City, UT 84112, USA (H.G.)
- Utah Center for Nanomedicine, University of Utah, Salt Lake City, UT 84112, USA
- Department of Biomedical Engineering, University of Utah, Salt Lake City, UT 84112, USA
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18
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Shahmoradi SS, Salehzadeh A, Ranji N, Habibollahi H. Trigger of apoptosis in human liver cancer cell line (HepG2) by titanium dioxide nanoparticles functionalized by glutamine and conjugated with thiosemicarbazone. 3 Biotech 2023; 13:195. [PMID: 37206358 PMCID: PMC10188684 DOI: 10.1007/s13205-023-03609-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Accepted: 05/03/2023] [Indexed: 05/21/2023] Open
Abstract
The incidence of liver cancer, the third cause of cancer-associated death, has been growing, worldwide. The increasing trend of liver cancer incidence and mortality indicates the inefficiency of current therapeutic approaches, especially anticancer chemotherapy. Owing to the promising anticancer potential of Thiosemicarbazone (TSC) complexes, this work was conducted to synthesize titanium oxide nanoparticles conjugated with TSC through glutamine functionalization (TiO2@Gln-TSC NPs) and characterize their anticancer mechanism in HepG2 liver cancer cells. Physicochemical analyses of the synthesized particles, including FT-IR, XRD, SEM, TEM, Zeta potential and DLS, and EDS-mapping confirmed the proper synthesis and conjugation of TiO2@Gln-TSC NPs. The synthesized NPs were almost spherical, with a size range of 10-80 nm, a zeta potential of - 57.8 mV, a hydrodynamic size of 127 nm, and without impurities. Investigation of the cytotoxic effect of TiO2@Gln-TSC in HepG2 and HEK293 human normal cells indicated significantly higher toxicity in cancer cells (IC50 = 75 µg/mL) than normal cells (IC50 = 210 µg/mL). Flow cytometry analysis of TiO2@Gln-TSC treated and control cells showed that the population of apoptotic cells considerably increased from 2.8 to 27.3% after treatment with the NPs. Moreover, 34.1% of the TiO2@Gln-TSC treated cells were mainly arrested at the sub-G1 phase of the cell cycle, which was significantly greater than control cells (8.4%). The Hoechst staining assay showed considerable nuclear damage, including chromatin fragmentation and the appearance of apoptotic bodies. This work introduced TiO2@Gln-TSC NPs as a promising anticancer compound that could combat liver cancer cells through apoptosis induction.
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Affiliation(s)
| | - Ali Salehzadeh
- Department of Biology, Rasht Branch, Islamic Azad University, Rasht, Iran
| | - Najmeh Ranji
- Department of Biology, Rasht Branch, Islamic Azad University, Rasht, Iran
| | - Hadi Habibollahi
- Department of Biology, Rasht Branch, Islamic Azad University, Rasht, Iran
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19
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Gomes SIL, Roca CP, Pokhrel S, Mädler L, Scott-Fordsmand JJ, Amorim MJB. TiO 2 nanoparticles' library toxicity (UV and non-UV exposure) - High-throughput in vivo transcriptomics reveals mechanisms. NANOIMPACT 2023; 30:100458. [PMID: 36858316 DOI: 10.1016/j.impact.2023.100458] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 02/21/2023] [Accepted: 02/24/2023] [Indexed: 06/03/2023]
Abstract
The hazards of nanomaterials/nanoparticles (NMs/NPs) are mostly assessed using individual NMs, and a more systematic approach, using many NMs, is needed to evaluate its risks in the environment. Libraries of NMs, with a range of identified different but related characters/descriptors allow the comparison of effects across many NMs. The effects of a custom designed Fe-doped TiO2 NMs library containing 11 NMs was assessed on the soil model Enchytraeus crypticus (Oligochaeta), both with and without UV (standard fluorescent) radiation. Effects were analyzed at organism (phenotypic, survival and reproduction) and gene expression level (transcriptomics, high-throughput 4x44K microarray) to understand the underlying mechanisms. A total of 48 microarrays (20 test conditions) were done plus controls (UV and non-UV). Unique mechanisms induced by TiO2 NPs exposure included the impairment in RNA processing for TiO2_10nm, or deregulated apoptosis for 2%FeTiO2_10nm. Strikingly apparent was the size dependent effects such as induction of reproductive effects via smaller TiO2 NPs (≤12 nm) - embryo interaction, while larger particles (27 nm) caused reproductive effects through different mechanisms. Also, phagocytosis was affected by 12 and 27 nm NPs, but not by ≤11 nm. The organism level study shows the integrated response, i.e. the result after a cascade of events. While uni-cell models offer key mechanistic information, we here deliver a combined biological system level (phenotype and genotype), seldom available, especially for environmental models.
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Affiliation(s)
- Susana I L Gomes
- Department of Biology & CESAM, University of Aveiro, 3810-193 Aveiro, Portugal
| | - Carlos P Roca
- Department of Ecoscience, Aarhus University, C.F. Møllers Alle 4, DK-8000, Aarhus, Denmark
| | - Suman Pokhrel
- Department of Production Engineering, University of Bremen, Badgasteiner Str. 1, 28359 Bremen, Germany; Leibniz Institute for Materials Engineering IWT, Badgasteiner Str. 3, 28359 Bremen, Germany
| | - Lutz Mädler
- Department of Production Engineering, University of Bremen, Badgasteiner Str. 1, 28359 Bremen, Germany; Leibniz Institute for Materials Engineering IWT, Badgasteiner Str. 3, 28359 Bremen, Germany
| | | | - Mónica J B Amorim
- Department of Biology & CESAM, University of Aveiro, 3810-193 Aveiro, Portugal.
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20
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Bhattacharjee R, Negi A, Bhattacharya B, Dey T, Mitra P, Preetam S, Kumar L, Kar S, Das SS, Iqbal D, Kamal M, Alghofaili F, Malik S, Dey A, Jha SK, Ojha S, Paiva-Santos AC, Kesari KK, Jha NK. Nanotheranostics to Target Antibiotic-resistant Bacteria: Strategies and Applications. OPENNANO 2023. [DOI: 10.1016/j.onano.2023.100138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/07/2023]
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21
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Aljabali AA, Obeid MA, Bashatwah RM, Serrano-Aroca Á, Mishra V, Mishra Y, El-Tanani M, Hromić-Jahjefendić A, Kapoor DN, Goyal R, Naikoo GA, Tambuwala MM. Nanomaterials and Their Impact on the Immune System. Int J Mol Sci 2023; 24:2008. [PMID: 36768330 PMCID: PMC9917130 DOI: 10.3390/ijms24032008] [Citation(s) in RCA: 56] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 01/05/2023] [Accepted: 01/13/2023] [Indexed: 01/20/2023] Open
Abstract
Nanomaterials have been the focus of intensive development and research in the medical and industrial sectors over the past several decades. Some studies have found that these compounds can have a detrimental impact on living organisms, including their cellular components. Despite the obvious advantages of using nanomaterials in a wide range of applications, there is sometimes skepticism caused by the lack of substantial proof that evaluates potential toxicities. The interactions of nanoparticles (NPs) with cells of the immune system and their biomolecule pathways are an area of interest for researchers. It is possible to modify NPs so that they are not recognized by the immune system or so that they suppress or stimulate the immune system in a targeted manner. In this review, we look at the literature on nanomaterials for immunostimulation and immunosuppression and their impact on how changing the physicochemical features of the particles could alter their interactions with immune cells for the better or for the worse (immunotoxicity). We also look into whether the NPs have a unique or unexpected (but desired) effect on the immune system, and whether the surface grafting of polymers or surface coatings makes stealth nanomaterials that the immune system cannot find and get rid of.
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Affiliation(s)
- Alaa A. Aljabali
- Faculty of Pharmacy, Department of Pharmaceutics and Pharmaceutical Technology, Yarmouk University, P.O. Box 566, Irbid 21163, Jordan
| | - Mohammad A. Obeid
- Faculty of Pharmacy, Department of Pharmaceutics and Pharmaceutical Technology, Yarmouk University, P.O. Box 566, Irbid 21163, Jordan
| | - Rasha M. Bashatwah
- Faculty of Pharmacy, Department of Pharmaceutics and Pharmaceutical Technology, Yarmouk University, P.O. Box 566, Irbid 21163, Jordan
| | - Ángel Serrano-Aroca
- Biomaterials and Bioengineering Lab., Centro de Investigación Traslacional San Alberto Magno, Universidad Católica de Valencia, San Vicente Mártir, 46001 Valencia, Spain
| | - Vijay Mishra
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, Punjab, India
| | - Yachana Mishra
- Department of Zoology, School of Bioengineering and Bioscience, Lovely Professional University, Phagwara 144411, Punjab, India
| | - Mohamed El-Tanani
- Pharmacological and Diagnostic Research Centre, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 19328, Jordan
| | - Altijana Hromić-Jahjefendić
- Department of Genetics and Bioengineering, Faculty of Engineering and Natural Sciences, International University of Sarajevo, Hrasnicka Cesta 15, 71000 Sarajevo, Bosnia and Herzegovina
| | - Deepak N. Kapoor
- School of Pharmaceutical Sciences, Shoolini University of Biotechnology and Management Sciences, Solan 173229, Himachal Pradesh, India
| | - Rohit Goyal
- School of Pharmaceutical Sciences, Shoolini University of Biotechnology and Management Sciences, Solan 173229, Himachal Pradesh, India
| | - Gowhar A. Naikoo
- Department of Mathematics and Sciences, College of Arts and Applied Sciences, Dhofar University, Salalah PC 211, Oman
| | - Murtaza M. Tambuwala
- Lincoln Medical School, University of Lincoln, Brayford Pool Campus, Lincoln LN6 7TS, UK
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22
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Mohammadparast V, Mallard BL. The effect and underlying mechanisms of titanium dioxide nanoparticles on glucose homeostasis: A literature review. J Appl Toxicol 2023; 43:22-31. [PMID: 35287244 PMCID: PMC10078690 DOI: 10.1002/jat.4318] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 03/07/2022] [Accepted: 03/09/2022] [Indexed: 12/16/2022]
Abstract
Titanium dioxide (TiO2 ) is used extensively as a white pigment in the food industry, personal care, and a variety of products of everyday use. Although TiO2 has been categorized as a bioinert material, recent evidence has demonstrated different toxicity profiles of TiO2 nanoparticles (NPs) and a potential health risk to humans. Studies indicated that titanium dioxide enters the systemic circulation and accumulates in the lungs, liver, kidneys, spleen, heart, and central nervous system and may cause oxidative stress and tissue damage in these vital organs. Recently, some studies have raised concerns about the possible detrimental effects of TiO2 NPs on glucose homeostasis. However, the findings should be interpreted with caution due to the methodological issues. This article aims to evaluate current evidence regarding the effects of TiO2 NPs on glucose homeostasis, including possible underlying mechanisms. Furthermore, the limitations of current studies are discussed, which may provide a comprehensive understanding and new perspectives for future studies in this field.
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Affiliation(s)
| | - Beth L Mallard
- School of Health Sciences, Massey University, Wellington, New Zealand
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23
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Shi Q, Yang C, Zhang B, Chen D, Lu F, Zhao H. Bacillus coagulans Alleviates Intestinal Damage Induced by TiO2 Nanoparticles in Mice on a High-Fat Diet. Foods 2022; 11:foods11213368. [PMID: 36359981 PMCID: PMC9655532 DOI: 10.3390/foods11213368] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 10/13/2022] [Accepted: 10/24/2022] [Indexed: 11/29/2022] Open
Abstract
Titanium dioxide nanoparticles (TiO2 NPs) are generally added in considerable amounts to food as a food additive. Oral exposure to TiO2 NPs could induce intestinal damage, especially in obese individuals with a high-fat diet. The probiotic Bacillus coagulans (B. coagulans) exhibits good resistance in the gastrointestinal system and is beneficial to intestinal health. In this study, B. coagulans was used to treat intestinal damage caused by TiO2 NPs in high-fat-diet mice via two intervention methods: administration of TiO2 NPs and B. coagulans simultaneously and administration of TiO2 NPs followed by that of B. coagulans. The intervention with B. coagulans was found to reduce the inflammatory response and oxidative stress. A 16S rDNA sequencing analysis revealed that B. coagulans had increased the diversity of gut microbiota and optimized the composition of gut microbiota. Fecal metabolomics analysis indicated that B. coagulans had restored the homeostasis of sphingolipids and amino acid metabolism. The intervention strategy of administering TiO2 NPs followed by B. coagulans was found to be more effective. In conclusion, B. coagulans could alleviate intestinal damage induced by TiO2 NPs in high-fat-diet mice TiO2B. coagulans. Our results suggest a new avenue for interventions against intestinal damage induced by TiO2 NPs.
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Affiliation(s)
- Qingying Shi
- College of Biotechnology, Tianjin University of Science and Technology, 9 TEDA 13th Street, Tianjin 300457, China
| | - Chen Yang
- College of Biotechnology, Tianjin University of Science and Technology, 9 TEDA 13th Street, Tianjin 300457, China
| | - Bingjie Zhang
- College of Biotechnology, Tianjin University of Science and Technology, 9 TEDA 13th Street, Tianjin 300457, China
| | - Dongxiao Chen
- College of Biotechnology, Tianjin University of Science and Technology, 9 TEDA 13th Street, Tianjin 300457, China
| | - Fuping Lu
- College of Biotechnology, Tianjin University of Science and Technology, 9 TEDA 13th Street, Tianjin 300457, China
- Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin University of Science and Technology, Tianjin 300450, China
| | - Huabing Zhao
- College of Biotechnology, Tianjin University of Science and Technology, 9 TEDA 13th Street, Tianjin 300457, China
- Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin University of Science and Technology, Tianjin 300450, China
- Correspondence:
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24
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Cornu R, Béduneau A, Martin H. Ingestion of titanium dioxide nanoparticles: a definite health risk for consumers and their progeny. Arch Toxicol 2022; 96:2655-2686. [PMID: 35895099 DOI: 10.1007/s00204-022-03334-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Accepted: 07/05/2022] [Indexed: 01/13/2023]
Abstract
Titanium dioxide (TiO2) is one of the most commonly used nanomaterials in the world. Additive E171, which is used in the food industry, contains a nanometric particle fraction of TiO2. Oral exposure of humans to these nanoparticles (NPs) is intensive, leading to the question of their impact on health. Daily oral intake by rats of amounts of E171 that are relevant to human intake has been associated with an increased risk of chronic intestinal inflammation and carcinogenesis. Due to their food preferences, children are very exposed to this NP. Furthermore, maternal-foetal transfer of TiO2 NPs during pregnancy, as well as exposure of the offspring by breastfeeding, have been recently described. In France, the use of E171 in the production of foodstuffs was suspended in January 2020 as a precautionary measure. To provide some answers to this public health problem and help global regulatory agencies finalize their decisions, we reviewed in vitro and in vivo studies that address the effects of TiO2 NPs through oral exposure, especially their effects on the gastrointestinal tract, one of the most exposed tissues. Our review also highlights the effects of exposure on the offspring during pregnancy and by breastfeeding.
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Affiliation(s)
- Raphaël Cornu
- PEPITE EA4267, Univ. Bourgogne Franche-Comté, F-25000, Besançon, France
| | - Arnaud Béduneau
- PEPITE EA4267, Univ. Bourgogne Franche-Comté, F-25000, Besançon, France
| | - Hélène Martin
- PEPITE EA4267, Univ. Bourgogne Franche-Comté, F-25000, Besançon, France.
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25
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Metal nanoparticles: biomedical applications and their molecular mechanisms of toxicity. CHEMICAL PAPERS 2022. [DOI: 10.1007/s11696-022-02351-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
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26
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Baranowska-Wójcik E, Szwajgier D, Winiarska-Mieczan A. A review of research on the impact of E171/TiO 2 NPs on the digestive tract. J Trace Elem Med Biol 2022; 72:126988. [PMID: 35561571 DOI: 10.1016/j.jtemb.2022.126988] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2022] [Revised: 04/01/2022] [Accepted: 04/25/2022] [Indexed: 12/24/2022]
Abstract
Nanotechnology utilises particles of between 1 and 100 nm in size. In recent years, it has enjoyed widespread application in a variety of areas. However, this has also raised increasing concerns regarding the effects that the use of nanoparticles may have on human health. The nanoparticles of titanium dioxide (TiO2 NPs) are among the most promising nanomaterials and have already found wide use in cosmetics, medicine and, the food industry. A nano-sized (diameter < 100 nm) fraction of TiO2 is present, at a certain percentage, in the E171 ( in the EU) pigment commonly used as an additive in food, whose presence raises particular concerns in terms of its potential negative health impact. The consumption of E171 food additive is increasingly associated with disorders of the intestinal barrier, including intestinal dysbiosis. It may disrupt the normal functions of the gastrointestinal tract (GIT) including: enzymatic digestion of primary nutrients (lipids, proteins, or carbohydrates). The aim of this review is to provide a comprehensive and reliable overview of studies conducted in recent years in terms of the substance's potentially negative impact on human and animal alimentary systems.
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Affiliation(s)
- Ewa Baranowska-Wójcik
- Department of Biotechnology, Microbiology and Human Nutrition, University of Life Sciences in Lublin, Skromna 8, Lublin 20-704, Poland.
| | - Dominik Szwajgier
- Department of Biotechnology, Microbiology and Human Nutrition, University of Life Sciences in Lublin, Skromna 8, Lublin 20-704, Poland
| | - Anna Winiarska-Mieczan
- Institute of Animal Nutrition and Bromatology, Department of Bromatology and Food Physiology, University of Life Sciences in Lublin, Akademicka 13, Lublin 20-950, Poland
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27
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Acaricidal Efficacy of Biosynthesized Zinc Oxide Nanoparticles Against Hyalomma dromedarii (Acari: Ixodidae) and Their Toxic Effects on Swiss Albino Mice. Acta Parasitol 2022; 67:878-891. [PMID: 35316482 PMCID: PMC9165244 DOI: 10.1007/s11686-022-00530-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Accepted: 02/21/2022] [Indexed: 11/25/2022]
Abstract
Purpose The current study aimed to investigate the efficacy of zinc oxide nanoparticles (ZnO NPs) synthesized by Melia azedarach aqueous extract to control Hyalomma dromedarii tick, and to evaluate their toxic effects on Swiss albino mice. Methods ZnO NPs were synthesized using M. azedarach aqueous extract. UV–visible spectroscopy, Fourier transform infrared spectroscopy, scanning electron microscopy, and energy-dispersive spectroscopy were used to characterize the synthesized NPs. Egg, nymph, larva, and adult immersion tests were used for bioassay of tick stages with the synthesized ZnO NP. A toxicity study was performed on Swiss albino mice after treatment with 1/10 of the oral LD50 of ZnO NPs (8437 mg/kg) for 5 successive days by oral gavage. Results The LC50 of ZnO NPs on the eggs, larvae, and nymphs was 11.6, 8.03, and 3.9 mg/ml, respectively. The reproductive performance of females treated with ZnO NPs was lower than that of untreated females. The hematological results showed an insignificant increase in the level of white blood cells with normal red blood cells, hemoglobin, in addition to normal platelet count. The biochemical analysis showed an insignificant increased level (P > 0.05) of alkaline phosphatase and alanine aminotransferase. The liver and kidney suffered few histopathological changes after oral administration of ZnO NPs. Conclusion These results suggest that ZnO NPs have good acaricidal activity against eggs, larvae, and engorged nymphs of H. dromedarii. ZnO NPs minimized the number of eggs laid by engorged females and the hatchability of their eggs. ZnO NPs did not affect unfed adults. The toxicity results of the mice revealed insignificant changes in the hemogram, biochemistry, with liver and kidney suffering few histopathological changes. Future studies are needed to assess application routes (topical vs oral). Based on these findings, ZnO NPs may be incorporated in the control of camel tick H. dromedarii.
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Jalili P, Krause BC, Lanceleur R, Burel A, Jungnickel H, Lampen A, Laux P, Luch A, Fessard V, Hogeveen K. Chronic effects of two rutile TiO 2 nanomaterials in human intestinal and hepatic cell lines. Part Fibre Toxicol 2022; 19:37. [PMID: 35578293 PMCID: PMC9112549 DOI: 10.1186/s12989-022-00470-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Accepted: 04/05/2022] [Indexed: 01/05/2023] Open
Abstract
Background TiO2 nanomaterials (NMs) are present in a variety of food and personal hygiene products, and consumers are exposed daily to these NMs through oral exposition. While the bulk of ingested TiO2 NMs are eliminated rapidly in stool, a fraction is able to cross the intestinal epithelial barrier and enter systemic circulation from where NMs can be distributed to tissues, primarily liver and spleen. Daily exposure to TiO2 NMs, in combination with a slow rate of elimination from tissues, results in their accumulation within different tissues. Considerable evidence suggests that following oral exposure to TiO2 NMs, the presence of NMs in tissues is associated with a number of adverse effects, both in intestine and liver. Although numerous studies have been performed in vitro investigating the acute effects of TiO2 NMs in intestinal and hepatic cell models, considerably less is known about the effect of repeated exposure on these models. In this study, we investigated the cytotoxic effects of repeated exposure of relevant models of intestine and liver to two TiO2 NMs differing in hydrophobicity for 24 h, 1 week and 2 weeks at concentrations ranging from 0.3 to 80 µg/cm2. To study the persistence of these two NMs in cells, we included a 1-week recovery period following 24 h and 1-week treatments. Cellular uptake by TEM and ToF–SIMS analyses, as well as the viability and pro-inflammatory response were evaluated. Changes in the membrane composition in Caco-2 and HepaRG cells treated with TiO2 NMs for up to 2 weeks were also studied.
Results Despite the uptake of NM-103 and NM-104 in cells, no significant cytotoxic effects were observed in either Caco-2 or HepaRG cells treated for up to 2 weeks at NM concentrations up to 80 µg/cm2. In addition, no significant effects on IL-8 secretion were observed. However, significant changes in membrane composition were observed in both cell lines. Interestingly, while most of these phospholipid modifications were reversed following a 1-week recovery, others were not affected by the recovery period. Conclusion These findings indicate that although no clear effects on cytotoxicity were observed following repeated exposure of differentiated Caco-2 and HepaRG cells to TiO2 NMs, subtle effects on membrane composition could induce potential adverse effects in the long-term. Supplementary Information The online version contains supplementary material available at 10.1186/s12989-022-00470-1.
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Affiliation(s)
- Pégah Jalili
- Toxicology of Contaminants Unit, Fougères Laboratory, ANSES, French Agency for Food, Environmental and Occupational Health & Safety, 10 B rue Claude Bourgelat - Javené, 35306, Fougères, France
| | | | - Rachelle Lanceleur
- Toxicology of Contaminants Unit, Fougères Laboratory, ANSES, French Agency for Food, Environmental and Occupational Health & Safety, 10 B rue Claude Bourgelat - Javené, 35306, Fougères, France
| | - Agnès Burel
- MRic Cell Imaging Platform, BIOSIT, University of Rennes 1, 2 avenue du Pr Léon Bernard - CS 34317, 35043, Rennes, France
| | - Harald Jungnickel
- German Federal Institute for Risk Assessment, Max-Dohrn-Straße 8-10, 10589, Berlin, Germany
| | - Alfonso Lampen
- German Federal Institute for Risk Assessment, Max-Dohrn-Straße 8-10, 10589, Berlin, Germany
| | - Peter Laux
- German Federal Institute for Risk Assessment, Max-Dohrn-Straße 8-10, 10589, Berlin, Germany
| | - Andreas Luch
- German Federal Institute for Risk Assessment, Max-Dohrn-Straße 8-10, 10589, Berlin, Germany
| | - Valérie Fessard
- Toxicology of Contaminants Unit, Fougères Laboratory, ANSES, French Agency for Food, Environmental and Occupational Health & Safety, 10 B rue Claude Bourgelat - Javené, 35306, Fougères, France
| | - Kevin Hogeveen
- Toxicology of Contaminants Unit, Fougères Laboratory, ANSES, French Agency for Food, Environmental and Occupational Health & Safety, 10 B rue Claude Bourgelat - Javené, 35306, Fougères, France.
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29
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Xie D, Hu J, Wu T, Cao K, Luo X. Potential Biomarkers and Drugs for Nanoparticle-Induced Cytotoxicity in the Retina: Based on Regulation of Inflammatory and Apoptotic Genes. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19095664. [PMID: 35565057 PMCID: PMC9099825 DOI: 10.3390/ijerph19095664] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Revised: 05/03/2022] [Accepted: 05/05/2022] [Indexed: 02/01/2023]
Abstract
The eye is a superficial organ directly exposed to the surrounding environment. Thus, the toxicity of nanoparticle (NP) pollutants to the eye may be potentially severer relative to inner organs and needs to be monitored. However, the cytotoxic mechanisms of NPs on the eyes remain rarely reported. This study was to screen crucial genes associated with NPs-induced retinal injuries. The gene expression profiles in the retina induced by NPs [GSE49371: Au20, Au100, Si20, Si100; GSE49048: presumptive therapeutic concentration (PTC) TiO2, 10PTC TiO2] and commonly used retinal cell injury models (optic nerve injury procedure: GSE55228, GSE120257 and GSE131486; hypoxia exposure: GSE173233, GSE151610, GSE135844; H2O2 exposure: GSE122270) were obtained from the Gene Expression Omnibus database. A total of 381 differentially expressed genes (including 372 mRNAs and 9 lncRNAs) were shared between NP exposure and the optic nerve injury model when they were compared with their corresponding controls. Function enrichment analysis of these overlapped genes showed that Tlr2, Crhbp, Ccl2, Cxcl10, Fas, Irf8, Socs3, Stat3, Gbp6, Casp1 and Syk were involved in inflammatory- and apoptotic-related processes. Protein-protein interaction network analysis revealed eight of them (Tlr2, Ccl2, Cxcl10, Irf8, Socs3, Stat3, Casp1 and Syk) were hub genes. Moreover, Socs3 could interact with upstream Stat3 and downstream Fas/Casp1/Ccl2/Cxcl10; Irf8 could interact with upstream Tlr2, Syk and downstream Cxcl10. Competing endogenous RNAs network analysis identified Socs3, Irf8, Gdf6 and Crhbp could be regulated by lncRNAs and miRNAs (9330175E14Rik-mmu-miR-762-Socs3, 6430562O15Rik-mmu-miR-207-Irf8, Gm9866-mmu-miR-669b-5p-Gdf6, 4933406C10Rik-mmu-miR-9-5p-Crhbp). CMap-CTD database analyses indicated the expression levels of Tlr2, Ccl2, Cxcl10, Fas, Irf8, Socs3, Stat3, Gbp6, Casp1 and Syk could be reversed by folic acid. Crhbp and Gdf6 were also verified to be downregulated, while Tlr2, Ccl2, Irf8, Socs3 and Stat3 were upregulated in hypoxia/H2O2-induced retinal injury models. Hereby, our findings suggest that Crhbp, Irf8, Socs3 and Gdf6 as well as their upstream mRNAs, lncRNAs and miRNAs may be potential monitoring biomarkers and therapeutic targets for NP-induced retinal injuries. Folic acid supplementation may be a preventive and therapeutic approach.
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Affiliation(s)
- Dongli Xie
- College of Textile and Clothing Engineering, Soochow University, 199 Ren-Ai Road, Suzhou 215123, China; (D.X.); (J.H.)
| | - Jianchen Hu
- College of Textile and Clothing Engineering, Soochow University, 199 Ren-Ai Road, Suzhou 215123, China; (D.X.); (J.H.)
| | - Tong Wu
- Shanghai Jing Rui Yang Industrial Co., Ltd., 3188 Xiupu Road, Pudong New Area, Shanghai 200122, China;
| | - Kangli Cao
- Shanghai Institute of Spacecraft Equipment, 251 Huaning Road, Shanghai 200240, China;
| | - Xiaogang Luo
- College of Textile and Clothing Engineering, Soochow University, 199 Ren-Ai Road, Suzhou 215123, China; (D.X.); (J.H.)
- Correspondence: ; Tel.: +86-0512-67162531
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Tachibana K, Kawazoe S, Onoda A, Umezawa M, Takeda K. Effects of Prenatal Exposure to Titanium Dioxide Nanoparticles on DNA Methylation and Gene Expression Profile in the Mouse Brain. FRONTIERS IN TOXICOLOGY 2022; 3:705910. [PMID: 35295148 PMCID: PMC8915839 DOI: 10.3389/ftox.2021.705910] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 09/13/2021] [Indexed: 12/12/2022] Open
Abstract
Background and Objectives: Titanium dioxide nanoparticles (TiO2-NP) are important materials used in commercial practice. Reportedly, TiO2-NP exposure during pregnancy can affect the development of the central nervous system in mouse offspring; however, the underlying mechanism remains unknown. In the present study, we investigated the impact of prenatal TiO2-NP exposure on global DNA methylation and mRNA expression patterns in the brains of neonatal mice. Materials and Methods: Pregnant C57BL/6J mice were intratracheally administered a TiO2-NP suspension (100 μg/mouse) on gestational day 10.5, and brains were collected from male and female offspring at day 1 postpartum. After extraction of methylated DNA by immunoprecipitation, the DNA methylation profile was analyzed using a mouse CpG island microarray. Total RNA was obtained, and mRNA expression profiles were comprehensively assessed using microarray analysis. Results: Among genes in the CpG island microarray, DNA methylation was increased in 614 and 2,924 genes and decreased in 6,220 and 6,477 genes in male and female offspring, respectively. Combined with mRNA microarray analysis, 88 and 89 genes were upregulated (≥1.5-fold) accompanied by demethylation of CpG islands, whereas 13 and 33 genes were downregulated (≤0.67-fold) accompanied by methylation of CpG islands in male and female offspring mice, respectively. Gene Set Enrichment Analysis (GSEA) revealed that these genes were enriched in gene ontology terms related to the regulation of transcription factors, cell proliferation, and organism development. Additionally, MeSH terms related to stem cells and morphogenesis were enriched. Conclusion: Prenatal TiO2-NP exposure induced genome-wide alterations in DNA methylation and mRNA expression in the brains of male and female offspring. Based on GSEA findings, it can be speculated that prenatal TiO2-NP exposure causes adverse effects on brain functions by altering the DNA methylation state of the fetal brain, especially neural stem cells, resulting in the subsequent abnormal regulation of transcription factors that modulate development and differentiation.
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Affiliation(s)
- Ken Tachibana
- Division of Toxicology and Health Science, Faculty of Pharmaceutical Sciences, Sanyo-onoda City University, Sanyo-onoda, Japan.,The Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Organization for Research Advancement, Tokyo University of Science, Noda, Japan.,Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan
| | - Shotaro Kawazoe
- Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan
| | - Atsuto Onoda
- Division of Toxicology and Health Science, Faculty of Pharmaceutical Sciences, Sanyo-onoda City University, Sanyo-onoda, Japan.,The Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Organization for Research Advancement, Tokyo University of Science, Noda, Japan.,Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan
| | - Masakazu Umezawa
- The Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Organization for Research Advancement, Tokyo University of Science, Noda, Japan.,Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan.,Department of Materials Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science, Katsushika, Japan
| | - Ken Takeda
- Division of Toxicology and Health Science, Faculty of Pharmaceutical Sciences, Sanyo-onoda City University, Sanyo-onoda, Japan.,The Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Organization for Research Advancement, Tokyo University of Science, Noda, Japan.,Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan
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Wu B, Shao Y, Zhao W, Zheng Y, Wang Y, Sun D. Dual functions of epigallocatechin gallate surface-modified Au nanorods@selenium composites for near-infrared-II light-responsive synergistic antibacterial therapy. J Biomater Appl 2022; 36:1812-1825. [PMID: 35232312 DOI: 10.1177/08853282211048570] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Diseases caused by bacterial infections pose ever-increasing threats to human health, making it important to explore alternative antibacterial strategies. Herein, epigallocatechin gallate (EGCG) surface-modified Au nanorods@selenium composites (ASE NPs) were developed for synergistic NIR-II light-responsive antibacterial therapy. In vitro antibacterial experiments demonstrated the improved antibacterial effect of ASE NPs against Staphylococcus aureus (S. aureus) compared with EGCG alone. In addition, in vivo studies demonstrated that ASE NPs cured skin wound infections and sepsis in mice caused by S. aureus. Au nanorods with excellent photothermal conversion realized synergistic photothermal therapy (PTT) in the NIR-II biowindow with an improved penetration depth at a low power density. More importantly, toxicity analysis showed that the composites had no toxic effects on major organs. Thus, the EGCG surface-modified Au nanorods@selenium composites with an NIR-II light-responsive synergistic activity hold great promise for the effective treatment of drug-resistant bacterial infections.
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Affiliation(s)
- Bingbing Wu
- School of life sciences, 12486Anhui Agricultural University, Hefei, Anhui, P.R. China
| | - Yuyan Shao
- School of life sciences, 12486Anhui Agricultural University, Hefei, Anhui, P.R. China
| | - Wei Zhao
- School of life sciences, 12486Anhui Agricultural University, Hefei, Anhui, P.R. China
| | - Yunfang Zheng
- School of life sciences, 12486Anhui Agricultural University, Hefei, Anhui, P.R. China
| | - Yunsheng Wang
- School of life sciences, 12486Anhui Agricultural University, Hefei, Anhui, P.R. China
| | - Dongdong Sun
- School of life sciences, 12486Anhui Agricultural University, Hefei, Anhui, P.R. China
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Hofer S, Hofstätter N, Punz B, Hasenkopf I, Johnson L, Himly M. Immunotoxicity of nanomaterials in health and disease: Current challenges and emerging approaches for identifying immune modifiers in susceptible populations. WILEY INTERDISCIPLINARY REVIEWS. NANOMEDICINE AND NANOBIOTECHNOLOGY 2022; 14:e1804. [PMID: 36416020 PMCID: PMC9787548 DOI: 10.1002/wnan.1804] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Revised: 03/24/2022] [Accepted: 03/30/2022] [Indexed: 11/24/2022]
Abstract
Nanosafety assessment has experienced an intense era of research during the past decades driven by a vivid interest of regulators, industry, and society. Toxicological assays based on in vitro cellular models have undergone an evolution from experimentation using nanoparticulate systems on singular epithelial cell models to employing advanced complex models more realistically mimicking the respective body barriers for analyzing their capacity to alter the immune state of exposed individuals. During this phase, a number of lessons were learned. We have thus arrived at a state where the next chapters have to be opened, pursuing the following objectives: (1) to elucidate underlying mechanisms, (2) to address effects on vulnerable groups, (3) to test material mixtures, and (4) to use realistic doses on (5) sophisticated models. Moreover, data reproducibility has become a significant demand. In this context, we studied the emerging concept of adverse outcome pathways (AOPs) from the perspective of immune activation and modulation resulting in pro-inflammatory versus tolerogenic responses. When considering the interaction of nanomaterials with biological systems, protein corona formation represents the relevant molecular initiating event (e.g., by potential alterations of nanomaterial-adsorbed proteins). Using this as an example, we illustrate how integrated experimental-computational workflows combining in vitro assays with in silico models aid in data enrichment and upon comprehensive ontology-annotated (meta)data upload to online repositories assure FAIRness (Findability, Accessibility, Interoperability, Reusability). Such digital twinning may, in future, assist in early-stage decision-making during therapeutic development, and hence, promote safe-by-design innovation in nanomedicine. Moreover, it may, in combination with in silico-based exposure-relevant dose-finding, serve for risk monitoring in particularly loaded areas, for example, workplaces, taking into account pre-existing health conditions. This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials.
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Affiliation(s)
- Sabine Hofer
- Division of Allergy & Immunology, Department of Biosciences & Medical BiologyParis Lodron University of SalzburgSalzburgAustria
| | - Norbert Hofstätter
- Division of Allergy & Immunology, Department of Biosciences & Medical BiologyParis Lodron University of SalzburgSalzburgAustria
| | - Benjamin Punz
- Division of Allergy & Immunology, Department of Biosciences & Medical BiologyParis Lodron University of SalzburgSalzburgAustria
| | - Ingrid Hasenkopf
- Division of Allergy & Immunology, Department of Biosciences & Medical BiologyParis Lodron University of SalzburgSalzburgAustria
| | - Litty Johnson
- Division of Allergy & Immunology, Department of Biosciences & Medical BiologyParis Lodron University of SalzburgSalzburgAustria
| | - Martin Himly
- Division of Allergy & Immunology, Department of Biosciences & Medical BiologyParis Lodron University of SalzburgSalzburgAustria
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Mohapatra A, Sathiyamoorthy P, Park IK. Metallic Nanoparticle-Mediated Immune Cell Regulation and Advanced Cancer Immunotherapy. Pharmaceutics 2021; 13:1867. [PMID: 34834282 PMCID: PMC8622235 DOI: 10.3390/pharmaceutics13111867] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Revised: 10/30/2021] [Accepted: 11/01/2021] [Indexed: 12/13/2022] Open
Abstract
Cancer immunotherapy strategies leveraging the body's own immune system against cancer cells have gained significant attention due to their remarkable therapeutic efficacy. Several immune therapies have been approved for clinical use while expanding the modalities of cancer therapy. However, they are still not effective in a broad range of cancer patients because of the typical immunosuppressive microenvironment and limited antitumor immunity achieved with the current treatment. Novel approaches, such as nanoparticle-mediated cancer immunotherapies, are being developed to overcome these challenges. Various types of nanoparticles, including liposomal, polymeric, and metallic nanoparticles, are reported for the development of effective cancer therapeutics. Metallic nanoparticles (MNPs) are one of the promising candidates for anticancer therapy due to their unique theranostic properties and are thus explored as both imaging and therapeutic agents. In addition, MNPs offer a dense surface functionalization to target tumor tissue and deliver genetic, therapeutic, and immunomodulatory agents. Furthermore, MNPs interact with the tumor microenvironment (TME) and regulate the levels of tumor hypoxia, glutathione (GSH), and reactive oxygen species (ROS) for remodulation of TME for successful therapy. In this review, we discuss the role of nanoparticles in tumor microenvironment modulation and anticancer therapy. In particular, we evaluated the response of MNP-mediated immune cells, such as dendritic cells, macrophages, T cells and NK cells, against tumor cells and analyzed the role of MNP-based cancer therapies in regulating the immunosuppressive environment.
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Affiliation(s)
- Adityanarayan Mohapatra
- Department of Biomedical Sciences, Chonnam National University Medical School, Hwasun 58128, Korea; (A.M.); (P.S.)
- Biomedical Science Graduate Program (BMSGP), Chonnam National University, Hwasun 58128, Korea
| | - Padmanaban Sathiyamoorthy
- Department of Biomedical Sciences, Chonnam National University Medical School, Hwasun 58128, Korea; (A.M.); (P.S.)
- Biomedical Science Graduate Program (BMSGP), Chonnam National University, Hwasun 58128, Korea
| | - In-Kyu Park
- Department of Biomedical Sciences, Chonnam National University Medical School, Hwasun 58128, Korea; (A.M.); (P.S.)
- Biomedical Science Graduate Program (BMSGP), Chonnam National University, Hwasun 58128, Korea
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Li B, Tang M. Research progress of nanoparticle toxicity signaling pathway. Life Sci 2020; 263:118542. [DOI: 10.1016/j.lfs.2020.118542] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Revised: 09/26/2020] [Accepted: 09/28/2020] [Indexed: 01/19/2023]
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Vilas-Boas V, Vinken M. Hepatotoxicity induced by nanomaterials: mechanisms and in vitro models. Arch Toxicol 2020; 95:27-52. [PMID: 33155068 DOI: 10.1007/s00204-020-02940-x] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Accepted: 10/20/2020] [Indexed: 12/14/2022]
Abstract
The unique physicochemical properties of materials at nanoscale have opened a plethora of opportunities for applications in the pharmaceutical and medical field, but also in consumer products from food and cosmetics industries. As a consequence, daily human exposure to nanomaterials through distinct routes is considerable and, therefore, may raise health concerns. Many nanomaterials have been described to accumulate and induce adversity in the liver. Among these, silica and some types of metallic nanoparticles are the most broadly used in consumer products and, therefore, the most studied and reported. The reviewed literature was collected from PubMed.gov during the month of March 2020 using the search words "nanomaterials induced hepatotoxicity", which yielded 181 papers. This present paper reviews the hepatotoxic effects of nanomaterials described in in vitro and in vivo studies, with emphasis on the underlying mechanisms. The induction of oxidative stress and inflammation are the manifestations of toxicity most frequently reported following exposure of cells or animal models to different nanomaterials. Furthermore, the available in vitro models for the evaluation of the hepatotoxic effects of nanomaterials are discussed, highlighting the continuous interest in the development of more advanced and reliable in vitro models for nanotoxicology.
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Affiliation(s)
- Vânia Vilas-Boas
- Department of In Vitro Toxicology, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium
| | - Mathieu Vinken
- Department of In Vitro Toxicology, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium.
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Akyol S, Akgun MY, Yetmez M, Hanci M, Oktar FN, Ben-Nissan B. Comparative Analysis of NF-κB in the MyD88-Mediated Pathway After Implantation of Titanium Alloy and Stainless Steel and the Role of Regulatory T Cells. World Neurosurg 2020; 144:e138-e148. [PMID: 32781150 DOI: 10.1016/j.wneu.2020.08.016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Accepted: 08/03/2020] [Indexed: 11/18/2022]
Abstract
OBJECTIVE Development of immunologically smart implants, integrated to biological systems, is a key aim to minimize the inflammatory response of the host to biomaterial implants. METHODS The aim of this study is to investigate the influence of titanium alloy and stainless steel implants on immunological responses in rats by comparative analysis of nuclear factor kappa B (NF-κB) profiles in the activation of inflammatory signaling pathways and the role of CD4+CD25+Foxp3+. RESULTS Both Ti alloy and stainless steel alloy group implantation affect Toll-like receptors-4 pathways and CD4+CD25+ regulatory T cells in different ways. CONCLUSIONS Results show that NF-κB/p65 and NF-κB1/p50 possess potential as a therapeutic target in the prevention of adverse reactions to metal, especially for controlling inflammation after the implantation.
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Affiliation(s)
- Sibel Akyol
- Department of Physiology, Istanbul University-Cerrahpasa, Istanbul, Turkey; Faculty of Science, School of Life Sciences, University of Technology Sydney, Sydney, Australia
| | - Mehmet Yigit Akgun
- Department of Neurosurgery, High Specialized Hospital, Kirikkale, Turkey.
| | - Mehmet Yetmez
- Department of Mechanical Engineering, Faculty of Engineering, Zonguldak Bulent Ecevit University, Zonguldak, Turkey
| | - Murat Hanci
- Department of Neurosurgery, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Faik Nuzhet Oktar
- Faculty of Technology, Advanced Nanomaterials Research Laboratory, Marmara University, Istanbul, Turkey
| | - Besim Ben-Nissan
- Faculty of Science, School of Life Sciences, University of Technology Sydney, Sydney, Australia
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Mohammed ET, Safwat GM. Grape Seed Proanthocyanidin Extract Mitigates Titanium Dioxide Nanoparticle (TiO 2-NPs)-Induced Hepatotoxicity Through TLR-4/NF-κB Signaling Pathway. Biol Trace Elem Res 2020; 196:579-589. [PMID: 31701464 DOI: 10.1007/s12011-019-01955-5] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2019] [Accepted: 10/24/2019] [Indexed: 01/01/2023]
Abstract
With the progress of nanotechnology, the adverse effects of nanoscale materials are receiving much attention. Inhibition of toll-like receptor 4 (TLR-4)/nuclear factor kappa B (NF-κB) signaling is a hallmark for downregulating the expression of many inflammatory genes implicated in oxidative stress. Therefore, the present study aimed to demonstrate the influence of grape seed proanthocyanidin extract (GSE) on the hepatic TLR-4/ NF-κB signaling pathway in TiO2-NP-induced liver damage in rats. Forty male Albino rats were divided into 4 groups (n = 10): G1 was used as a control, G2 received TiO2-NPs (500 mg/kg/day orally) from the 17th to 30th day (acute toxicity), G3 received GSE (75 mg/kg/day orally) for 30 days, and G4 pre- and co-treated with GSE (for 30 days) and TiO2-NPs (from the 17th to 30th day), with the aforementioned doses. TiO2-NPs induced severe hepatic injury that was indicated by biochemical alterations in serum liver markers (acetylcholinesterase, ALT, ALP, total proteins, albumin, and direct bilirubin), oxidative stress indicators (MDA, GSH, and catalase), and histopathological alterations as well. Moreover, TiO2-NPs triggered an inflammatory response via the upregulation of TLR-4, NF-κB, NIK, and TNF-α mRNA expressions. Pre- and co-treatments with GSE alleviated the detrimental effects of TiO2-NPs which were enforced by the histopathological improvements. These results indicated that GSE effectively protected against TiO2-NP-induced hepatotoxicity via the inhibition of TLR-4/NF-κB signaling and hence suppressed the production of pro inflammatory cytokines such as TNF-α and improved the antioxidant status of the rats.
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Affiliation(s)
- Eman T Mohammed
- Department of Biochemistry, Faculty of Veterinary Medicine, Beni-Suef University, Beni Suef, Egypt.
| | - Ghada M Safwat
- Department of Biochemistry, Faculty of Veterinary Medicine, Beni-Suef University, Beni Suef, Egypt
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Malaviya P, Shukal D, Vasavada AR. Nanotechnology-based Drug Delivery, Metabolism and Toxicity. Curr Drug Metab 2020; 20:1167-1190. [PMID: 31902350 DOI: 10.2174/1389200221666200103091753] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Revised: 10/02/2019] [Accepted: 11/23/2019] [Indexed: 11/22/2022]
Abstract
BACKGROUND Nanoparticles (NPs) are being used extensively owing to their increased surface area, targeted delivery and enhanced retention. NPs have the potential to be used in many disease conditions. Despite widespread use, their toxicity and clinical safety still remain a major concern. OBJECTIVE The purpose of this study was to explore the metabolism and toxicological effects of nanotherapeutics. METHODS Comprehensive, time-bound literature search was done covering the period from 2010 till date. The primary focus was on the metabolism of NP including their adsorption, degradation, clearance, and bio-persistence. This review also focuses on updated investigations on NPs with respect to their toxic effects on various in vitro and in vivo experimental models. RESULTS Nanotechnology is a thriving field of biomedical research and an efficient drug delivery system. Further their applications are under investigation for diagnosis of disease and as medical devices. CONCLUSION The toxicity of NPs is a major concern in the application of NPs as therapeutics. Studies addressing metabolism, side-effects and safety of NPs are desirable to gain maximum benefits of nanotherapeutics.
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Affiliation(s)
- Pooja Malaviya
- Department of Cell and Molecular Biology, Iladevi Cataract and IOL Research Centre, Memnagar, Ahmedabad 380052, India.,Ph.D. Scholars, Manipal Academy of Higher Education, Manipal, India
| | - Dhaval Shukal
- Department of Cell and Molecular Biology, Iladevi Cataract and IOL Research Centre, Memnagar, Ahmedabad 380052, India.,Ph.D. Scholars, Manipal Academy of Higher Education, Manipal, India
| | - Abhay R Vasavada
- Department of Cell and Molecular Biology, Iladevi Cataract and IOL Research Centre, Memnagar, Ahmedabad 380052, India
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Brand W, Peters RJB, Braakhuis HM, Maślankiewicz L, Oomen AG. Possible effects of titanium dioxide particles on human liver, intestinal tissue, spleen and kidney after oral exposure. Nanotoxicology 2020; 14:985-1007. [PMID: 32619159 DOI: 10.1080/17435390.2020.1778809] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Recent studies reported adverse liver effects and intestinal tumor formation after oral exposure to titanium dioxide (TiO2). Other oral toxicological studies, however, observed no effects on liver and intestine, despite prolonged exposure and/or high doses. In the present assessment, we aimed to better understand whether TiO2 can induce such effects at conditions relevant for humans. Therefore, we focused not only on the clinical and histopathological observations, but also used Adverse Outcome Pathways (AOPs) to consider earlier steps (Key Events). In addition, aiming for a more accurate risk assessment, the available information on organ concentrations of Ti (resulting from exposure to TiO2) from oral animal studies was compared to recently reported concentrations found in human postmortem organs. The overview obtained with the AOP approach indicates that TiO2 can trigger a number of key events in liver and intestine: Reactive Oxygen Species (ROS) generation, induction of oxidative stress and inflammation. TiO2 seems to be able to exert these early effects in animal studies at Ti liver concentrations that are only a factor of 30 and 6 times higher than the median and highest liver concentration found in humans, respectively. This confirms earlier conclusions that adverse effects on the liver in humans as a result of (oral) TiO2 exposure cannot be excluded. Data for comparison with Ti levels in human intestinal tissue, spleen and kidney with effect concentrations were too limited to draw firm conclusions. The Ti levels, though, are similar or higher than those found in liver, suggesting these tissues may be relevant too.
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Affiliation(s)
- Walter Brand
- Centre for Safety of Substances and Products, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands
| | - Ruud J B Peters
- Wageningen Food Safety Research (WFSR), Wageningen, the Netherlands
| | - Hedwig M Braakhuis
- Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands
| | - Lidka Maślankiewicz
- Centre for Safety of Substances and Products, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands
| | - Agnes G Oomen
- Centre for Safety of Substances and Products, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands
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40
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MicroRNA Response and Toxicity of Potential Pathways in Human Colon Cancer Cells Exposed to Titanium Dioxide Nanoparticles. Cancers (Basel) 2020; 12:cancers12051236. [PMID: 32423014 PMCID: PMC7281448 DOI: 10.3390/cancers12051236] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2020] [Revised: 04/22/2020] [Accepted: 04/26/2020] [Indexed: 12/13/2022] Open
Abstract
Titanium dioxide nanoparticles (TiO2-NPs) are widely used for biomedical and food applications, the toxicity of TiO2-NPs in vivo and in vitro has been elucidated, but the underlying cytotoxicity of TiO2-NPs against microRNA remains largely unknown. The purpose of this study was to analyze microRNA profiling induced by TiO2-NPs against NCM460 and HCT116 cell lines. Comparative analysis identified 34 and 24 microRNAs were significantly altered in the TiO2-NPs treated cells at concentrations of 3 μg/mL and 30 μg/mL, respectively. Functional classification demonstrated that a large proportion of genes involved in metabolism, human disease, and environmental information process were significantly upregulated by TiO2-NPs. Bioinformatics analysis suggested that microRNA 378 might be an early indicator of cellular response to exogenous stimuli with apoptotic signals. Furthermore, TiO2-NPs significantly altered the expression of microRNA 378b and 378g in HCT116 and NCM460 cell lines at different concentrations from 3 to 6 μg/mL. These concentrations elicit high-sensitivity of stimuli response in colon cancer cells when exposed to the slight doses of TiO2-NPs. Our study indicated that microRNAs 378b and 378g may play an important role in TiO2-NPs-mediated colonic cytotoxicity, which may provide a valuable insight into the molecular mechanisms of potential risks in colitis and colon cancer.
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Bobori D, Dimitriadi A, Karasiali S, Tsoumaki-Tsouroufli P, Mastora M, Kastrinaki G, Feidantsis K, Printzi A, Koumoundouros G, Kaloyianni M. Common mechanisms activated in the tissues of aquatic and terrestrial animal models after TiO 2 nanoparticles exposure. ENVIRONMENT INTERNATIONAL 2020; 138:105611. [PMID: 32126387 DOI: 10.1016/j.envint.2020.105611] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Revised: 02/03/2020] [Accepted: 02/24/2020] [Indexed: 06/10/2023]
Abstract
Titanium dioxide nanoparticles (TiO2-NPs) are among the most popular manufactured and widely used nanoparticles. They are released into the environment, affecting terrestrial and aquatic ecosystems, with unexpected consequences to organisms and human health. The present study investigates the mediated toxicity imposed to the freshwater fish species, zebrafish (Danio rerio) and the prussian carp (Carassius gibelio), and to the terrestrial land snail Cornu aspersum, after their exposure to sublethal concentrations of TiO2-NPs. Oxidative, proteolytic, genotoxic and apoptotic parameters in fish liver and gills, as well as on snail hemocytes were studied and the swimming performance was estimated in order to (a) estimate and suggest the most susceptible animal, and (b) propose a common battery of biomarkers as the most suitable indicator for biomonitoring studies against TiO2-NPs. Our in vivo experiments demonstrated that NPs induced detrimental effects on animal physiology and swimming behavior, while no general pattern was observed in species and tissues responsiveness. Generally, TiO2-NPs seemed to activate a group of molecules that are common for aquatic as well as terrestrial animals, implying the existence of a conserved mechanism. It seems that after exposure to TiO2-NPs, a common mechanism is activated that involves the stimulation of immune system with the production of ROS, damage of lysosomal membrane, protein carbonylation, lipid peroxidation, DNA damage, following proteolysis by ubiquitin and finally apoptosis. Thus, the simultaneous use of the latter biomarkers could be suggested as a reliable multi parameter approach for biomonitoring of aquatic and terrestrial ecosystems against TiO2-NPs.
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Affiliation(s)
- Dimitra Bobori
- Laboratory of Ichthyology, Department of Zoology, School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | | | - Stavri Karasiali
- Laboratory of Ichthyology, Department of Zoology, School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece; Laboratory of Animal Physiology, Department of Zoology, School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Paraskevi Tsoumaki-Tsouroufli
- Laboratory of Ichthyology, Department of Zoology, School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece; Laboratory of Animal Physiology, Department of Zoology, School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Marina Mastora
- Laboratory of Animal Physiology, Department of Zoology, School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Georgia Kastrinaki
- Aerosol & Particle Technology Laboratory, CERTH/CPERI, Thessaloniki, Greece
| | - Konstantinos Feidantsis
- Laboratory of Animal Physiology, Department of Zoology, School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Alice Printzi
- Biology Department, University of Crete, Herakleion, Crete, Greece
| | | | - Martha Kaloyianni
- Laboratory of Animal Physiology, Department of Zoology, School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
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Wang Z, Zhai X, Sun Y, Yin C, Yang E, Wang W, Sun D. Antibacterial activity of chlorogenic acid-loaded SiO 2 nanoparticles caused by accumulation of reactive oxygen species. NANOTECHNOLOGY 2020; 31:185101. [PMID: 31995525 DOI: 10.1088/1361-6528/ab70fb] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Diseases caused by pathogenic bacilli pose an increasing threat to human health. A common feature of these bacteria is a complete cell wall; therefore, drugs that can penetrate this protective barrier could be used as a novel approach for treating these infections. Here we present a simple method for synthesizing a silica mesoporous material loaded with cadmium selenide (CdSe) and chlorogenic acid. Using UV-visible, fluorescence, and infrared imaging in combination with transmission electron microscopy, it was shown that CdSe and chlorogenic acid could be successfully embedded in the mesopores of silica nanoparticles (CSC NPs), and these NPs presented with a strong fluorescence, uniform size, and good dispersion. Additionally, the results of these analyses indicated that the fluorescence of the CSC NPs was localized within the cells of Escherichia coli and Bacillus subtilis, signifying that these NPs could breach the cell wall and enter the cells of these two bacilli. Additional assessments found that these CSC NPs inhibited the proliferation of the bacteria by disrupting the cell wall, and this was most likely due to the overproduction of reactive oxygen species induced by chlorogenic acid. Importantly, histopathology analysis indicated that the CSC NPs had limited side effects and high biocompatibility.
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Affiliation(s)
- Zekun Wang
- School of life sciences, Anhui Agricultural University, Hefei 230036, People's Republic of China
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Brandão F, Fernández-Bertólez N, Rosário F, Bessa MJ, Fraga S, Pásaro E, Teixeira JP, Laffon B, Valdiglesias V, Costa C. Genotoxicity of TiO 2 Nanoparticles in Four Different Human Cell Lines (A549, HEPG2, A172 and SH-SY5Y). NANOMATERIALS (BASEL, SWITZERLAND) 2020; 10:E412. [PMID: 32120981 PMCID: PMC7152841 DOI: 10.3390/nano10030412] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 02/24/2020] [Accepted: 02/25/2020] [Indexed: 11/16/2022]
Abstract
Titanium dioxide nanoparticles (TiO2 NPs) have a wide variety of applications in many consumer products, including as food additives, increasing the concern about the possible hazards that TiO2 NPs may pose to human health. Although most previous studies have focused on the respiratory system, ingestion must also be considered as an important exposure route. Furthermore, after inhalation or ingestion, TiO2 NPs can reach several organs, such as the liver, brain or lungs. Taking this into consideration, the present study focuses on the uptake and potential genotoxicity (micronuclei induction) of TiO2 NPs on four human cell lines of diverse origin: lung cells (A549), liver cells (HepG2), glial cells (A172) and neurons (SH-SY5Y), using flow cytometry methods. Results showed a concentration-, time- and cell-type- dependent increase in TiO2 NPs uptake but no significant induction of micronuclei in any of the tested conditions. Data obtained reinforce the importance of cell model and testing protocols choice for toxicity assessment. However, some questions remain to be answered, namely on the role of cell culture media components on the agglomeration state and mitigation of TiO2 NPs toxic effects.
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Affiliation(s)
- Fátima Brandão
- EPIUnit—Instituto de Saúde Pública, Universidade do Porto, Rua das Taipas, 4050-600 Porto, Portugal; (F.B.); (F.R.); (M.J.B.); (S.F.); (C.C.)
- Environmental Health Department, National Institute of Health, Rua Alexandre Herculano 321, 4000-053 Porto, Portugal
- ICBAS—Institute of Biomedical Sciences Abel Salazar, U. Porto—University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
| | - Natalia Fernández-Bertólez
- Universidade da Coruña, DICOMOSA Group, Department of Psychology, Area of Psychobiology, Edificio de Servicios Centrales de Investigación, Campus Elviña s/n, 15071 A Coruña, Spain; (N.F.-B.); (E.P.); (B.L.); (V.V.)
| | - Fernanda Rosário
- EPIUnit—Instituto de Saúde Pública, Universidade do Porto, Rua das Taipas, 4050-600 Porto, Portugal; (F.B.); (F.R.); (M.J.B.); (S.F.); (C.C.)
- Environmental Health Department, National Institute of Health, Rua Alexandre Herculano 321, 4000-053 Porto, Portugal
| | - Maria João Bessa
- EPIUnit—Instituto de Saúde Pública, Universidade do Porto, Rua das Taipas, 4050-600 Porto, Portugal; (F.B.); (F.R.); (M.J.B.); (S.F.); (C.C.)
- Environmental Health Department, National Institute of Health, Rua Alexandre Herculano 321, 4000-053 Porto, Portugal
- ICBAS—Institute of Biomedical Sciences Abel Salazar, U. Porto—University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
| | - Sónia Fraga
- EPIUnit—Instituto de Saúde Pública, Universidade do Porto, Rua das Taipas, 4050-600 Porto, Portugal; (F.B.); (F.R.); (M.J.B.); (S.F.); (C.C.)
- Environmental Health Department, National Institute of Health, Rua Alexandre Herculano 321, 4000-053 Porto, Portugal
| | - Eduardo Pásaro
- Universidade da Coruña, DICOMOSA Group, Department of Psychology, Area of Psychobiology, Edificio de Servicios Centrales de Investigación, Campus Elviña s/n, 15071 A Coruña, Spain; (N.F.-B.); (E.P.); (B.L.); (V.V.)
| | - João Paulo Teixeira
- EPIUnit—Instituto de Saúde Pública, Universidade do Porto, Rua das Taipas, 4050-600 Porto, Portugal; (F.B.); (F.R.); (M.J.B.); (S.F.); (C.C.)
- Environmental Health Department, National Institute of Health, Rua Alexandre Herculano 321, 4000-053 Porto, Portugal
| | - Blanca Laffon
- Universidade da Coruña, DICOMOSA Group, Department of Psychology, Area of Psychobiology, Edificio de Servicios Centrales de Investigación, Campus Elviña s/n, 15071 A Coruña, Spain; (N.F.-B.); (E.P.); (B.L.); (V.V.)
| | - Vanessa Valdiglesias
- Universidade da Coruña, DICOMOSA Group, Department of Psychology, Area of Psychobiology, Edificio de Servicios Centrales de Investigación, Campus Elviña s/n, 15071 A Coruña, Spain; (N.F.-B.); (E.P.); (B.L.); (V.V.)
- Universidade da Coruña, Centro de Investigacións Científicas Avanzadas (CICA), Campus Elviña, 15071 A Coruña, Spain
| | - Carla Costa
- EPIUnit—Instituto de Saúde Pública, Universidade do Porto, Rua das Taipas, 4050-600 Porto, Portugal; (F.B.); (F.R.); (M.J.B.); (S.F.); (C.C.)
- Environmental Health Department, National Institute of Health, Rua Alexandre Herculano 321, 4000-053 Porto, Portugal
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Vasilichin VA, Tsymbal SA, Fakhardo AF, Anastasova EI, Marchenko AS, Shtil AA, Vinogradov VV, Koshel EI. Effects of Metal Oxide Nanoparticles on Toll-Like Receptor mRNAs in Human Monocytes. NANOMATERIALS (BASEL, SWITZERLAND) 2020; 10:E127. [PMID: 32284505 PMCID: PMC7023015 DOI: 10.3390/nano10010127] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Revised: 12/30/2019] [Accepted: 01/05/2020] [Indexed: 01/04/2023]
Abstract
For the widespread application of nanotechnology in biomedicine, it is necessary to obtain information about their safety. A critical problem is presented by the host immune responses to nanomaterials. It is assumed that the innate immune system plays a crucial role in the interaction of nanomaterials with the host organism. However, there are only fragmented data on the activation of innate immune system factors, such as toll-like receptors (TLRs), by some nanoparticles (NPs). In this study, we investigated TLRs' activation by clinically relevant and promising NPs, such as Fe3O4, TiO2, ZnO, CuO, Ag2O, and AlOOH. Cytotoxicity and effects on innate immunity factors were studied in THP-1(Tohoku Hospital Pediatrics-1) cell culture. NPs caused an increase of TLR-4 and -6 expression, which was comparable with the LPS-induced level. This suggests that the studied NPs can stimulate the innate immune system response inside the host. The data obtained should be taken into account in future research and to create safe-by-design biomedical nanomaterials.
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Affiliation(s)
- Vladislav A. Vasilichin
- International Institute Solution Chemistry of Advanced Materials and Technologies, ITMO University, 197101 St. Petersburg, Russia; (V.A.V.); (S.A.T.); (A.F.F.); (E.I.A.); (A.S.M.); (A.A.S.)
| | - Sergey A. Tsymbal
- International Institute Solution Chemistry of Advanced Materials and Technologies, ITMO University, 197101 St. Petersburg, Russia; (V.A.V.); (S.A.T.); (A.F.F.); (E.I.A.); (A.S.M.); (A.A.S.)
| | - Anna F. Fakhardo
- International Institute Solution Chemistry of Advanced Materials and Technologies, ITMO University, 197101 St. Petersburg, Russia; (V.A.V.); (S.A.T.); (A.F.F.); (E.I.A.); (A.S.M.); (A.A.S.)
| | - Elizaveta I. Anastasova
- International Institute Solution Chemistry of Advanced Materials and Technologies, ITMO University, 197101 St. Petersburg, Russia; (V.A.V.); (S.A.T.); (A.F.F.); (E.I.A.); (A.S.M.); (A.A.S.)
| | - Andrey S. Marchenko
- International Institute Solution Chemistry of Advanced Materials and Technologies, ITMO University, 197101 St. Petersburg, Russia; (V.A.V.); (S.A.T.); (A.F.F.); (E.I.A.); (A.S.M.); (A.A.S.)
| | - Alexander A. Shtil
- International Institute Solution Chemistry of Advanced Materials and Technologies, ITMO University, 197101 St. Petersburg, Russia; (V.A.V.); (S.A.T.); (A.F.F.); (E.I.A.); (A.S.M.); (A.A.S.)
- Blokhin National Medical Research Center of Oncology, 115478 Moscow, Russia
| | - Vladimir V. Vinogradov
- International Institute Solution Chemistry of Advanced Materials and Technologies, ITMO University, 197101 St. Petersburg, Russia; (V.A.V.); (S.A.T.); (A.F.F.); (E.I.A.); (A.S.M.); (A.A.S.)
| | - Elena I. Koshel
- International Institute Solution Chemistry of Advanced Materials and Technologies, ITMO University, 197101 St. Petersburg, Russia; (V.A.V.); (S.A.T.); (A.F.F.); (E.I.A.); (A.S.M.); (A.A.S.)
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Cornu R, Béduneau A, Martin H. Influence of nanoparticles on liver tissue and hepatic functions: A review. Toxicology 2019; 430:152344. [PMID: 31843632 DOI: 10.1016/j.tox.2019.152344] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Revised: 11/14/2019] [Accepted: 12/12/2019] [Indexed: 12/16/2022]
Abstract
Due to the increasing interest in nanotechnology in very large application fields, including biotechnology, electronics and food industries, humans are increasingly exposed to nanoparticles (NPs). Consequently, the question about the safety of these nanomaterials and their impact on human health is a legitimate concern. The liver is the primary organ of detoxification and is one of the tissues that is most exposed to NPs. When they reach the bloodstream, NPs are mainly internalized by liver cells. This review focuses on recent in vitro and in vivo studies addressing the effects of organic and inorganic NPs on the liver. Specifically, the impact of the NPs on hepatic enzyme activities, the inflammatory response and genotoxicity processes will be described. Depending on the physicochemical parameters of the NPs and the conditions of exposure, NPs could lead to global liver injury.
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Affiliation(s)
- Raphaël Cornu
- PEPITE EA4267, Univ. Bourgogne Franche-Comté, F-25000 Besançon, France.
| | - Arnaud Béduneau
- PEPITE EA4267, Univ. Bourgogne Franche-Comté, F-25000 Besançon, France.
| | - Hélène Martin
- PEPITE EA4267, Univ. Bourgogne Franche-Comté, F-25000 Besançon, France.
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Ghosh S, Ghosh I, Chakrabarti M, Mukherjee A. Genotoxicity and biocompatibility of superparamagnetic iron oxide nanoparticles: Influence of surface modification on biodistribution, retention, DNA damage and oxidative stress. Food Chem Toxicol 2019; 136:110989. [PMID: 31760074 DOI: 10.1016/j.fct.2019.110989] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Revised: 11/09/2019] [Accepted: 11/19/2019] [Indexed: 12/20/2022]
Abstract
Superparamagnetic iron oxide nanoparticles (SPION) require stable surface modifications to render safe nanocapsules for biomedical applications. Herein, two types of surface modified poly(lactic-co-glycolic acid)-encapsulated SPION were synthesized using either α-tocopheryl-polyetheleneglycol-succinate (TPGS) or didodecyl-dimethyl-ammonium-bromide (DMAB) as surfactants by emulsification. SPION-TPGS (180 nm) was larger than SPION-DMAB (25 nm) and uncoated SPION (10 nm). Both formulations were positively charged and induced lower cyto-genotoxicity and ROS generation than uncoated SPION in human lymphocytes. SPION-DMAB was least cyto-genotoxic among the three. Based on these results, mice were gavaged with the formulations for 5 consecutive days and biocompatibility studies were performed on the 7th and 21st days. ICP-AES and Prussian blue staining revealed the internalization of SPION-DMAB in brain and spleen, and SPION-TPGS in liver and kidney on day 7. This was correlated with high DNA damage and oxidative stress in the same organs. Substantial clearance of Fe was accompanied by reduced genotoxicity and oxidative stress on day 21. Therefore, SPION-DMAB can be further studied for oral drug delivery to the brain and imaging of cerebral tissue without any functional ligand or external magnetic field.
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Affiliation(s)
- Swarupa Ghosh
- Cell Biology and Genetic Toxicology Laboratory, Centre of Advanced Study, Department of Botany, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, 700 019, India; School of Life Science and Biotechnology, Adamas University, West Bengal, India
| | - Ilika Ghosh
- Cell Biology and Genetic Toxicology Laboratory, Centre of Advanced Study, Department of Botany, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, 700 019, India; Graduate School of Science and Engineering, Saitama University, 255, Shimo-okubo, Sakura-ku, Saitama-shi, Saitama, 338-8570, Japan
| | - Manoswini Chakrabarti
- Cell Biology and Genetic Toxicology Laboratory, Centre of Advanced Study, Department of Botany, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, 700 019, India
| | - Anita Mukherjee
- Cell Biology and Genetic Toxicology Laboratory, Centre of Advanced Study, Department of Botany, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, 700 019, India.
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Abo‐zeid Y, Williams GR. The potential anti‐infective applications of metal oxide nanoparticles: A systematic review. WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY 2019; 12:e1592. [DOI: 10.1002/wnan.1592] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/21/2019] [Revised: 09/01/2019] [Accepted: 09/04/2019] [Indexed: 12/13/2022]
Affiliation(s)
- Yasmin Abo‐zeid
- School of Pharmacy Helwan University Cairo Egypt
- UCL School of Pharmacy University College London London UK
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Nazer S, Andleeb S, Ali S, Gulzar N, Iqbal T, Khan MAR, Raza A. Synergistic Antibacterial Efficacy of Biogenic Synthesized Silver Nanoparticles using Ajuga bractosa with Standard Antibiotics: A Study Against Bacterial Pathogens. Curr Pharm Biotechnol 2019; 21:206-218. [PMID: 31573882 DOI: 10.2174/1389201020666191001123219] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Revised: 06/29/2019] [Accepted: 08/29/2019] [Indexed: 01/09/2023]
Abstract
BACKGROUND Multi-drug resistance in bacterial pathogens is a major concern of today. Green synthesis technology is being used to cure infectious diseases. OBJECTIVES The aim of the current research was to analyze the antibacterial, antioxidant, and phytochemical screening of green synthesized silver nanoparticles using Ajuga bracteosa. METHODS Extract of A. bracteosa was prepared by maceration technique. Silver nanoparticles were synthesized using A. bracteosa extract and were confirmed by UV-Vis spectrophotometer, Scanning Electron Microscope (SEM) and Fourier Transform Infrared Spectroscopy (FTIR). The antibacterial, anti-biofilm, cell proliferation inhibition, TLC-Bioautography, TLC-Spot screening, antioxidant, and phytochemical screening were also investigated. RESULTS UV-Vis spectrum and Scanning electron microscopy confirmed the synthesis of green nanoparticles at 400 nm with tube-like structures. FTIR spectrum showed that functional groups of nanoparticles have a role in capping and stability of AgNP. Agar well diffusion assay represented the maximum antibacterial effect of ABAgNPs against Escherichia coli, Klebsiella pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, and Pseudomonas aeruginosa at 0.10 g/mL concentration compared to ABaqu. Two types of interactions among nanoparticles, aqueous extract, and antibiotics (Synergistic and additive) were recorded against tested pathogens. Crystal violet, MTT, TLC-bio-autography, and spot screening supported the findings of the antibacterial assay. Highest antioxidant potential effect in ABaqu was 14.62% (DPPH) and 13.64% (ABTS) while 4.85% (DPPH) and 4.86% (ABTS) was recorded in ABAgNPs. Presence of phytochemical constituents showed pharmacological importance. CONCLUSION It was concluded that green synthesis is an innovative technology in which natural products are conjugated with metallic particles and are used against infectious pathogens. The current research showed the significant use of green nanoparticles against etiological agents.
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Affiliation(s)
- Sadia Nazer
- Microbial Biotechnology Laboratory, Department of Zoology, University of Azad Jammu and Kashmir, Muzaffarabad, 13100, Pakistan
| | - Saiqa Andleeb
- Microbial Biotechnology Laboratory, Department of Zoology, University of Azad Jammu and Kashmir, Muzaffarabad, 13100, Pakistan
| | - Shaukat Ali
- Department of Zoology, GC University, Lahore, Pakistan
| | - Nazia Gulzar
- Microbial Biotechnology Laboratory, Department of Zoology, University of Azad Jammu and Kashmir, Muzaffarabad, 13100, Pakistan
| | - Tariq Iqbal
- Department of Physics, University of Azad Jammu and Kashmir, Muzaffarabad, 13100, Pakistan
| | - Muhammad A R Khan
- Department of Physics, University of Azad Jammu and Kashmir, Muzaffarabad, 13100, Pakistan
| | - Abida Raza
- National Institute for Lasers and Optronics (NILOP), Pakistan Atomic Energy Commission, Islamabad, Pakistan
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Cao X, DeLoid GM, Bitounis D, De La Torre-Roche R, White JC, Zhang Z, Ho CG, Ng KW, Eitzer BD, Demokritou P. Co-exposure to the food additives SiO 2 (E551) or TiO 2 (E171) and the pesticide boscalid increases cytotoxicity and bioavailability of the pesticide in a tri-culture small intestinal epithelium model: Potential health implications. ENVIRONMENTAL SCIENCE. NANO 2019; 6:2786-2800. [PMID: 32133147 PMCID: PMC7055717 DOI: 10.1039/c9en00676a] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/20/2023]
Abstract
Many toxicity investigations have evaluated the potential health risks of ingested engineered nanomaterials (iENMs); however, few have addressed the potential combined effects of iENMs and other toxic compounds (e.g. pesticides) in food. To address this knowledge gap, we investigated the effects of two widely used, partly nanoscale, engineered particulate food additives, TiO2 (E171) and SiO2 (E551), on the cytotoxicity and cellular uptake and translocation of the pesticide boscalid. Fasting food model (phosphate buffer) containing iENM (1% w/w), boscalid (10 or 150 ppm), or both, was processed using a simulated in vitro oral-gastric-small intestinal digestion system. The resulting small intestinal digesta was applied to an in vitro tri-culture small intestinal epithelium model, and effects on cell layer integrity, viability, cytotoxicity and production of reactive oxygen species (ROS) were assessed. Boscalid uptake and translocation was also quantified by LC/MS. Cytotoxicity and ROS production in cells exposed to combined iENM and boscalid were greater than in cells exposed to either iENM or boscalid alone. More importantly, translocation of boscalid across the tri-culture cellular layer was increased by 20% and 30% in the presence of TiO2 and SiO2, respectively. One possible mechanism for this increase is diminished epithelial cell health, as indicated by the elevated oxidative stress and cytotoxicity observed in co-exposed cells. In addition, analysis of boscalid in digesta supernatants revealed 16% and 30% more boscalid in supernatants from samples containing TiO2 and SiO2, respectively, suggesting that displacement of boscalid from flocculated digestive proteins by iENMs may also contribute to the increased translocation.
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Affiliation(s)
- Xiaoqiong Cao
- Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA
| | - Glen M. DeLoid
- Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA
| | - Dimitrios Bitounis
- Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA
| | - Roberto De La Torre-Roche
- Department of Analytical Chemistry, Connecticut Agricultural Experiment Station, New Haven, CT 06504, USA
| | - Jason C. White
- Department of Analytical Chemistry, Connecticut Agricultural Experiment Station, New Haven, CT 06504, USA
| | - Zhenyuan Zhang
- Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA
| | - Chin Guan Ho
- School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798
| | - Kee Woei Ng
- Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA
- School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798
- Environmental Chemistry and Materials Centre, Nanyang Environment & Water Research Institute, CleanTech One, Singapore 637141
| | - Brian D. Eitzer
- Department of Analytical Chemistry, Connecticut Agricultural Experiment Station, New Haven, CT 06504, USA
| | - Philip Demokritou
- Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA
- School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798
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50
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Hu M, Jovanović B, Palić D. In silico prediction of MicroRNA role in regulation of Zebrafish (Danio rerio) responses to nanoparticle exposure. Toxicol In Vitro 2019; 60:187-202. [PMID: 31132477 DOI: 10.1016/j.tiv.2019.05.014] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2018] [Revised: 03/05/2019] [Accepted: 05/19/2019] [Indexed: 12/13/2022]
Abstract
The release of nanoparticles to the environment can affect health of the exposed organisms. MicroRNAs have been suggested as potential toxicology biomarkers, however the information about use of microRNA in aquatic organisms exposed to nanoparticles (NP) is limited. In silico analysis from publicly available gene expression data was performed. Data selection for the analysis was based on reported biological and pathological outcomes of NP induced toxicity in zebrafish. After identifying relevant genes, we constructed six miRNA-mRNA regulatory networks involved in nanoparticle induced toxicological responses in zebrafish. Based on our prediction and selection criteria we selected six miRNAs that overlapped in constructed networks with remarkable prediction score, and were validated by previous mammalian and zebrafish microRNA profiling studies: dre-miR-124, -144, -148, -155, -19a, -223. The results of this in silico analysis indicate that several highly conserved miRNAs likely have a regulatory role of organismal responses to nanoparticles, and can possibly be used as biomarkers of nanotoxicity in studies using zebrafish as model organism One health approaches.
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Affiliation(s)
- Moyan Hu
- Chair for Fish Diseases and Fisheries Biology, Faculty of Veterinary Medicine, Ludwig Maximilian University of Munich, Munich, Germany
| | - Boris Jovanović
- Department of Natural Resources Ecology and Management, Iowa State University, Ames, IA, USA
| | - Dušan Palić
- Chair for Fish Diseases and Fisheries Biology, Faculty of Veterinary Medicine, Ludwig Maximilian University of Munich, Munich, Germany.
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