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Hara MA, Ramadan M, Abdelhameid MK, Taher ES, Mohamed KO. Pyroptosis and chemical classification of pyroptotic agents. Mol Divers 2025; 29:2765-2782. [PMID: 39316325 PMCID: PMC12081555 DOI: 10.1007/s11030-024-10987-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2024] [Accepted: 09/03/2024] [Indexed: 09/25/2024]
Abstract
Pyroptosis, as a lytic-inflammatory type of programmed cell death, has garnered considerable attention due to its role in cancer chemotherapy and many inflammatory diseases. This review will discuss the biochemical classification of pyroptotic inducers according to their chemical structure, pyroptotic mechanism, and cancer type of these targets. A structure-activity relationship study on pyroptotic inducers is revealed based on the surveyed pyroptotic inducer chemotherapeutics. The shared features in the chemical structures of current pyroptotic inducer agents were displayed, including an essential cyclic head, a vital linker, and a hydrophilic tail that is significant for π-π interactions and hydrogen bonding. The presented structural features will open the way to design new hybridized classes or scaffolds as potent pyroptotic inducers in the future, which may represent a solution to the apoptotic-resistance dilemma along with synergistic chemotherapeutic advantage.
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Affiliation(s)
- Mohammed A Hara
- Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Al Azhar University (Assiut), Assiut, 71524, Egypt
| | - Mohamed Ramadan
- Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Al Azhar University (Assiut), Assiut, 71524, Egypt.
| | - Mohammed K Abdelhameid
- Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Ehab S Taher
- Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Al Azhar University (Assiut), Assiut, 71524, Egypt
- Department of Basic Medical and Dental Sciences, Faculty of Dentistry, Zarqa University, Zarqa, Jordan
| | - Khaled O Mohamed
- Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt
- Pharmaceutical Chemistry Department, Faculty of Pharmacy, Sinai University (Arish Branch), ElArich, Egypt
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2
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Aschner M, Skalny AV, Martins AC, Tizabi Y, Zaitseva IP, Santamaria A, Lu R, Gluhcheva YY, Tinkov AA. The role of NLRP3 inflammasome activation in proinflammatory and cytotoxic effects of metal nanoparticles. Arch Toxicol 2025; 99:1287-1314. [PMID: 39960653 DOI: 10.1007/s00204-025-03972-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Accepted: 01/27/2025] [Indexed: 04/04/2025]
Abstract
Exposure to metal nanoparticles (NPs) is known to induce inflammatory responses in various tissues, thus limiting their therapeutic potential. NOD-like receptor protein 3 (NLRP3) inflammasome activation is an essential component of innate immunity playing a significant role in inflammation and development of inflammatory diseases. Therefore, the objective of the present review was to summarize data on the role of NLRP3 inflammasome in proinflammatory effects induced by metal NPs, and to discuss the underlying molecular mechanisms, including its dependence on the physical and chemical properties of metal NPs. Titanium, zinc, silver, aluminum, iron, cobalt, nickel, vanadium, and tungsten nanoparticles, as well as metal-based quantum dots have all been shown to induce NLRP3 inflammasome activation in vitro in macrophages and monocytes, dendritic cells, keratinocytes, hepatocytes, enterocytes, microglia, astrocytes, lung epithelial cells, endotheliocytes, as well as certain types of cancer cells. In vivo studies confirmed the role of NLRP3 pathway activation in development of colitis, pulmonary inflammation, liver damage, osteolysis, and neuroinflammation induced by various metal nanoparticles. Briefly, particle endocytosis with subsequent lysosomal damage, induction of ROS formation, K+ efflux, increased intracellular Ca2+ levels, and NF-κB pathway activation results in NLRP3 inflammasome complex assembly, caspase-1 activation, and cleavage of pro-IL-1β and pro-IL-18 to mature proinflammatory cytokines, while gasdermin D cleavage induces pyroptotic cell death. Moreover, small-sized and rod-shaped metal NPs exert a more profound stimulatory effect on NLRP3 inflammasome activation, but contrary findings have also been reported. Taken together, it is concluded that NLRP3 inflammasome may mediate both adverse proinflammatory effects of metal nanoparticles, as well as their beneficial effect when used as antitumor agents.
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Affiliation(s)
- Michael Aschner
- Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
| | - Anatoly V Skalny
- Institute of Bioelementology, Orenburg State University, Orenburg, 460018, Russia
- Center of Bioelementology and Human Ecology, IM Sechenov First Moscow State Medical University (Sechenov University), Moscow, 119146, Russia
| | - Airton C Martins
- Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA
| | - Yousef Tizabi
- Department of Pharmacology, Howard University College of Medicine, Washington, DC, 20059, USA
| | - Irina P Zaitseva
- Laboratory of Ecobiomonitoring and Quality Control and Department of Physical Education, Yaroslavl State University, Yaroslavl, 150003, Russia
| | - Abel Santamaria
- Facultad de Ciencias, Universidad Nacional Autónoma de México, 04510, Mexico City, Mexico
- Laboratorio de Nanotecnología y Nanomedicina, Departamento de Atención a la Salud, Universidad Autónoma Metropolitana-Xochimilco, 04960, Mexico City, Mexico
| | - Rongzhu Lu
- Department of Preventive Medicine and Public Health Laboratory Science, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, People's Republic of China
| | - Yordanka Y Gluhcheva
- Institute of Experimental Morphology, Pathology and Anthropology With Museum, Bulgarian Academy of Sciences, Acad. Georgi Bonchev, Str., Bl. 25, 1113, Sofia, Bulgaria
| | - Alexey A Tinkov
- Institute of Bioelementology, Orenburg State University, Orenburg, 460018, Russia
- Center of Bioelementology and Human Ecology, IM Sechenov First Moscow State Medical University (Sechenov University), Moscow, 119146, Russia
- Laboratory of Ecobiomonitoring and Quality Control and Department of Physical Education, Yaroslavl State University, Yaroslavl, 150003, Russia
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3
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Guo Y, Morshedi M. Cutting-edge nanotechnology: unveiling the role of zinc oxide nanoparticles in combating deadly gastrointestinal tumors. Front Bioeng Biotechnol 2025; 13:1547757. [PMID: 40182988 PMCID: PMC11966175 DOI: 10.3389/fbioe.2025.1547757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Accepted: 02/21/2025] [Indexed: 04/05/2025] Open
Abstract
Zinc oxide nanoparticles (ZnO-NPs) have gained significant attention in cancer therapy due to their unique physical and chemical properties, particularly in treating gastrointestinal (GI) cancers such as gastric, colorectal, and hepatocellular carcinoma. These nanoparticles generate reactive oxygen species (ROS) upon entering cancer cells, causing oxidative stress that leads to cellular damage, DNA fragmentation, and apoptosis. ZnO-NPs affect the expression of key proteins involved in apoptosis, including p53, Bax, and Bcl-2, which regulate cell cycle arrest and programmed cell death. Additionally, ZnO-NPs can reduce mitochondrial membrane potential, further enhancing apoptosis in cancer cells. Furthermore, ZnO-NPs inhibit cancer cell proliferation by interfering with cell cycle progression. They reduce levels of cyclins and cyclin-dependent kinases (CDKs), leading to cell cycle arrest. ZnO-NPs also exhibit anti-metastatic properties by inhibiting the migration and invasion of cancer cells through modulation of signaling pathways that affect cell adhesion and cytoskeletal dynamics. The efficacy of ZnO-NPs in overcoming chemotherapy resistance has been demonstrated by their ability to reduce the IC50 values of chemotherapeutic agents, making cancer cells more susceptible to drug-induced cell death. In this review, we summarize the mechanisms by which ZnO-NPs exert anticancer effects in GI cancers, focusing on apoptosis, cell cycle regulation, and metastasis inhibition, while also highlighting the current limitations in translating these findings into effective clinical treatments.
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Affiliation(s)
- Yonggang Guo
- Pingdingshan College, Pingdingshan, Henan, China
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Wu J, Liu Z, Wang L, Pei Z, Han Z, Cui X, Pan X, Cao J, Huang Y, Sun S, Wang J, Cheng C, Cheng L. Hydrotalcites-Induced Pyroptosis Combined with Toll-Like Receptor Activation Elicited Dual Stimulation of Innate and Adaptive Immunity. ACS NANO 2025; 19:8070-8084. [PMID: 39964224 DOI: 10.1021/acsnano.4c16281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/05/2025]
Abstract
Increasing evidence illustrates the significance of promoting tumor immunogenicity and an efficient immune response in immunotherapy, but the immunosuppressive tumor microenvironment (TME) remains an obstacle. Herein, AlZn hydrotalcite (AZOH) was synthesized as a pyroptosis inducer and further loaded with R848 to formulate R@AZOH. R@AZOH efficiently triggered CT26 cell pyroptosis through Zn2+ overload-evoked mitochondrial dysfunction and its downstream caspase-1/GSDMD pathway, resulting in the release of inflammatory cytokines, membrane fracture, and immunogenic cell death (ICD). Moreover, R@AZOH served as antigen traps to facilitate antigen presentation, thereby cooperating with TLR activation to dually stimulate dendritic cells (DCs). The combination of R@AZOH rapidly initiated innate immunity and prolonged the adaptive immune response, resulting in the suppression of tumor growth, immune cell activation and a "hot" tumor niche. The potent antitumor immunity was further enhanced by combination with an immune checkpoint inhibitor (αCTLA-4), which inhibited both primary and distant tumors, as well as systemic immune activation. Astonishingly, we also explored the potential application of R@AZOH as a tumor vaccine adjuvant and demonstrated its ability to elicit immunological memory to prevent tumor growth in an orthotopic melanoma model. Overall, our work emphasized the potential application of combining pyroptosis and TLR activation to stimulate both innate and adaptive immunity to overcome the immunosuppressive TME and presented a good adjuvant candidate.
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Affiliation(s)
- Jie Wu
- School of Pharmacy, Faculty of Medicine, Macau University of Science and Technology, Taipa, Macau SAR 999078, China
- Macao Institute of Materials Science and Engineering, Macau University of Science and Technology, Taipa, Macau SAR 999078, China
- Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, China
| | - Zhicheng Liu
- Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, China
| | - Li Wang
- Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, China
| | - Zifan Pei
- Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, China
| | - Zhihui Han
- Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, China
| | - Xiaoliang Cui
- Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, China
| | - Xiaoxiao Pan
- Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, China
| | - Jie Cao
- Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, China
| | - Yechen Huang
- Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, China
| | - Shumin Sun
- Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, China
| | - Jianman Wang
- School of Pharmacy, Faculty of Medicine, Macau University of Science and Technology, Taipa, Macau SAR 999078, China
| | - Chong Cheng
- College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China
| | - Liang Cheng
- School of Pharmacy, Faculty of Medicine, Macau University of Science and Technology, Taipa, Macau SAR 999078, China
- Macao Institute of Materials Science and Engineering, Macau University of Science and Technology, Taipa, Macau SAR 999078, China
- Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, China
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Pei X, Ma S, Hong L, Zuo Z, Xu G, Chen C, Shen Y, Liu D, Li C, Li D. Molecular insights of T-2 toxin exposure-induced neurotoxicity and the neuroprotective effect of dimethyl fumarate. Food Chem Toxicol 2025; 196:115166. [PMID: 39617286 DOI: 10.1016/j.fct.2024.115166] [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: 10/27/2024] [Revised: 11/24/2024] [Accepted: 11/28/2024] [Indexed: 12/06/2024]
Abstract
T-2 toxin, a potent environmental pollutant, has been proved to stimulate neuroinflammation, while the connection between T-2 toxin and pyroptosis remain elusive. Dimethyl fumarate (DMF), recently identified as a neuroprotectant and pyroptosis inhibitor, has potential therapeutic applications that are underexplored. Based on present study in vitro and vivo, we demonstrated that T-2 toxin induced the activation of NLRP3-Caspase-1 inflammasome in hippocampal neurons. In addition to proinflammatory mediator overexpression, gasdermin D (GSDMD)-dependently pyroptosis in the mouse hippocampal neuron cell line (HT22) treated by T-2 toxin was determined in our study. Moreover, the palliative effect of knockdown sequence of high mobility group B1 protein (HMGB1) provided more details for T-2 toxin-initiated pyroptosis. Importantly, we confirmed that DMF, as a novel inhibitor of GSDMD, could alleviate pyroptosis induced by T-2 toxin in an GSDMD targeting manner. In summary, our studies exposed the evidence that T-2 toxin could induce NLRP3 inflammasome activation and hippocampal neuronal pyroptosis. More notably, DMF was turn out to be a critical executioner for attenuating GSDMD-mediated pyroptosis. Our data found a new function of DMF and suggested a novel therapy strategy against mycotoxin-triggered neuronal inflammation, which leads to varieties of neurological diseases.
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Affiliation(s)
- Xingyao Pei
- Open Fund of Key Laboratory of Smart Breeding (Co-construction By Ministry and Province), Ministry of Agriculture and Rural Affairs, Tianjin Agricultural University, Jinjing Road No.22, Xiqing District, Tianjin 300392, China; Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Jinjing Road No.22, Xiqing District, Tianjin 300392, China
| | - Shuhui Ma
- Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Jinjing Road No.22, Xiqing District, Tianjin 300392, China
| | - Liang Hong
- Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Jinjing Road No.22, Xiqing District, Tianjin 300392, China
| | - Zonghui Zuo
- Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Jinjing Road No.22, Xiqing District, Tianjin 300392, China
| | - Gang Xu
- Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Jinjing Road No.22, Xiqing District, Tianjin 300392, China
| | - Chun Chen
- Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Jinjing Road No.22, Xiqing District, Tianjin 300392, China
| | - Yao Shen
- Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Jinjing Road No.22, Xiqing District, Tianjin 300392, China
| | - Dingkuo Liu
- Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Jinjing Road No.22, Xiqing District, Tianjin 300392, China; Tianjin Key Laboratory of Biological Feed Additive Enterprise, S&E Burgeoning Biotechnology (Tianjin) Co., Ltd, Tianjin 300383, China
| | - Cun Li
- Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Jinjing Road No.22, Xiqing District, Tianjin 300392, China
| | - Daowen Li
- Open Fund of Key Laboratory of Smart Breeding (Co-construction By Ministry and Province), Ministry of Agriculture and Rural Affairs, Tianjin Agricultural University, Jinjing Road No.22, Xiqing District, Tianjin 300392, China; Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Jinjing Road No.22, Xiqing District, Tianjin 300392, China; Tianjin Key Laboratory of Biological Feed Additive Enterprise, S&E Burgeoning Biotechnology (Tianjin) Co., Ltd, Tianjin 300383, China.
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Hussain R, Naz S, Alam S, Ali HM, Ali A, Khan MS, Fouad D, Ataya FS, Mammadov A, Li K. Temporal and dosage impact of magnesium oxide nanoparticles on grass carp: unveiling oxidative stress, DNA damage, and antioxidant suppression. Toxicol Mech Methods 2025; 35:19-31. [PMID: 39034674 DOI: 10.1080/15376516.2024.2382801] [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: 05/18/2024] [Revised: 07/15/2024] [Accepted: 07/16/2024] [Indexed: 07/23/2024]
Abstract
Magnesium oxide nanoparticles (MgO NPs) have gained significant importance in biomedicine and variety of nanotechnology-based materials used in the agriculture and biomedical industries. However, the release of different nanowastes in the water ecosystem becomes a serious concern. Therefore, this study was executed to evaluate the toxic impacts of MgO NPs on grass carp. A total of 60 grass carp were randomly divided in three groups (G0, G1, and G2). Fish reared in group G0 were kept as control while fish of groups G1 and G2 were exposed to 0.5 mg/L and 0.7 mg/L MgO NPs, respectively, mixed in water for 21 days. The 96h median lethal concentration (LC50) of MgO NPs was found to be 4.5 mg/L. Evaluation of oxidative stress biomarkers, antioxidant enzymes, DNA damage in different visceral organs and the presence of micronuclei in erythrocytes were determined on days 7, 14, and 21 of the trial. Results revealed dose- and time-dependent significantly increased values of reactive oxygen species, lipid peroxidation product, DNA damage in multiple visceral organs and formation of micronuclei in the erythrocytes of treated fish (0.7 mg/L). The results on antioxidant profile exhibited significantly lower amounts of total proteins, catalase, superoxide dismutase, and peroxidase in visceral organs of the fish exposed to MgO NPs (0.5 and 0.7 mg/L) at day 21 of trial compared to control group. In conclusion, it has been recorded that MgO NPs severely influence the normal physiological functions of the grass carp even at low doses.
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Affiliation(s)
- Riaz Hussain
- Faculty of Veterinary and Animal Sciences, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
| | - Saima Naz
- Department of Zoology, Government Sadiq College Women University, Bahawalpur, Pakistan
| | - Sana Alam
- Department of Zoology, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
| | - Hafiz Muhammad Ali
- Faculty of Veterinary and Animal Sciences, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
| | - Arooj Ali
- Faculty of Physical & Mathematical Sciences Institute of Physics, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
| | - Muhammad Shahid Khan
- Faculty of Physical & Mathematical Sciences Institute of Physics, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
| | - Dalia Fouad
- Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Farid Shokry Ataya
- Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Ayaz Mammadov
- Department of Life Sciences, Western Caspian University, Baku, Azerbaijan
| | - Kun Li
- College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China
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Gökmen GG, Mirsafi FS, Leißner T, Akan T, Mishra YK, Kışla D. Zinc oxide nanomaterials: Safeguarding food quality and sustainability. Compr Rev Food Sci Food Saf 2024; 23:e70051. [PMID: 39530622 DOI: 10.1111/1541-4337.70051] [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: 06/17/2024] [Revised: 09/17/2024] [Accepted: 10/08/2024] [Indexed: 11/16/2024]
Abstract
In this era, where food safety and sustainability are paramount concerns, the utilization of zinc oxide (ZnO) nanoparticles (NPs) is a promising solution to enhance the safety, quality, and sustainability of food products. ZnO NPs in the food industry have evolved significantly over time, reflecting advancements in synthesizing methods, antimicrobial activities, and risk assessment considerations for human health and the environment. This comprehensive review delves into the historical trajectory, current applications, and prospects of ZnO NPs in food-related contexts. Synthesizing methods, ranging from solvothermal and solgel techniques to laser ablation and microfluidic reactors, have facilitated the production of ZnO NPs with tailored properties suited for diverse food applications. The remarkable antimicrobial activity of ZnO NPs against a wide spectrum of pathogens has garnered attention for their potential to enhance food safety and extend shelf-life. Furthermore, comprehensive risk assessment methodologies have been employed to evaluate the potential impacts of ZnO NPs on human health and the environment, regarding toxicity, migration, and ecological implications. By navigating the intricate interplay between synthesis methods, antimicrobial efficacy, inhibitory mechanisms, and risk assessment protocols, by elucidating the multifaceted role of ZnO NPs in shaping the past, present, and future of the food industry, this review offers valuable insights and promising avenues for researchers, policymakers, and industry stakeholders to enhance food safety, quality, and sustainability.
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Affiliation(s)
- Gökhan Gurur Gökmen
- Department of Food Engineering, Faculty of Engineering, Ege University, Izmir, Bornova, Turkey
| | - Fatemeh Sadat Mirsafi
- Smart Materials, NanoSYD, Mads Clausen Institute, University of Southern Denmark, Sønderborg, Denmark
| | - Till Leißner
- Smart Materials, NanoSYD, Mads Clausen Institute, University of Southern Denmark, Sønderborg, Denmark
| | - Tamer Akan
- Department of Physics, Faculty of Science, Eskisehir Osmangazi University, Eskisehir, Odunpazarı, Turkey
| | - Yogendra Kumar Mishra
- Smart Materials, NanoSYD, Mads Clausen Institute, University of Southern Denmark, Sønderborg, Denmark
| | - Duygu Kışla
- Department of Food Engineering, Faculty of Engineering, Ege University, Izmir, Bornova, Turkey
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Yu T, Deng X, Yang X, Yin Y, Liu Y, Xu S. New insights into evodiamine attenuates IPEC-J2 cells pyroptosis induced by T-2 toxin - Activating Keap1-Nrf2/NF-κB signaling pathway through binding with Keap1. JOURNAL OF ENVIRONMENTAL MANAGEMENT 2024; 370:122605. [PMID: 39305878 DOI: 10.1016/j.jenvman.2024.122605] [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: 07/16/2024] [Revised: 08/30/2024] [Accepted: 09/17/2024] [Indexed: 11/17/2024]
Abstract
T-2 toxin (T-2) is a highly toxic mycotoxin with a molecular weight of 466.52 g/mol. Evodiamine (EV), an alkaloid component of Evodia, has anti-inflammation and antioxidant properties. As a receptor of oxidative stress, Keap1 with a molecular weight of 70 kDa, is a molecular switch that controls the Nrf2 signaling pathway. In this paper, the effect of EV on Keap1-Nrf2/NF-κB pathway was investigated. Based on our research outcomes, it was observed that T-2 exposure substantially increased IPEC-J2 cells intracellular ROS levels and MDA accumulation, decreased SOD and CAT activities, disrupted intestinal tight junction (ZO-1, occludin, and claudin-1), and up-regulated pyroptosis-related protein (ASC, NLRP3, caspase-1, GSDMD, IL-1β, and IL-18). Additionally, EV could bind well with Keap1, the separating it from Nrf2, promoting Nrf2 into the nucleus, enhanced antioxidant enzyme activities, reduced the production of ROS, down-regulated NF-κB expression, alleviated T-2-induced pyroptosis, and restored tight junction protein expression. However, after treatment with the Nrf2 inhibitor ML385, ML385 reversed the protective effect of EV on IPEC-J2 cells. Collectively, EV can activate the Keap1-Nrf2/NF-κB signaling pathway via binding to Keap1, exert anti-inflammatory and antioxidant effects, inhibit the pyroptosis of IPEC-J2 cells triggered by T-2, and retore intestinal barrier function.
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Affiliation(s)
- Tingting Yu
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China
| | - Xinrui Deng
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China
| | - Xuejiao Yang
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China
| | - Yilin Yin
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China
| | - Yong Liu
- Mudanjiang Medical University, Mudanjiang, 157011, PR China.
| | - Shiwen Xu
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China.
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Hassan MH, Emam IA, Farghali H, Ibrahim MA, Hassan NH, Farroh KY, Hassanen EI. Toxicological screening of zinc oxide nanoparticles in mongrel dogs after seven days of repeated subcutaneous injections. BMC Vet Res 2024; 20:476. [PMID: 39425163 PMCID: PMC11487719 DOI: 10.1186/s12917-024-04268-5] [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: 06/13/2024] [Accepted: 09/04/2024] [Indexed: 10/21/2024] Open
Abstract
Zinc oxide nanoparticles (ZnO NPs) have recently been applied in various veterinary and medical fields, however, the toxicological evaluations of these NPs in dogs are lacking. Therefore, the current study is designed to assess the impact of exposure to daily subcutaneous (SC) injections of ZnO NPs at different concentrations on various organs of mongrel dogs. Nine dogs were randomly divided into three groups (n = 3 for each) as follows: group (1) served as the control group, whereas groups (2&3) received SC injections of 50 and 100 ppm ZnO NPs (8 and 16 μg/kg bwt), respectively, once/day for 7 days. Our results revealed that ZnO NPs disrupted the oxidant/antioxidant balance in the lungs, liver, and kidneys of dogs in a dose-dependent manner. ZnO NPs induced dose-dependent radiological, ultrasonographical, and histopathological alterations in various organs especially lungs, spleen, liver, and kidneys along with disturbance in both liver and kidney biomarkers levels. Most organs of both ZnO NPs receiving groups displayed strong caspase-3 protein expression. Additionally, it upregulates the transcriptase levels of TNF-α and VEGF, as well as downregulates the antiapoptotic gene IL-10 in lung, kidney, and liver tissue homogenates. It was concluded that the daily SC injections of dogs with ZnO NPs at concentrations of 50 and 100 ppm caused extensive oxidative stress damage in various organs which provoked serious pathological processes such as apoptosis and inflammation.
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Affiliation(s)
- Marwa H Hassan
- Department of Veterinary Clinical Sciences, Faculty of Veterinary Medicine, Jordan University of Science and Technology, Irbid, Jordan
- Department of Surgery, Anesthesiology and Radiology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
| | - Ibrahim A Emam
- Department of Surgery, Anesthesiology and Radiology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
| | - Haitham Farghali
- Department of Surgery, Anesthesiology and Radiology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
| | - Marwa A Ibrahim
- Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
| | - Neven H Hassan
- Department of Physiology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
| | - Khaled Y Farroh
- Nanotechnology and Advanced Materials Central Lab, Agricultural Research Center, Giza, Egypt
| | - Eman I Hassanen
- Department of Pathology, Faculty of Veterinary Medicine, Cairo University, P.O. Box 12211, Giza, Egypt.
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Ren S, Liang P, Feng R, Yang W, Qiu T, Zhang J, Li Q, Yang G, Sun X, Yao X. The phosphorylation of Smad3 by CaMKIIγ leads to the hepatocyte pyroptosis under perfluorooctane sulfonate exposure. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2024; 284:116924. [PMID: 39181077 DOI: 10.1016/j.ecoenv.2024.116924] [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: 08/13/2024] [Accepted: 08/21/2024] [Indexed: 08/27/2024]
Abstract
Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant and accumulated in the liver of mammals. PFOS exposure is closely associated with the development of pyroptosis. Nevertheless, the underlying mechanism is unclear. We found here that PFOS induced pyroptosis in the mice liver and L-02 cells as demonstrated by activation of the NOD-like receptor protein 3 inflammasome, gasdermin D cleavage and increased release of interleukin-1β and interleukin-18. The level of cytoplasmic calcium was accelerated in hepatocytes upon exposure to PFOS. The phosphorylated/activated form of calcium/calmodulin-dependent protein kinase II (CaMKII) was augmented by PFOS in vivo and in vitro. PFOS-induced pyroptosis was relieved by CaMKII inhibitor. Among various CaMKII subtypes, we identified that CaMKIIγ was activated specifically by PFOS. CaMKIIγ interacted with Smad family member 3 (Smad3) under PFOS exposure. PFOS increased the phosphorylation of Smad3, and CaMKII inhibitor or CaMKIIγ siRNA alleviated PFOS-caused phosphorylation of Smad3. Inhibiting Smad3 activity was found to alleviate PFOS-induced hepatocyte pyroptosis. This study puts forward that CaMKIIγ-Smad3 is the linkage between calcium homeostasis disturbance and pyroptosis, providing a mechanistic explanation for PFOS-induced pyroptosis.
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Affiliation(s)
- Siyu Ren
- Department of Occupation and Environment Health, Dalian Medical University, 9 Lvshun South Road, Dalian, China
| | - Peiyao Liang
- Department of Occupation and Environment Health, Dalian Medical University, 9 Lvshun South Road, Dalian, China
| | - Ruzhen Feng
- Department of Occupation and Environment Health, Dalian Medical University, 9 Lvshun South Road, Dalian, China
| | - Wei Yang
- Department of Occupation and Environment Health, Dalian Medical University, 9 Lvshun South Road, Dalian, China
| | - Tianming Qiu
- Department of Occupation and Environment Health, Dalian Medical University, 9 Lvshun South Road, Dalian, China.
| | - Jingyuan Zhang
- Department of Occupation and Environment Health, Dalian Medical University, 9 Lvshun South Road, Dalian, China
| | - Qiujuan Li
- Department of Nutrition, Dalian Medical University, 9 Lvshun South Road, Dalian, China
| | - Guang Yang
- Department of Nutrition, Dalian Medical University, 9 Lvshun South Road, Dalian, China
| | - Xiance Sun
- Department of Occupation and Environment Health, Dalian Medical University, 9 Lvshun South Road, Dalian, China
| | - Xiaofeng Yao
- Department of Occupation and Environment Health, Dalian Medical University, 9 Lvshun South Road, Dalian, China.
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11
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Wang L, Zheng G, Wang P, Jia X. Unlocking the secrets of NPSLE: the role of dendritic cell-secreted CCL2 in blood-brain barrier disruption. Front Immunol 2024; 15:1343805. [PMID: 39403387 PMCID: PMC11472714 DOI: 10.3389/fimmu.2024.1343805] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Accepted: 05/27/2024] [Indexed: 11/02/2024] Open
Abstract
Background This study employed RNA-seq technology and meta-analysis to unveil the molecular mechanisms of neuropsychiatric systemic lupus erythematosus (NPSLE) within the central nervous system. Methods Downloaded transcriptomic data on systemic lupus erythematosus (SLE) from the Gene Expression Omnibus (GEO) and analyzed differential genes in peripheral blood samples of NPSLE patients and healthy individuals. Employed WGCNA to identify key genes related to cognitive impairment and validated findings via RNA-seq. Conducted GO, KEGG, and GSEA analyses, and integrated PPI networks to explore gene regulatory mechanisms. Assessed gene impacts on dendritic cells and blood-brain barrier using RT-qPCR, ELISA, and in vitro models. Results Public databases and RNA-seq data have revealed a significant upregulation of CCL2 (C-C motif chemokine ligand 2) in the peripheral blood of both SLE and NPSLE patients, primarily secreted by mature dendritic cells. Furthermore, the secretion of CCL2 by mature dendritic cells may act through the RSAD2-ISG15 axis and is associated with the activation of the NLRs (Nod Like Receptor Signaling Pathway) signaling pathway in vascular endothelial cells. Subsequent in vitro cell experiments confirmed the high expression of CCL2 in peripheral blood dendritic cells of NPSLE patients, with its secretion being regulated by the RSAD2-ISG15 axis and inducing vascular endothelial cell pyroptosis through the activation of the NLRs signaling pathway. Clinical trial results ultimately confirmed that NPSLE patients exhibiting elevated CCL2 expression also experienced cognitive decline. Conclusions The secretion of CCL2 by dendritic cells induces pyroptosis in vascular endothelial cells, thereby promoting blood-brain barrier damage and triggering cognitive impairment in patients with systemic lupus erythematosus.
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Affiliation(s)
- Lei Wang
- Department of Medical Imaging, Hebei General Hospital, Shijiazhuang, China
| | - Guimin Zheng
- Department of Rheumatology and Immunology, Hebei General Hospital, Shijiazhuang, China
| | - Peiwen Wang
- 3 Major Classes of Clinical Medicine Department, Grade 2021, Hebei Medical University, Shijiazhuang, China
| | - Xiuchuan Jia
- Department of Medical Imaging, Hebei General Hospital, Shijiazhuang, China
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12
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Zhu Z, Zhang Y, Wang R, Dong Y, Wu J, Shao L. Zinc oxide nanoparticles disrupt the mammary epithelial barrier via Z-DNA binding protein 1-triggered PANoptosis. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2024; 283:116777. [PMID: 39053182 DOI: 10.1016/j.ecoenv.2024.116777] [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: 02/04/2024] [Revised: 07/08/2024] [Accepted: 07/21/2024] [Indexed: 07/27/2024]
Abstract
Lactation women, a highly concerned demographic in society, face health risks that deserve attention. Zinc oxide nanoparticles (ZnO NPs) are widely utilized in food and daily products due to their excellent physicochemical properties, leading to the potential exposure of lactating women to ZnO NPs. Hence, assessing the potential risks associated with ZnO NP exposure during lactation is critical. While studies have confirmed that exposure to ZnO NPs during lactation can induce toxic responses in multiple organs through blood circulation, the effects of lactational exposure on mammary tissue remain unclear. This research investigated the impairment of mammary tissue induced by ZnO NPs and its potential mechanisms. Through administering multiple injections of ZnO NPs into the tail vein of lactating ICR mice, our study revealed that ZnO NPs can deposit in the mammary tissues, downregulating key components of mammary epithelial barrier such as ZO-1, occludin, and claudin-3. In vivo, we also found that ZnO NPs can simultaneously induce apoptosis, necroptosis, and pyroptosis, called PANoptosis. Additionally, using EpH4-Ev cells to simulate an in vitro mammary epithelial barrier model, we observed that ZnO NPs effectively disrupted the integrity of mammary epithelial barrier and induced PANoptosis. Furthermore, we confirmed that PANoptosis was responsible for the mammary epithelial barrier disruption induced by ZnO NPs. Moreover, we identified that ZBP1 was the primary mechanism of ZnO NPs inducing PANoptosis. These discoveries are designed to enhance our comprehension of the mechanisms underlying mammary epithelial barrier disruption caused by ZnO NPs, and we aim to highlight the potential hazards associated with daily usage and therapeutic exposure to ZnO NPs during lactation.
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Affiliation(s)
- Zhenjun Zhu
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou 510280, China
| | - Yaqing Zhang
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou 510280, China
| | - Ruomeng Wang
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou 510280, China
| | - Yijia Dong
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou 510280, China
| | - Junrong Wu
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou 510280, China.
| | - Longquan Shao
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou 510280, China.
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13
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Li Z, Xu T, Chen H, Wang X. Microglial activation and pyroptosis induced by nano-TiO 2 in marine medaka brain. AQUATIC TOXICOLOGY (AMSTERDAM, NETHERLANDS) 2024; 274:107034. [PMID: 39163698 DOI: 10.1016/j.aquatox.2024.107034] [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: 01/17/2024] [Revised: 07/29/2024] [Accepted: 07/30/2024] [Indexed: 08/22/2024]
Abstract
Recently, nano-titanium dioxide (nano-TiO2) has been widely distributed over surface water. However, there are few reports on its effects on the central nervous system of fish. In this study, we investigated whether nano-TiO2 enters the medaka brain after exposure and its effect on the brain. Marine medaka brains were examined after exposure to 0.01 g/L nano-TiO2 for 3, 10, and 20 d. Nano-TiO2-like particles were found in the telencephalon of treated fish. There was no obvious brain histopathological injury. The number of irregular mitochondria with absent cristae increased. Gene expression of the apoptosis-related genes, casp8, bcl2b, and bax, decreased significantly in the nano-TiO2 group at 3 d. In contrast, the pyroptosis-related genes, gsdmeb and casp1, and inflammation-related factor, il18, increased significantly. As an activated microglia marker, mRNA expression of cd68 increased significantly in the nano-TiO2 treated group. Moreover, CD68 protein expression also increased significantly at 10 d. Altogether, we show that nano-TiO2 can alter mitochondrial morphology in the telencephalon of medaka, leading to microglial activation and pyroptosis.
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Affiliation(s)
- Zirun Li
- National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai, China; Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai, China; International Research Center for Marine Biosciences, Ministry of Science and Technology, Shanghai Ocean University, Shanghai, China
| | - Tao Xu
- National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai, China; Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai, China; International Research Center for Marine Biosciences, Ministry of Science and Technology, Shanghai Ocean University, Shanghai, China
| | - Haijin Chen
- National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai, China; Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai, China; International Research Center for Marine Biosciences, Ministry of Science and Technology, Shanghai Ocean University, Shanghai, China
| | - Xiaojie Wang
- National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai, China; Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai, China; International Research Center for Marine Biosciences, Ministry of Science and Technology, Shanghai Ocean University, Shanghai, China.
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14
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Ansari AA, Lv R, Gai S, Parchur AK, Solanki PR, Archana, Ansari Z, Dhayal M, Yang P, Nazeeruddin M, Tavakoli MM. ZnO nanostructures – Future frontiers in photocatalysis, solar cells, sensing, supercapacitor, fingerprint technologies, toxicity, and clinical diagnostics. Coord Chem Rev 2024; 515:215942. [DOI: 10.1016/j.ccr.2024.215942] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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15
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Ren H, Wu Z, Tan J, Tao H, Zou W, Cao Z, Wen B, Cai Z, Du J, Deng Z. Co-delivery Nano System of MS-275 and V-9302 Induces Pyroptosis and Enhances Anti-Tumor Immunity Against Uveal Melanoma. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2404375. [PMID: 38889339 PMCID: PMC11336933 DOI: 10.1002/advs.202404375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Revised: 06/10/2024] [Indexed: 06/20/2024]
Abstract
In the treatment of uveal melanoma (UVM), histone deacetylase inhibitors (HDACi) have emerged as a promising epigenetic therapy. However, their clinical efficacy is hindered by the suboptimal pharmacokinetics and the strong self-rescue of tumor cells. To overcome these limitations, reactive oxygen species (ROS)-responsive nanoparticles (NPs) are designed that encapsulate HDACi MS-275 and the glutamine metabolism inhibitor V-9302. Upon reaching the tumor microenvironment, these NPs can disintegrate, thereby releasing MS-275 to increase the level of ROS and V-9302 to reduce the production of glutathione (GSH) related to self-rescue. These synergistic effects lead to a lethal ROS storm and induce cell pyroptosis. When combined with programmed cell death protein 1 monoclonal antibodies (α-PD-1), these NPs facilitate immune cell infiltration, improving anti-tumor immunity, converting "immune-cold" tumors into "immune-hot" tumors, and enhancing immune memory in mice. The findings present a nano-delivery strategy for the co-delivery of epigenetic therapeutics and metabolic inhibitors, which induces pyroptosis in tumors cells and improves the effectiveness of chemotherapy and immunotherapy.
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Affiliation(s)
- Hong Ren
- Department of OphthalmologyThe Third Xiangya HospitalCentral South UniversityChangshaHunan410013China
| | - Zhenkai Wu
- Department of OphthalmologyChangde HospitalXiangya School of MedicineCentral South UniversityChangdeHunan415000China
- Department of OphthalmologyThe first people's hospital of Changde cityChangdeHunan415000China
| | - Jia Tan
- Eye Center of Xiangya HospitalCentral South UniversityChangshaHunan410008China
- Hunan Key Laboratory of Ophthalmology and National Clinical Research Center for Geriatric DisordersXiangya HospitalCentral South UniversityChangshaHunan410008China
| | - Hui Tao
- Department of OphthalmologyThe Third Xiangya HospitalCentral South UniversityChangshaHunan410013China
| | - Wangyuan Zou
- Department of AnesthesiologyXiangya HospitalCentral South UniversityChangshaHunan410008China
| | - Zheng Cao
- Department of Chemical and Biomolecular EngineeringUniversity of CaliforniaLos AngelesCA90066USA
| | - Binyu Wen
- Department of OphthalmologyThe Third Xiangya HospitalCentral South UniversityChangshaHunan410013China
| | - Ziyi Cai
- Department of OphthalmologyThe Third Xiangya HospitalCentral South UniversityChangshaHunan410013China
| | - Jiaqi Du
- Department of OphthalmologyThe Third Xiangya HospitalCentral South UniversityChangshaHunan410013China
| | - Zhihong Deng
- Department of OphthalmologyThe Third Xiangya HospitalCentral South UniversityChangshaHunan410013China
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Nasirzadeh N, Monazam Esmaielpour MR, Golbabaei F. The role of submicron zinc oxide particle size in improving UV protection by textiles. INTERNATIONAL JOURNAL OF ENVIRONMENTAL HEALTH RESEARCH 2024; 34:3068-3071. [PMID: 38166475 DOI: 10.1080/09603123.2023.2293063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Accepted: 12/06/2023] [Indexed: 01/04/2024]
Affiliation(s)
- Nafiseh Nasirzadeh
- Occupational Health Engineering, School of Public Health, Department of Occupational Health Engineering, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Monazam Esmaielpour
- Occupational Health Engineering, School of Public Health, Department of Occupational Health Engineering, Tehran University of Medical Sciences, Tehran, Iran
| | - Farideh Golbabaei
- Occupational Health Engineering, School of Public Health, Department of Occupational Health Engineering, Tehran University of Medical Sciences, Tehran, Iran
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17
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Teng J, Yu T, Yan F. GABA attenuates neurotoxicity of zinc oxide nanoparticles due to oxidative stress via DAF-16/FoxO and SKN-1/Nrf2 pathways. THE SCIENCE OF THE TOTAL ENVIRONMENT 2024; 934:173214. [PMID: 38754507 DOI: 10.1016/j.scitotenv.2024.173214] [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: 03/12/2024] [Revised: 04/29/2024] [Accepted: 05/11/2024] [Indexed: 05/18/2024]
Abstract
Zinc oxide nanoparticles (ZnO-NPs) are one of the most widely used metal oxide nanomaterials. The increased use of ZnO-NPs has exacerbated environmental pollution and raised the risk of neurological disorders in organisms through food chains, and it is urgent to look for detoxification strategies. γ-Aminobutyric acid (GABA) is an inhibitory neurotransmitter that has been shown to have anxiolytic, anti-aging and inhibitory effects on nervous system excitability. However, there are few reports on the prevention and control of the toxicity of nano-metal ions by GABA. In zebrafish, ZnO-NPs exposure led to increased mortality and behavioral abnormalities of larva, which could be moderated by GABA intervention. Similar results were investigated in Caenorhabditis elegans, showing lifespan extension, abnormal locomotor frequency and behavior recovery when worms fed with GABA under ZnO-NPs exposure. Moreover, GABA enhanced antioxidant enzyme activities by upregulating the expression of antioxidant-related genes and thus scavenged excessive O2-. In the case of ZnO-NPs exposure, inhibition of nuclear translocation of DAF-16 and SKN-1 was restored by GABA. Meanwhile, the protective effect of GABA was blocked in daf-16 (-) and skn-1 (-) mutant, suggesting that DAF-16/FoxO and SKN-1/Nrf2 pathways is the key targets of GABA. This study provides a new solution for the application of GABA and mitigation of metal nanoparticle neurotoxicity.
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Affiliation(s)
- Jialuo Teng
- Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, China
| | - Ting Yu
- Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, China
| | - Fujie Yan
- Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, China.
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18
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Jiang Y, Geng Y, Gao R, Chen Z, Chen J, Mu X, Zhang Y, Yin X, Chen X, Li F, He J. Maternal exposure to ZIF-8 derails placental function by inducing trophoblast pyroptosis through neutrophils activation in mice. Food Chem Toxicol 2024; 187:114604. [PMID: 38508570 DOI: 10.1016/j.fct.2024.114604] [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: 11/14/2023] [Revised: 03/09/2024] [Accepted: 03/15/2024] [Indexed: 03/22/2024]
Abstract
Adverse environmental factors during maternal gestation pose a threat to pregnancy. Environmental factors, particularly nanoparticles, can impact pregnancy by causing damage to the placenta. Compared to early gestation, foetuses in late gestation are more robustly developed and at lower risk of adverse effects from environmental factors. Delivery systems for targeted therapy during pregnancy is predominantly focused on their application in late gestation. Zeolitic imidazolate framework-8 (ZIF-8) holds great potential for targeted drug therapy. To evaluate the value of ZIF-8 in targeted treatment of disorders associated with late gestation, it is crucial to investigate the biological effects of ZIF-8 exposure during late gestation. Here, a mouse model exposed to ZIF-8 particles at different doses (5, 10, and 15 mg/kg) during late gestation was constructed. We found that ZIF-8 particles were deposited in the uterus of pregnant mice. ZIF-8 could trigger placental neutrophil aggregation and induce inflammation, which led to trophoblast pyroptosis and impair placental function, adversely affecting the foetus. Neutrophil depletion alleviated placental and foetal damage induced by ZIF-8. This study provides a novel mechanistic view of the reproductive toxicity induced by ZIF-8 and may offer clues to reduce the latent harm of adverse environmental factors to pregnancy.
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Affiliation(s)
- Yu Jiang
- School of Public Health, Chongqing Medical University, Chongqing, China; Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, China
| | - Yanqing Geng
- Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, China
| | - Rufei Gao
- School of Public Health, Chongqing Medical University, Chongqing, China; Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, China
| | - Zhuxiu Chen
- School of Public Health, Chongqing Medical University, Chongqing, China; Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, China
| | - Jun Chen
- College of Pharmacy, Chongqing Medical University, Chongqing, China
| | - Xinyi Mu
- Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, China
| | - Yan Zhang
- School of Public Health, Chongqing Medical University, Chongqing, China; Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, China
| | - Xin Yin
- School of Public Health, Chongqing Medical University, Chongqing, China; Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, China
| | - Xuemei Chen
- School of Public Health, Chongqing Medical University, Chongqing, China; Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, China
| | - Fangfang Li
- School of Public Health, Chongqing Medical University, Chongqing, China; Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, China
| | - Junlin He
- School of Public Health, Chongqing Medical University, Chongqing, China; Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, China.
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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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Liu H, Xu Y, Sun Y, Wu H, Hou J. Tissue-specific toxic effects of nano-copper on zebrafish. ENVIRONMENTAL RESEARCH 2024; 242:117717. [PMID: 37993046 DOI: 10.1016/j.envres.2023.117717] [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: 06/05/2023] [Revised: 09/23/2023] [Accepted: 11/15/2023] [Indexed: 11/24/2023]
Abstract
Understanding the behavior and potential toxicity of copper nanoparticles (nano-Cu) in the aquatic environment is a primary way to assess their environmental risks. In this study, RNA-seq was performed on three different tissues (gills, intestines, and muscles) of zebrafish exposed to nano-Cu, to explore the potential toxic mechanism of nano-Cu on zebrafish. The results indicated that the toxic mechanism of nano-Cu on zebrafish was tissue-specific. Nano-Cu enables the CB1 receptor of the presynaptic membrane of gill cells to affect short-term synaptic plasticity or long-term synaptic changes (ECB-LTD) through DSI and DSE, causing dysfunction of intercellular signal transmission. Imbalance of de novo synthesis of UMP in intestinal cells and its transformation to UDP, UTP, uridine, and uracil, resulted in many functions involved in the pyrimidine metabolic pathway being blocked. Meanwhile, the toxicity of nano-Cu caused abnormal expression of RAD51 gene in muscle cells, which affects the repair of damaged DNA through Fanconi anemia and homologous recombination pathway, thus causing cell cycle disorder. These results provide insights for us to better understand the differences in toxicity of nano-Cu on zebrafish tissues and are helpful for a comprehensive assessment of nano-Cu's effects on aquatic organisms.
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Affiliation(s)
- Haiqiang Liu
- MOE Key Laboratory of Resources and Environmental Systems Optimization, College of Environmental Science and Engineering, North China Electric Power University, Beijing, 102206, China; College of Life and Environmental Sciences, Minzu University of China, Beijing 100081, China; Key Laboratory of Mass Spectrometry Imaging and Metabolomics (State Ethnic Affairs Commission), Centre for Imaging & Systems Biology, Minzu University of China, Beijing, 100081, China
| | - Yanli Xu
- MOE Key Laboratory of Resources and Environmental Systems Optimization, College of Environmental Science and Engineering, North China Electric Power University, Beijing, 102206, China
| | - Yuqiong Sun
- MOE Key Laboratory of Resources and Environmental Systems Optimization, College of Environmental Science and Engineering, North China Electric Power University, Beijing, 102206, China
| | - Haodi Wu
- MOE Key Laboratory of Resources and Environmental Systems Optimization, College of Environmental Science and Engineering, North China Electric Power University, Beijing, 102206, China
| | - Jing Hou
- MOE Key Laboratory of Resources and Environmental Systems Optimization, College of Environmental Science and Engineering, North China Electric Power University, Beijing, 102206, China.
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Kolya H, Kang CW. Toxicity of Metal Oxides, Dyes, and Dissolved Organic Matter in Water: Implications for the Environment and Human Health. TOXICS 2024; 12:111. [PMID: 38393206 PMCID: PMC10892313 DOI: 10.3390/toxics12020111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Revised: 01/23/2024] [Accepted: 01/25/2024] [Indexed: 02/25/2024]
Abstract
This study delves into the critical issue of water pollution caused by the presence of metal oxides, synthetic dyes, and dissolved organic matter, shedding light on their potential ramifications for both the environment and human health. Metal oxides, ubiquitous in industrial processes and consumer products, are known to leach into water bodies, posing a significant threat to aquatic ecosystems. Additionally, synthetic dyes, extensively used in various industries, can persist in water systems and exhibit complex chemical behavior. This review provides a comprehensive examination of the toxicity associated with metal oxides, synthetic dyes, and dissolved organic matter in water systems. We delve into the sources and environmental fate of these contaminants, highlighting their prevalence in natural water bodies and wastewater effluents. The study highlights the multifaceted impacts of them on human health and aquatic ecosystems, encompassing effects on microbial communities, aquatic flora and fauna, and the overall ecological balance. The novelty of this review lies in its unique presentation, focusing on the toxicity of metal oxides, dyes, and dissolved organic matter. This approach aims to facilitate the accessibility of results for readers, providing a streamlined and clear understanding of the reported findings.
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Affiliation(s)
| | - Chun-Won Kang
- Department of Housing Environmental Design, Research Institute of Human Ecology, College of Human Ecology, Jeonbuk National University, Jeonju 54896, Jeonbuk, Republic of Korea;
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Zhuo LB, Liu YM, Jiang Y, Yan Z. Zinc oxide nanoparticles induce acute lung injury via oxidative stress-mediated mitochondrial damage and NLRP3 inflammasome activation: In vitro and in vivo studies. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2024; 341:122950. [PMID: 37979646 DOI: 10.1016/j.envpol.2023.122950] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Revised: 11/02/2023] [Accepted: 11/13/2023] [Indexed: 11/20/2023]
Abstract
The widespread application of zinc oxide nanoparticles (ZnO-NPs) brings convenience to our lives while also renders threats to public health and ecological environment. The lung has been recognized as a primary target of ZnO-NPs, however, the detrimental effects and mechanism of ZnO-NPs on the respiratory system have not been thoroughly characterized so far. To investigate the effect of ZnO-NPs on acute lung injury (ALI), Sprague Dawley rats were intratracheally instilled with ZnO-NPs suspension at doses of 1, 2, and 4 mg/kg/day for 3 consecutive days. Our study revealed that ZnO-NPs induced ALI in rats characterized by increased airway resistance, excessive inflammatory response and lung histological damage. In addition, we identified several molecular biomarkers related to the potential mechanism of ZnO-NP-induced ALI, including oxidative stress, mitochondrial damage, and NLRP3 inflammasome activation. The results of in vitro experiments showed that the viability of A549 cells decreased with the increase in ZnO-NPs concentration. Meanwhile, it was also found that ZnO-NP treatment induced the production of ROS, the decrease in mitochondrial membrane potential and activation of NLRP3 inflammasome in A549 cells. Furthermore, to explore the underlying molecular mechanisms of ZnO-NP-induced ALI, N-acetyl-L-cysteine (a ROS scavenger), Cyclosporin A (an inhibitor for mitochondrial depolarization) and Glibenclamide (an inhibitor for NLRP3 inflammasome activity) were used to pre-treat A549 cells before ZnO-NPs stimulation in the in vitro experiments, respectively. The results from this study suggested that ZnO-NP-induced ROS production triggered the accumulation of damaged mitochondria and assembly of NLRP3 inflammatory complex, leading to maturation and release of IL-1β. Moreover, ZnO-NP-induced NLRP3 inflammasome activation was partly mediated by mitochondrial damage. Taken together, our study suggested that ZnO-NPs induced ALI through oxidative stress-mediated mitochondrial damage and NLRP3 inflammasome activation and provided insight into the mechanisms of ZnO-NPs-induced ALI.
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Affiliation(s)
- Lai-Bao Zhuo
- Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Yu-Mei Liu
- International School of Public Health and One Health, Hainan Medical University, Haikou, China
| | - Yuhan Jiang
- Department of Built Environment, North Carolina A&T State University, Greensboro, NC, 27411, United States
| | - Zhen Yan
- International School of Public Health and One Health, Hainan Medical University, Haikou, China; School of Public Health, Zhengzhou University, Zhengzhou, China.
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23
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Wang Z, Wang M, Zeng X, Yue X, Wei P. Nanomaterial-induced pyroptosis: a cell type-specific perspective. Front Cell Dev Biol 2024; 11:1322305. [PMID: 38264354 PMCID: PMC10803419 DOI: 10.3389/fcell.2023.1322305] [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: 10/17/2023] [Accepted: 12/28/2023] [Indexed: 01/25/2024] Open
Abstract
This review presents the advancements in nanomaterial (NM)-induced pyroptosis in specific types of cells. We elucidate the relevance of pyroptosis and delineate its mechanisms and classifications. We also retrospectively analyze pyroptosis induced by various NMs in a broad spectrum of non-tumorous cellular environments to highlight the multifunctionality of NMs in modulating cell death pathways. We identify key knowledge gaps in current research and propose potential areas for future exploration. This review emphasizes the need to focus on less-studied areas, including the pathways and mechanisms of NM-triggered pyroptosis in non-tumor-specific cell types, the interplay between biological and environmental factors, and the interactions between NMs and cells. This review aims to encourage further investigations into the complex interplay between NMs and pyroptosis, thereby providing a basis for developing safer and more effective nanomedical therapeutic applications.
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Affiliation(s)
- Zhiyong Wang
- Department of Immunology, Zhuhai Campus of Zunyi Medical University, Zhuhai, China
| | - Min Wang
- Department of Pharmaceutics, Zhuhai Campus of Zunyi Medical University, Zhuhai, China
| | - Xuan Zeng
- Department of Pharmaceutics, Guangdong Provincial People’s Hospital Zhuhai Hospital, Zhuhai, China
| | - Xupeng Yue
- College of Bioengineering, Zhuhai Campus of Zunyi Medical University, Zhuhai, China
| | - Pei Wei
- Department of Immunology, Zhuhai Campus of Zunyi Medical University, Zhuhai, China
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24
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Jafar Sameri1 M, Savari F, Mard SA, Rezaie A, Kalantar M. Zinc Oxide Nanoparticles Ameliorate Histological Alterations Through Apoptotic Gene Regulation in Rat Model of Liver Ischemia-Reperfusion Injury. Rep Biochem Mol Biol 2024; 12:619-630. [PMID: 39086591 PMCID: PMC11288243 DOI: 10.61186/rbmb.12.4.619] [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: 02/16/2024] [Accepted: 05/19/2024] [Indexed: 08/02/2024]
Abstract
Background Organ ischemia-reperfusion (IR) is a common clinical condition associated with various situations such as trauma surgery, organ transplantation, and myocardial ischemia. Current therapeutic methods for IR injury have limitations, and nanotechnology, particularly zinc oxide nanoparticles (ZnO NPs), offers new approaches for disease diagnosis and treatment. In this study, we investigated the protective and anti-apoptotic effects of ZnO NPs in liver ischemia-reperfusion (IR) injury in rats. Methods Forty-eight male rats were divided into six groups: sham, ZnO5, ZnO10, ischemia-reperfusion (IR), IR+ZnO5, and IR+ZnO10. The protective effect of ZnO NPs was evaluated by liver enzymes (AST, ALT, Bilirubin, ALP), biochemical (TAC, TNF-α, and MDA), molecular examinations (Bcl2, BAX), and histopathological evaluations (H&E, TUNEL). Results Pre-treatment with ZnO5 and ZnO10 improved hepatic function in IR liver injury, attenuated the levels of oxidants (P = 0.03) and inflammatory mediators, and reduced apoptosis (P = 0). ZnO10 was found to have a greater effect on ischemic reperfusion injury than ZnO5 did. Histopathological examination also showed a dose-dependent decrease in alterations in the IR+ZnO5 and IR+ZnO10 groups. Conclusion Administration of ZnO5 and ZnO10 improved liver function after IR. The findings of this study suggest that ZnO NPs have a protective effect against oxidative stress and apoptosis in liver ischemia-reperfusion injury in rats. These results may have important implications for developing advanced methods in ischemia-reperfusion treatment.
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Affiliation(s)
- Maryam Jafar Sameri1
- Department of physiology, medicine faculty, Abadan University of Medical Sciences, Abadan, Iran.
| | - Feryal Savari
- Department of Medical Basic Sciences, Shoushtar Faculty of Medical Sciences, Shoushtar, Iran.
| | - Seyyed Ali Mard
- Clinical Sciences Research Institute, Alimentary Tract Research Center, Department of Physiology, The School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
| | - Anahita Rezaie
- Department of Pathobiology, School of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran.
| | - Mojtaba Kalantar
- Department of Occupational Health, Shoushtar Faculty of Medical Sciences, Shoushtar, Iran.
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25
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Shaldam MA, Khalil AF, Almahli H, Jaballah MY, Angeli A, Khaleel EF, Badi RM, Elkaeed EB, Supuran CT, Eldehna WM, Tawfik HO. Identification of 3-(5-cyano-6-oxo-pyridin-2-yl)benzenesulfonamides as novel anticancer agents endowed with EGFR inhibitory activity. Arch Pharm (Weinheim) 2024; 357:e2300449. [PMID: 37828544 DOI: 10.1002/ardp.202300449] [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: 08/18/2023] [Revised: 09/24/2023] [Accepted: 09/26/2023] [Indexed: 10/14/2023]
Abstract
New 5-cyano-6-oxo-pyridine-based sulfonamides (6a-m and 8a-d) were designed and synthesized to potentially inhibit both the epidermal growth factor receptor (EGFR) and carbonic anhydrase (CA), with anticancer properties. First, the in vitro anticancer activity of each target substance was tested using Henrietta Lacks cancer cell line and M.D. anderson metastasis breast cancer cell line cells. Then, the possible CA inhibition against the human CA isoforms I, II, and IX was investigated, together with the EGFR inhibitory activity, with the most powerful derivatives. The neighboring methoxy group may have had a steric effect on the target sulfonamides, which prevented them from effectively inhibiting the CA isoforms while effectively inhibiting the EGFR. The effects of the 5-cyanopyridine derivatives 6e and 6l on cell-cycle disruption and the apoptotic potential were then investigated. To investigate the binding mechanism and stability of the target molecules, thorough molecular modeling assessments, including docking and dynamic simulation, were performed.
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Affiliation(s)
- Moataz A Shaldam
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt
| | - Ahmed F Khalil
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Tanta University, Tanta, Egypt
| | - Hadia Almahli
- Department of Chemistry, University of Cambridge, Cambridge, UK
| | - Maiy Y Jaballah
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, Cairo, Abbassia, Egypt
| | - Andrea Angeli
- Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Sesto Fiorentino, Firenze, Italy
| | - Eman F Khaleel
- Department of Medical Physiology, College of Medicine, King Khalid University, Abha, Saudi Arabia
| | - Rehab Mustafa Badi
- Department of Medical Physiology, College of Medicine, King Khalid University, Abha, Saudi Arabia
| | - Eslam B Elkaeed
- Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Riyadh, Saudi Arabia
- Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, Egypt
| | - Claudiu T Supuran
- Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Sesto Fiorentino, Firenze, Italy
| | - Wagdy M Eldehna
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt
- School of Biotechnology, Badr University in Cairo, Badr City, Egypt
| | - Haytham O Tawfik
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Tanta University, Tanta, Egypt
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26
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Pei X, Tang S, Jiang H, Zhang W, Xu G, Zuo Z, Ren Z, Chen C, Shen Y, Li C, Li D. Paeoniflorin recued hepatotoxicity under zinc oxide nanoparticles exposure via regulation on gut-liver axis and reversal of pyroptosis. THE SCIENCE OF THE TOTAL ENVIRONMENT 2023; 904:166885. [PMID: 37678520 DOI: 10.1016/j.scitotenv.2023.166885] [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: 07/01/2023] [Revised: 09/03/2023] [Accepted: 09/04/2023] [Indexed: 09/09/2023]
Abstract
The risks of Zinc oxide nanoparticles (ZnO NPs) applications in biological medicine, food processing industry, agricultural production and the biotoxicity brought by environmental invasion of ZnO NPs both gradually troubled the public due to the lack of research on detoxification strategies. TFEB-regulated autophagy-pyroptosis pathways were found as the crux of the hepatotoxicity induced by ZnO NPs in our latest study. Here, our study served as a connecting link between preceding toxic target and the following protection mechanism of Paeoniflorin (PF). According to a combined analysis of network pharmacology/molecular docking-intestinal microbiota-metabolomics first developed in our study, PF alleviated the hepatotoxicity of ZnO NPs from multiple aspects. The hepatic inflammatory injury and hepatocyte pyroptosis in mice liver exposed to ZnO NPs was significantly inhibited by PF. And the intestinal microbiota disorder and liver metabolic disturbance were rescued. The targets predicted by bioinformatics and the signal trend in subacute toxicological model exhibited the protectiveness of PF related to the SIRT1-mTOR-TFEB pathway. These evidences clarified multiple protective mechanisms of PF which provided a novel detoxification approach against ZnO NPs, and further provided a strategy for the medicinal value development of PF.
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Affiliation(s)
- Xingyao Pei
- Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Jinjing Road No.22, Xiqing District, Tianjin 300392, China; Department of Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Yuanmingyuan West Road No.2, Haidian District, Beijing 100193, China
| | - Shusheng Tang
- Department of Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Yuanmingyuan West Road No.2, Haidian District, Beijing 100193, China
| | - Haiyang Jiang
- Department of Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Yuanmingyuan West Road No.2, Haidian District, Beijing 100193, China
| | - Wenjuan Zhang
- Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Jinjing Road No.22, Xiqing District, Tianjin 300392, China
| | - Gang Xu
- Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Jinjing Road No.22, Xiqing District, Tianjin 300392, China
| | - Zonghui Zuo
- Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Jinjing Road No.22, Xiqing District, Tianjin 300392, China
| | - Zhenhui Ren
- Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Jinjing Road No.22, Xiqing District, Tianjin 300392, China
| | - Chun Chen
- Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Jinjing Road No.22, Xiqing District, Tianjin 300392, China
| | - Yao Shen
- Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Jinjing Road No.22, Xiqing District, Tianjin 300392, China
| | - Cun Li
- Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Jinjing Road No.22, Xiqing District, Tianjin 300392, China
| | - Daowen Li
- Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Jinjing Road No.22, Xiqing District, Tianjin 300392, China; State Key Laboratory of Medicinal Chemical Biology and Tianjin Key Laboratory of Molecular Drug Research, College of Pharmacy, Nankai University, Haihe Education Park, Tongyan Road No.38, Tianjin 300353, China; Tianjin Key Laboratory of Biological Feed Additive Enterprise, S&E Burgeoning Biotechnology (Tianjin) Co., Ltd, Tianjin 300383, China.
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27
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Chen T, Zhang L, Yao L, Luan J, Zhou X, Cong R, Guo X, Qin C, Song N. Zinc oxide nanoparticles-induced testis damage at single-cell resolution: Depletion of spermatogonia reservoir and disorder of Sertoli cell homeostasis. ENVIRONMENT INTERNATIONAL 2023; 181:108292. [PMID: 37918063 DOI: 10.1016/j.envint.2023.108292] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 10/23/2023] [Accepted: 10/25/2023] [Indexed: 11/04/2023]
Abstract
The widespread application of zinc oxide nanoparticles (ZnO NPs) in our daily life has initiated an enhanced awareness of their biosafety concern. An incredible boom of evidence of organismal disorder has accumulated for ZnO NPs, yet there has been no relevant study at the single-cell level. Here, we profiled > 28,000 single-cell transcriptomes and assayed > 25,000 genes in testicular tissues from two healthy Sprague Dawley (SD) rats and two SD rats orally exposed to ZnO NPs. We identified 10 cell types in the rat testis. ZnO NPs had more deleterious effects on spermatogonia, Sertoli cells, and macrophages than on the other cell types. Cell-cell communication analysis indicated a sharp decrease of interaction intensity for all cell types except macrophages in the ZnO NPs group than in the control group. Interestingly, two distinct maturation states of spermatogonia were detected during pseudotime analysis, and ZnO NPs induced reservoir exhaustion of undifferentiated spermatogonia. Mechanically, ZnO NPs triggered fatty acid accumulation in GC-1 cells through protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling and peroxisome proliferator-activated receptor alpha (PPARα)/acyl-CoA oxidase 1 (Acox1) axis, contributing to cell apoptosis. In terms of Sertoli cells, downregulated genes were highly enriched for tight junction. In vitro and in vivo experiments verified that ZnO NPs disrupted blood-testis barrier formation and growth factors synthesis, which subsequently inhibited the proliferation and induced the apoptosis of spermatogonia. As for the macrophages, ZnO NPs activated oxidative stress of Raw264.7 cells through nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway and promoted cell apoptosis through extracellular signal-regulated kinase (ERK) 1/2 pathway. Collectively, our work reveals the cell type-specific and cellularly heterogenetic mechanism of ZnO NPs-induced testis damage and paves the path for identifying putative biomarkers and therapeutics against this disorder.
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Affiliation(s)
- Tong Chen
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 210000 Nanjing, PR China
| | - Lin Zhang
- Clinical Medical Research Center for Women and Children Diseases, Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, 250001 Jinan, PR China; Key Laboratory of Birth Defect Prevention and Genetic Medicine of Shandong Health Commission, Shandong University, 250001 Jinan, PR China
| | - Liangyu Yao
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 210000 Nanjing, PR China
| | - Jiaochen Luan
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 210000 Nanjing, PR China
| | - Xiang Zhou
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 210000 Nanjing, PR China
| | - Rong Cong
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 210000 Nanjing, PR China
| | - Xuejiang Guo
- State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
| | - Chao Qin
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 210000 Nanjing, PR China.
| | - Ninghong Song
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 210000 Nanjing, PR China.
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Li J, Huang Q, Lv M, Ma W, Sun J, Zhong X, Hu R, Ma M, Han Z, Zhang W, Feng W, Sun X, Zhou X. Role of liensinine in sensitivity of activated macrophages to ferroptosis and in acute liver injury. Cell Death Discov 2023; 9:189. [PMID: 37353487 DOI: 10.1038/s41420-023-01481-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 05/14/2023] [Accepted: 06/12/2023] [Indexed: 06/25/2023] Open
Abstract
Acute liver injury (ALI) is an acute inflammatory liver disease with a high mortality rate. Alternatively, activated macrophages (AAMs) have been linked to the inflammation and recovery of ALI. However, the mechanism underlying AAM death in ALI has not been studied sufficiently. We used liensinine (Lie) as a drug of choice after screening a library of small-molecule monomers with 1488 compounds from traditional Chinese remedies. In ALI, we evaluated the potential therapeutic effects and underlying mechanisms of action of the drug in ALI and found that it effectively inhibited RSL3-induced ferroptosis in AAM. Lie significantly reduced lipid peroxidation in RSL3-generated AAM. It also improved the survival rate of LPS/D-GalN-treated mice, reduced serum transaminase activity, suppressed inflammatory factor production, and may have lowered AAM ferroptosis in ALI. Lie also inhibited ferritinophagy and blocked Fe2+ synthesis. Following combined treatment with RSL3 and Lie, super-resolution microscopy revealed a close correlation between ferritin and LC3-positive vesicles in the AAM. The co-localization of ferritin and LC3 with LAMP1 was significantly reduced. These findings suggest that Lie may ameliorate ALI by inhibiting ferritinophagy and enhancing AMM resistance to ferroptosis by inhibiting autophagosome-lysosome fusion. Therefore, Lie may be used as a potential therapeutic agent for patients with ALI.
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Affiliation(s)
- Jing Li
- Department of Liver Disease, The Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, China
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, China
- Macau University of Science and Technology, Faculty of Chinese Medicine, Taipa, Macao, 999078, China
| | - Qi Huang
- Department of Liver Disease, The Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, China
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, China
| | - Minling Lv
- Department of Liver Disease, The Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, China
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, China
| | - Wenfeng Ma
- Department of Liver Disease, The Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, China
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, China
| | - Jialing Sun
- Department of Liver Disease, The Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, China
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, China
| | - Xin Zhong
- Department of Liver Disease, The Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, China
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, China
| | - Rui Hu
- Department of Liver Disease, The Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, China
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, China
| | - MengQing Ma
- Department of Liver Disease, The Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, China
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, China
| | - Zhiyi Han
- Department of Liver Disease, The Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, China
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, China
| | - Wei Zhang
- Department of Liver Disease, The Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, China
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, China
| | - Wenxing Feng
- Department of Liver Disease, The Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, China
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, China
| | - Xinfeng Sun
- Department of Liver Disease, The Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, China
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, China
| | - Xiaozhou Zhou
- Department of Liver Disease, The Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518033, China.
- Department of Liver Disease, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, China.
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29
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Banaee M, Sagvand S, Sureda A, Amini M, Haghi BN, Sopjani M, Faggio C. Evaluation of single and combined effects of mancozeb and metalaxyl on the transcriptional and biochemical response of zebrafish (Danio rerio). Comp Biochem Physiol C Toxicol Pharmacol 2023; 268:109597. [PMID: 36889533 DOI: 10.1016/j.cbpc.2023.109597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 02/23/2023] [Accepted: 03/01/2023] [Indexed: 03/08/2023]
Abstract
Mancozeb and metalaxyl are fungicidal agents frequently used in combination to control fungi in crops that may affect non-target organisms when entering ecosystems. This study aims to evaluate the environmental effects of Mancozeb (MAN) and Metalaxyl (MET), alone and in combination, on zebrafish (Danio rerio) as an experimental model. The oxidative stress biomarkers and the transcription of genes involved in detoxification in zebrafish (Danio rerio) were assessed after co-exposure to MAN (0, 5.5, and 11 μg L-1) and MET (0, 6.5, and 13 mg L-1) for 21 days. Exposure to MAN and MET induced a significant increase in the expression of genes related to detoxification mechanisms (Ces2, Cyp1a, and Mt2). Although Mt1 gene expression increased in fish exposed to 11 μg L-1 of MAN combined with 13 mg L-1 of MET, Mt1 expression was down-regulated significantly in other experimental groups (p < 0.05). The combined exposure to both fungicides showed synergistic effects in the expression levels that are manifested mainly at the highest concentration. Although a significant (p < 0.05) increase in alkaline phosphatase (ALP) and transaminases (AST and ALT), catalase activities, the total antioxidant capacity, and malondialdehyde (MDA) contents in the hepatocytes of fish exposed to MAN and MET alone and in combination was detected, lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT) activities, and hepatic glycogen content decreased significantly (p < 0.05). Overall, these results emphasize that combined exposure to MET and MAN can synergistically affect the transcription of genes involved in detoxification (except Mt1 and Mt2) and biochemical indicators in zebrafish.
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Affiliation(s)
- Mahdi Banaee
- Aquaculture Department, Faculty of Natural Resources and the Environment, Behbahan Khatam Alanbia University of Technology, Behbahan, Iran.
| | - Shiva Sagvand
- Aquaculture Department, Faculty of Natural Resources and the Environment, Behbahan Khatam Alanbia University of Technology, Behbahan, Iran
| | - Antoni Sureda
- Research Group on Community Nutrition and Oxidative Stress, Health Research Institute of the Balearic Islands (IdISBa), and CIBEROBN Fisiopatología de la Obesidad la Nutrición, University of Balearic Islands, 07122 Palma de Mallorca, Spain.
| | - Mohammad Amini
- Aquaculture Department, Faculty of Natural Resources and the Environment, Behbahan Khatam Alanbia University of Technology, Behbahan, Iran
| | - Behzad Nematdoost Haghi
- Aquaculture Department, Faculty of Natural Resources and the Environment, Behbahan Khatam Alanbia University of Technology, Behbahan, Iran
| | - Mentor Sopjani
- Faculty of Medicine of the University of Prishtina, Prishtina, Kosovo.
| | - Caterina Faggio
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
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30
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Tkachenko A, Onishchenko A, Myasoedov V, Yefimova S, Havranek O. Assessing regulated cell death modalities as an efficient tool for in vitro nanotoxicity screening: a review. Nanotoxicology 2023; 17:218-248. [PMID: 37083543 DOI: 10.1080/17435390.2023.2203239] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/22/2023]
Abstract
Nanomedicine is a fast-growing field of nanotechnology. One of the major obstacles for a wider use of nanomaterials for medical application is the lack of standardized toxicity screening protocols for assessing the safety of newly synthesized nanomaterials. In this review, we focus on less frequently studied nanomaterials-induced regulated cell death (RCD) modalities, including eryptosis, necroptosis, pyroptosis, and ferroptosis, as a tool for in vitro nanomaterials safety evaluation. We summarize the latest insights into the mechanisms that mediate these RCDs in response to nanomaterials exposure. Comprehensive data from reviewed studies suggest that ROS (reactive oxygen species) overproduction and ROS-mediated pathways play a central role in nanomaterials-induced RCDs activation. On the other hand, studies also suggest that individual properties of nanomaterials, including size, shape, or surface charge, could determine specific toxicity pathways with consequent RCD induction as well. We anticipate that the evaluation of RCDs can become one of the mechanism-based screening methods in nanotoxicology. In addition to the toxicity assessment, evaluation of necroptosis-, pyroptosis-, and ferroptosis-promoting capacity of nanomaterials could simultaneously provide useful information for specific medical applications as could be their anti-tumor potential. Moreover, a detailed understanding of molecular mechanisms driving nanomaterials-mediated induction of immunogenic RCDs will substantially aid novel anti-tumor nanodrugs development.
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Affiliation(s)
- Anton Tkachenko
- BIOCEV, First Faculty of Medicine, Charles University, Vestec, Czechia
- Research Institute of Experimental and Clinical Medicine, Kharkiv National Medical University, Kharkiv, Ukraine
| | - Anatolii Onishchenko
- Research Institute of Experimental and Clinical Medicine, Kharkiv National Medical University, Kharkiv, Ukraine
| | - Valeriy Myasoedov
- Department of Medical Biology, Kharkiv National Medical University, Kharkiv, Ukraine
| | - Svetlana Yefimova
- Institute for Scintillation Materials, National Academy of Sciences of Ukraine, Kharkiv, Ukraine
| | - Ondrej Havranek
- BIOCEV, First Faculty of Medicine, Charles University, Vestec, Czechia
- Department of Hematology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czechia
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Carnide G, Champouret Y, Valappil D, Vahlas C, Mingotaud A, Clergereaux R, Kahn ML. Secured Nanosynthesis-Deposition Aerosol Process for Composite Thin Films Incorporating Highly Dispersed Nanoparticles. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2023; 10:e2204929. [PMID: 36529954 PMCID: PMC9929256 DOI: 10.1002/advs.202204929] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Revised: 11/28/2022] [Indexed: 06/17/2023]
Abstract
Application of nanocomposites in daily life requires not only small nanoparticles (NPs) well dispersed in a matrix, but also a manufacturing process that is mindful of the operator and the environment. Avoiding any exposure to NPs is one such way, and direct liquid reaction-injection (DLRI) aims to fulfill this need. DLRI is based on the controlled in situ synthesis of NPs from the decomposition of suitable organometallic precursors in conditions that are compatible with a pulsed injection mode of an aerosol into a downstream process. Coupled with low-pressure plasma, DLRI produces nanocomposite with homogeneously well-dispersed small nanoparticles that in the particular case of ZnO-DLC nanocomposite exhibit unique properties. DLRI favorably compares with the direct liquid injection of ex situ formed NPs. The exothermic hydrolysis reaction of the organometallic precursor at the droplet-gas interface leads to the injection of small and highly dispersed NPs and, consequently, the deposition of fine and controlled distribution in the nanocomposite. The scope of DLRI nanosynthesis has been extended to several metal oxides such as zinc, tin, tungsten, and copper to generalize the concept. Hence, DLRI is an attractive method to synthesize, inject, and deposit nanoparticles and meets the prevention and atom economy requirements of green chemistry.
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Affiliation(s)
- Guillaume Carnide
- LCCCNRS UPR8241Université de Toulouse205 route de NarbonneToulouse31077France
- LAPLACECNRS UMR5213Université de Toulouse118 route de NarbonneToulouse31062France
| | - Yohan Champouret
- LCCCNRS UPR8241Université de Toulouse205 route de NarbonneToulouse31077France
- LAPLACECNRS UMR5213Université de Toulouse118 route de NarbonneToulouse31062France
| | - Divyendu Valappil
- Laboratoire des IMRCPUniversité de ToulouseCNRS UMR 5623, Université Toulouse III – Paul Sabatier, 118 route de NarbonneToulouse31062France
| | - Constantin Vahlas
- CIRIMATCNRS UMR5085Université de Toulouse4 allée Émile Monso, BP‐44362, Toulouse Cedex 4Toulouse31030France
| | - Anne‐Françoise Mingotaud
- Laboratoire des IMRCPUniversité de ToulouseCNRS UMR 5623, Université Toulouse III – Paul Sabatier, 118 route de NarbonneToulouse31062France
| | - Richard Clergereaux
- LAPLACECNRS UMR5213Université de Toulouse118 route de NarbonneToulouse31062France
| | - Myrtil L. Kahn
- LCCCNRS UPR8241Université de Toulouse205 route de NarbonneToulouse31077France
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Luo X, Xie D, Su J, Hu J. Inflammatory Genes Associated with Pristine Multi-Walled Carbon Nanotubes-Induced Toxicity in Ocular Cells. Int J Nanomedicine 2023; 18:2465-2484. [PMID: 37192896 PMCID: PMC10183194 DOI: 10.2147/ijn.s394694] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 05/06/2023] [Indexed: 05/18/2023] Open
Abstract
Background The wide application of multi-walled carbon nanotubes (MWCNTs) in various fields has raised enormous concerns regarding their safety for humans. However, studies on the toxicity of MWCNTs to the eye are rare and potential molecular mechanisms are completely lacking. This study was to evaluate the adverse effects and toxic mechanisms of MWCNTs on human ocular cells. Methods Human retinal pigment epithelial cells (ARPE-19) were treated with pristine MWCNTs (7-11 nm) (0, 25, 50, 100 or 200 μg/mL) for 24 hours. MWCNTs uptake into ARPE-19 cells was examined using transmission electron microscopy (TEM). The cytotoxicity was evaluated by CCK-8 assay. The death cells were detected by Annexin V-FITC/PI assay. RNA profiles in MWCNT-exposed and non-exposed cells (n = 3) were analyzed using RNA-sequencing. The differentially expressed genes (DEGs) were identified through the DESeq2 method and hub of which were filtered by weighted gene co-expression, protein-protein interaction (PPI) and lncRNA-mRNA co-expression network analyses. The mRNA and protein expression levels of crucial genes were verified using quantitative polymerase chain reaction (qPCR), colorimetric analysis, ELISA and Western blotting. The toxicity and mechanisms of MWCNTs were also validated in human corneal epithelial cells (HCE-T). Results TEM analysis indicated the internalization of MWCNTs into ARPE-19 cells to cause cell damage. Compared with untreated ARPE-19 cells, those exposed to MWCNTs exhibited significantly decreased cell viabilities in a dose-dependent manner. The percentages of apoptotic (early, Annexin V positive; late, Annexin V and PI positive) and necrotic (PI positive) cells were significantly increased after exposure to IC50 concentration (100 μg/mL). A total of 703 genes were identified as DEGs; 254 and 56 of them were, respectively, included in darkorange2 and brown1 modules that were significantly associated with MWCNT exposure. Inflammation-related genes (including CXCL8, MMP1, CASP3, FOS, CXCL2 and IL11) were screened as hub genes by calculating the topological characteristics of genes in the PPI network. Two dysregulated long non-coding RNAs (LUCAT1 and SCAT8) were shown to regulate these inflammation-related genes in the co-expression network. The mRNA levels of all eight genes were confirmed to be upregulated, while caspase-3 activity and the release of CXCL8, MMP1, CXCL2, IL11 and FOS proteins were demonstrated to be increased in MWCNT-treated ARPE-19 cells. MWCNTs exposure also can induce cytotoxicity and increase the caspase-3 activity and the expression of LUCAT1, MMP1, CXCL2, and IL11 mRNA and protein in HCE-T cells. Conclusion Our study provides promising biomarkers for monitoring MWCNT-induced eye disorders and targets for developing preventive and therapeutic strategies.
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Affiliation(s)
- Xiaogang Luo
- College of Textile and Clothing Engineering, Soochow University, Suzhou, 215123, People’s Republic of China
- Correspondence: Xiaogang Luo; Jianchen Hu, Tel +86-0512-67162531, Email ;
| | - Dongli Xie
- College of Textile and Clothing Engineering, Soochow University, Suzhou, 215123, People’s Republic of China
| | - Jing Su
- Shanghai Institute of Spacecraft Equipment, Shanghai, 200240, People’s Republic of China
| | - Jianchen Hu
- College of Textile and Clothing Engineering, Soochow University, Suzhou, 215123, People’s Republic of China
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