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Syed S, Nissilä E, Ruhanen H, Fudo S, Gaytán MO, Sihvo SP, Lorey MB, Metso J, Öörni K, King SJ, Oommen OP, Jauhiainen M, Meri S, Käkelä R, Haapasalo K. Streptococcus pneumoniae pneumolysin and neuraminidase A convert high-density lipoproteins into pro-atherogenic particles. iScience 2021; 24:102535. [PMID: 34124613 PMCID: PMC8175417 DOI: 10.1016/j.isci.2021.102535] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 04/19/2021] [Accepted: 05/10/2021] [Indexed: 11/19/2022] Open
Abstract
High-density lipoproteins (HDLs) are a group of different subpopulations of sialylated particles that have an essential role in the reverse cholesterol transport (RCT) pathway. Importantly, changes in the protein and lipid composition of HDLs may lead to the formation of particles with reduced atheroprotective properties. Here, we show that Streptococcus pneumoniae pneumolysin (PLY) and neuraminidase A (NanA) impair HDL function by causing chemical and structural modifications of HDLs. The proteomic, lipidomic, cellular, and biochemical analysis revealed that PLY and NanA induce significant changes in sialic acid, protein, and lipid compositions of HDL. The modified HDL particles have reduced cholesterol acceptor potential from activated macrophages, elevated levels of malondialdehyde adducts, and show significantly increased complement activating capacity. These results suggest that accumulation of these modified HDL particles in the arterial intima may present a trigger for complement activation, inflammatory response, and thereby promote atherogenic disease progression.
S. pneumoniae molecules PLY and NanA target human high-density lipoprotein (HDL). These interactions result in major modifications in the HDL proteome and lipidome. Microbially modified HDL activates humoral and cell-mediated innate immune responses. The activated immune response mediates formation of pro-atherogenic epitopes on HDL.
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Affiliation(s)
- Shahan Syed
- Department of Bacteriology and Immunology, University of Helsinki, 00014 Helsinki, Finland
| | - Eija Nissilä
- Department of Bacteriology and Immunology, University of Helsinki, 00014 Helsinki, Finland
| | - Hanna Ruhanen
- Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, 00014 Helsinki, Finland
- Helsinki University Lipidomics Unit (HiLIPID), Helsinki Institute for Life Science (HiLIFE) and Biocenter Finland, Helsinki 00014, Finland
| | - Satoshi Fudo
- Department of Bacteriology and Immunology, University of Helsinki, 00014 Helsinki, Finland
| | - Meztlli O. Gaytán
- Center for Microbial Pathogenesis, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA
| | - Sanna P. Sihvo
- Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, 00014 Helsinki, Finland
- Helsinki University Lipidomics Unit (HiLIPID), Helsinki Institute for Life Science (HiLIFE) and Biocenter Finland, Helsinki 00014, Finland
| | | | - Jari Metso
- Minerva Foundation Institute for Medical Research, Biomedicum, 00290 Helsinki, Finland
- Genomics and Biomarkers Unit, National Institute for Health and Welfare, Helsinki, Finland
| | | | - Samantha J. King
- Center for Microbial Pathogenesis, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA
- Department of Pediatrics, The Ohio State University, Columbus, OH 43210, USA
| | - Oommen P. Oommen
- Bioengineering and Nanomedicine Lab, Faculty of Medicine and Health Technology and BioMediTech Institute, Tampere University, 33720 Tampere, Finland
| | - Matti Jauhiainen
- Minerva Foundation Institute for Medical Research, Biomedicum, 00290 Helsinki, Finland
- Genomics and Biomarkers Unit, National Institute for Health and Welfare, Helsinki, Finland
| | - Seppo Meri
- Department of Bacteriology and Immunology, University of Helsinki, 00014 Helsinki, Finland
| | - Reijo Käkelä
- Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, 00014 Helsinki, Finland
- Helsinki University Lipidomics Unit (HiLIPID), Helsinki Institute for Life Science (HiLIFE) and Biocenter Finland, Helsinki 00014, Finland
| | - Karita Haapasalo
- Department of Bacteriology and Immunology, University of Helsinki, 00014 Helsinki, Finland
- Corresponding author
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Rosta V, Trentini A, Passaro A, Zuliani G, Sanz JM, Bosi C, Bonaccorsi G, Bellini T, Cervellati C. Sex Difference Impacts on the Relationship between Paraoxonase-1 (PON1) and Type 2 Diabetes. Antioxidants (Basel) 2020; 9:antiox9080683. [PMID: 32751395 PMCID: PMC7463677 DOI: 10.3390/antiox9080683] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 07/27/2020] [Accepted: 07/28/2020] [Indexed: 12/11/2022] Open
Abstract
Type-2 diabetes (T2D) and its cardiovascular complications are related to sex. Increasing evidence suggests that paraoxonase 1 (PON1) activity, an antioxidant enzyme bound to high-density lipoproteins (HDL), is implicated in the onset and clinical progression of T2D. Since we previously showed that PON1 is a sexual dimorphic protein, we now investigated whether sex might impact the relationship between PON1 and this chronic disease. To address this aim, we assessed PON1 activity in the sera of 778 patients, including controls (women, n = 383; men, n = 198) and diabetics (women, n = 79; men = 118). PON1 activity decreased in both women and men with T2D compared with controls (p < 0.05 and p > 0.001, respectively), but the change was 50% larger in the female cohort. In line with this result, the enzyme activity was associated with serum glucose level only in women (r = -0.160, p = 0.002). Notably, only within this gender category, lower PON1 activity was independently associated with increased odds of being diabetic (odds ratio (95% Confidence interval: 2.162 (1.075-5.678)). In conclusion, our study suggests that PON1-deficiency in T2D is a gender-specific phenomenon, with women being more affected than men. This could contribute to the partial loss of female cardiovascular advantage associated with T2D.
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Affiliation(s)
- Valentina Rosta
- Department of Biomedical and Specialist Surgical Sciences, Section of Medical Biochemistry, Molecular Biology and Genetics, University of Ferrara, 44121 Ferrara, Italy; (V.R.); (T.B.)
| | - Alessandro Trentini
- Department of Biomedical and Specialist Surgical Sciences, Section of Medical Biochemistry, Molecular Biology and Genetics, University of Ferrara, 44121 Ferrara, Italy; (V.R.); (T.B.)
- Correspondence: (A.T.); (A.P.); Tel.: +39-532-455322 (A.T.); +39-532-237017 (A.P.)
| | - Angelina Passaro
- Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy; (G.Z.); (J.M.S.); (C.B.); (G.B.); (C.C.)
- Correspondence: (A.T.); (A.P.); Tel.: +39-532-455322 (A.T.); +39-532-237017 (A.P.)
| | - Giovanni Zuliani
- Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy; (G.Z.); (J.M.S.); (C.B.); (G.B.); (C.C.)
| | - Juana Maria Sanz
- Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy; (G.Z.); (J.M.S.); (C.B.); (G.B.); (C.C.)
| | - Cristina Bosi
- Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy; (G.Z.); (J.M.S.); (C.B.); (G.B.); (C.C.)
| | - Gloria Bonaccorsi
- Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy; (G.Z.); (J.M.S.); (C.B.); (G.B.); (C.C.)
- Menopause and Osteoporosis Centre, University of Ferrara, 44124 Ferrara, Italy
- Center of Gender Medicine, University of Ferrara, 44121 Ferrara, Italy
| | - Tiziana Bellini
- Department of Biomedical and Specialist Surgical Sciences, Section of Medical Biochemistry, Molecular Biology and Genetics, University of Ferrara, 44121 Ferrara, Italy; (V.R.); (T.B.)
- Center of Gender Medicine, University of Ferrara, 44121 Ferrara, Italy
| | - Carlo Cervellati
- Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy; (G.Z.); (J.M.S.); (C.B.); (G.B.); (C.C.)
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Kotur-Stevuljević J, Vekić J, Stefanović A, Zeljković A, Ninić A, Ivanišević J, Miljković M, Sopić M, Munjas J, Mihajlović M, Spasić S, Jelić-Ivanović Z, Spasojević-Kalimanovska V. Paraoxonase 1 and atherosclerosis-related diseases. Biofactors 2020; 46:193-205. [PMID: 31400246 DOI: 10.1002/biof.1549] [Citation(s) in RCA: 51] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Accepted: 07/16/2019] [Indexed: 12/16/2022]
Abstract
A direct and an indirect relationship between paraoxonase 1 (PON1) and atherosclerosis exists. Given PON1's physical location within high-density lipoprotein (HDL) particles and its recognized enzyme activity, it is certainly reasonable to suggest that PON1 facilitates the antiatherogenic nature of HDL particles. PON1 also plays a role in regulating reverse cholesterol transport, antioxidative, anti-inflammatory, antiapoptotic, vasodilative, and antithrombotic activities and several endothelial cell functions. HDL dysfunctionality is a more recent issue and seems to be centered on pathological conditions affecting HDL structure and size profiles. This review is focused on the role of PON1 status in different atherosclerosis-related diseases that we have studied over the last twenty years (coronary heart disease, acute ischemic stroke, diabetes mellitus type 2, end-stage renal disease, chronic obstructive pulmonary disease, and sarcoidosis) with the aim to determine the true value of PON1 as a biomarker. The role of PON1 in cancer is also covered, as risk factors and mechanisms underlying both atherosclerosis and cancer share common features.
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Affiliation(s)
- Jelena Kotur-Stevuljević
- Department for Medical Biochemistry, University of Belgrade, Faculty of Pharmacy, Belgrade, Serbia
| | - Jelena Vekić
- Department for Medical Biochemistry, University of Belgrade, Faculty of Pharmacy, Belgrade, Serbia
| | - Aleksandra Stefanović
- Department for Medical Biochemistry, University of Belgrade, Faculty of Pharmacy, Belgrade, Serbia
| | - Aleksandra Zeljković
- Department for Medical Biochemistry, University of Belgrade, Faculty of Pharmacy, Belgrade, Serbia
| | - Ana Ninić
- Department for Medical Biochemistry, University of Belgrade, Faculty of Pharmacy, Belgrade, Serbia
| | - Jasmina Ivanišević
- Department for Medical Biochemistry, University of Belgrade, Faculty of Pharmacy, Belgrade, Serbia
| | - Milica Miljković
- Department for Medical Biochemistry, University of Belgrade, Faculty of Pharmacy, Belgrade, Serbia
| | - Miron Sopić
- Department for Medical Biochemistry, University of Belgrade, Faculty of Pharmacy, Belgrade, Serbia
| | - Jelena Munjas
- Department for Medical Biochemistry, University of Belgrade, Faculty of Pharmacy, Belgrade, Serbia
| | - Marija Mihajlović
- Department for Medical Biochemistry, University of Belgrade, Faculty of Pharmacy, Belgrade, Serbia
| | - Slavica Spasić
- Department for Medical Biochemistry, University of Belgrade, Faculty of Pharmacy, Belgrade, Serbia
| | - Zorana Jelić-Ivanović
- Department for Medical Biochemistry, University of Belgrade, Faculty of Pharmacy, Belgrade, Serbia
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Kang I, Park M, Yang SJ, Lee M. Lipoprotein Lipase Inhibitor, Nordihydroguaiaretic Acid, Aggravates Metabolic Phenotypes and Alters HDL Particle Size in the Western Diet-Fed db/db Mice. Int J Mol Sci 2019; 20:ijms20123057. [PMID: 31234537 PMCID: PMC6627211 DOI: 10.3390/ijms20123057] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2019] [Revised: 06/19/2019] [Accepted: 06/20/2019] [Indexed: 12/19/2022] Open
Abstract
Lipoprotein lipase (LPL) hydrolyzes triglycerides in lipoprotein to supply fatty acids, and its deficiency leads to hypertriglyceridemia, thereby inducing metabolic syndrome (MetSyn). Nordihydroguaiaretic acid (NDGA) has been recently reported to inhibit LPL secretion by endoplasmic reticulum (ER)-Golgi redistribution. However, the role of NDGA on dyslipidemia and MetSyn remains unclear. To address this question, leptin receptor knock out (KO)-db/db mice were randomly assigned to three different groups: A normal AIN76-A diet (CON), a Western diet (WD) and a Western diet with 0.1% NDGA and an LPL inhibitor, (WD+NDGA). All mice were fed for 12 weeks. The LPL inhibition by NDGA was confirmed by measuring the systemic LPL mass and adipose LPL gene expression. We investigated whether the LPL inhibition by NDGA alters the metabolic phenotypes. NDGA led to hyperglycemia, hypertriglyceridemia, and hypercholesterolemia. More strikingly, the supplementation of NDGA increased the percentage of high density lipoprotein (HDL)small (HDL3a+3b+3c) and decreased the percentage of HDLlarge (HDL2a+2b) compared to the WD group, which indicates that LPL inhibition modulates HDL subclasses. was NDGA increased adipose inflammation but had no impact on hepatic stress signals. Taken together, these findings demonstrated that LPL inhibition by NDGA aggravates metabolic parameters and alters HDL particle size.
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Affiliation(s)
- Inhae Kang
- Department of Food Science and Nutrition, Jeju National University, Jeju 63243, Korea.
| | - Miyoung Park
- Research Institute of Obesity Sciences, Sungshin Women's University, Seoul 01133, Korea.
| | - Soo Jin Yang
- Department of Food and Nutrition, Seoul Women's University, Seoul 01797, Korea.
| | - Myoungsook Lee
- Research Institute of Obesity Sciences, Sungshin Women's University, Seoul 01133, Korea.
- Department of Food and Nutrition, Sungshin Women's University, Seoul 01133, Korea.
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Stefanović A, Zeljković A, Vekić J, Spasojević-Kalimanovska V, Jelić-Ivanović Z, Spasić S. Dyslipidemia in type 2 diabetes mellitus. ARHIV ZA FARMACIJU 2019. [DOI: 10.5937/arhfarm1905338s] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
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Distribution of Paraoxonase-1 (PON-1) and Lipoprotein Phospholipase A2 (Lp-PLA2) across Lipoprotein Subclasses in Subjects with Type 2 Diabetes. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2018; 2018:1752940. [PMID: 30524650 PMCID: PMC6247389 DOI: 10.1155/2018/1752940] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Accepted: 10/15/2018] [Indexed: 12/11/2022]
Abstract
Paraoxonase-1 (PON1) and lipoprotein phospholipase A2 (Lp-PLA2) may exert an important protective role by preventing the oxidative transformation of high- and low-density lipoproteins (HDL and LDL, respectively). The activity of both enzymes is influenced by lipidome and proteome of the lipoprotein carriers. T2DM typically presents significant changes in the molecular composition of the lipoprotein subclasses. Thus, it becomes relevant to understand the interaction of PON1 and Lp-PLA2 with the subspecies of HDL, LDL, and other lipoproteins in T2DM. Serum levels of PON1-arylesterase and PON1-lactonase and Lp-PLA2 activities and lipoprotein subclasses were measured in 202 nondiabetic subjects (controls) and 92 T2DM outpatients. Arylesterase, but not lactonase or Lp-PLA2 activities, was inversely associated with TD2M after adjusting for potential confounding factors such as age, sex, smoking, body mass index, hypertension, and lipoprotein subclasses (odds ratio = 3.389, 95% confidence interval 1.069–14.756). Marked difference between controls and T2DM subjects emerged from the analyses of the associations of the three enzyme activities and lipoprotein subclasses. Arylesterase was independently related with large HDL-C and small intermediate-density lipoprotein cholesterol (IDL-C) in controls while, along with lactonase, it was related with small low-density lipoprotein cholesterol LDL-C, all IDL-C subspecies, and very low-density lipoprotein cholesterol (VLDL-C) in T2DM (p < 0.05 for all). Concerning Lp-PLA2, there were significant relationships with small LDL-C, large IDL-C, and VLDL-C only among T2DM subjects. Our study showed that T2DM subjects have lower levels of PON1-arylesterase compared to controls and that T2DM occurrence may coincide with a shift of PON1 and Lp-PLA2 towards the more proatherogenic lipoprotein subclasses. The possibility of a link between the two observed phenomena requires further investigations.
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Wu D, Wu C, Zhong Y. The association between paraoxonase 1 activity and the susceptibilities of diabetes mellitus, diabetic macroangiopathy and diabetic microangiopathy. J Cell Mol Med 2018; 22:4283-4291. [PMID: 29981194 PMCID: PMC6111876 DOI: 10.1111/jcmm.13711] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2018] [Accepted: 05/03/2018] [Indexed: 01/22/2023] Open
Abstract
We carried out this meta-analysis to explore the influence of paraoxonase 1 activity on the susceptibility of diabetes mellitus (DM), diabetic macroangiopathy and diabetic microangiopathy. Relevant studies were identified from PubMed, Web of Science and CNKI without language limitation, following the inclusion and exclusion criteria. Statistical analyses were implemented with the STATA 12.0 statistical software. Thirty-six case-control studies were included in the meta-analyses, in which 35 for the association between paraoxonase 1 activity and DM risk, 8 for diabetic macroangiopathy and 7 for diabetic microangiopathy. Paraoxonase 1 activity was significantly associated with the susceptibility of DM in pooled population (SMD = -1.37, 95% CI = -1.79 ∼ -0.96, P = .000), and Asians (SMD = -2.00, 95% CI = -2.56 ∼ -1.44, P = .000), but not in non-Asians (SMD = -0.44, 95% CI = -0.91 ∼ 0.03, P = .069). However, marked heterogeneity was existed (I2 = 98.10%, P = .000) and subgroup analyses failed to investigate the sources of heterogeneity. Then, meta-regression was performed and found that ethnicity could explain the observed between-study heterogeneity (P = .002). Meanwhile, significant associations were found between paraoxonase 1 activity and diabetic macroangiopathy (SMD = -1.06, 95% CI = -1.63 ∼ -0.48, P = .000) and diabetic microangiopathy (SMD = -0.72, 95% CI = -1.32 ∼ -0.13, P = .018). In conclusion, paraoxonase 1 activity plays important roles in the risk of DM, diabetic macroangiopathy and microangiopathy with ethnicity differences. Further studies with large sample and well design are needed to confirm these results.
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Affiliation(s)
- Diling Wu
- ICU CenterThe Second Xiangya HospitalCentral South UniversityChangshaHunanChina
| | - Chenfang Wu
- ICU CenterThe Second Xiangya HospitalCentral South UniversityChangshaHunanChina
| | - Yanjun Zhong
- ICU CenterThe Second Xiangya HospitalCentral South UniversityChangshaHunanChina
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Karakaya P, Ozdemir B, Mert M, Okuturlar Y. Relation of Paraoxonase 1 Activity with Biochemical Variables, Brachial Artery Intima-Media Thickness in Patients with Diabetes with or without Obesity. Obes Facts 2018; 11:56-66. [PMID: 29439274 PMCID: PMC5869602 DOI: 10.1159/000486513] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2017] [Accepted: 12/21/2017] [Indexed: 01/31/2023] Open
Abstract
AIM The sodium-sparing effect of insulin leads to increase in total sodium pool of the body which is a chronic stimulus for atrial natriuretic peptide (ANP). In our study we aimed to determine the relationship between ANP and microvascular complications of diabetes. METHODS 60 patients, 30-70 years old, with the diagnosis of type 2 diabetes mellitus (DM) are enrolled into the study. Patients with a chronic disease other than DM are excluded. Blood samples for routine biochemical tests are taken after at least 12 h fasting at 8-9 am. Blood samples for glucose and insulin levels are taken 2 h after a standard meal. Blood tubes with EDTA are used for ANP levels. The microvascular complications of the patients are evaluated. RESULTS 32 of the patients had microvascular complications. Age, BMI, waist and hip circumferences, and ANP levels were significantly higher in the group with microvascular complications. There were no significant differences in waist-to-hip ratio, blood glucose, HbA1c, fasting insulin, postprandial insulin, fasting HOMA, postprandial HOMA as well as sodium, potassium, magnesium, calcium and lipid levels between the two groups. When the relationship between ANP and obesity, retinopathy, neuropathy, nephropathy, diabetes time, HbA1c, or sex are evaluated separately, the only significant parameters related to ANP were obesity and retinopathy. CONCLUSION In our study we have found that there was a significant relationship between ANP levels and microvascular complications of diabetes. Future studies are needed to show if ANP is the stimulus of microvascular complication development/progression or only an epiphenomenon.
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Affiliation(s)
- Pinar Karakaya
- *Pinar Karakaya, Department of Endocrinology and Metabolism, Bakırköy Dr. Sadi Konuk Training and Research Hospital, 34100 Istanbul, Turkey,
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Ahmad F, Zhou Y. Pitfalls and Challenges in Nanotoxicology: A Case of Cobalt Ferrite (CoFe 2O 4) Nanocomposites. Chem Res Toxicol 2017; 30:492-507. [PMID: 28118545 DOI: 10.1021/acs.chemrestox.6b00377] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Nanotechnology is developing at a rapid pace with promises of a brilliant socio-economic future. The apprehensions of vivid future involvement with nanotechnology make nanoobjects ubiquitous in the macroscopic world of humans. Nanotechnology helps us to visualize the new mysterious horizons in engineering, sophisticated electronics, environmental remediation, biosensing, and nanomedicine. In all these hotspots, cobalt ferrite (CoFe) nanoparticles (NPs) are outstanding contestants because of their astonishing controllable physicochemical and magnetic properties with ease of synthesis methods. The extensive use of CoFe NPs may result in CoFe NPs easily penetrating the human body unintentionally by ingestion, inhalation, adsorption, etc. and intentionally being instilled into the human body during biomedical diagnostics and treatment. After being housed in the human body, it might induce oxidative stress, cytotoxicity, genotoxicity, inflammation, apoptosis, and developmental, metabolic and hormonal abnormalities. In this review, we compiled the toxicity knowledge of CoFe NPs aimed to provide the safe usage of this breed of nanomaterials.
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Affiliation(s)
- Farooq Ahmad
- College of Chemical Engineering, Zhejiang University of Technology , Hangzhou 310032, China.,State Key Laboratory of Metal Matrix Composites, School of Material Science and Engineering, Shanghai Jiao Tong University , 800 Dongchuan Road, Shanghai 200240, China
| | - Ying Zhou
- College of Chemical Engineering, Zhejiang University of Technology , Hangzhou 310032, China.,Research Center of Analysis and Measurement, Zhejiang University of Technology , 18 Chaowang Road, Hangzhou 310032, China
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Ivanišević J, Kotur-Stevuljević J, Stefanović A, Spasić S, Vučinić Mihailović V, Videnović Ivanov J, Jelić-Ivanović Z. Association of serum amyloid A and oxidative stress with paraoxonase 1 in sarcoidosis patients. Eur J Clin Invest 2016; 46:418-24. [PMID: 26919159 DOI: 10.1111/eci.12610] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2015] [Accepted: 02/19/2016] [Indexed: 11/27/2022]
Abstract
BACKGROUND It has been reported that high-density lipoprotein (HDL) particles have anti-inflammatory and antioxidant roles thanks to different enzymes such as paraoxonase 1 (PON1). Under inflammatory and oxidative stress conditions, HDL particles may lose their protective properties. Sarcoidosis is an inflammatory disease characterized by excessive oxidative stress. Serum amyloid A (SAA) is produced in liver and in granulomas, and its concentration increases in inflammatory conditions contributing to increased catabolism of HDL particles. The aim of our study was to determine PON1 activity, SAA concentration and their associations in patients with sarcoidosis. MATERIALS AND METHODS Inflammatory [high-sensitive C-reactive protein (hsCRP), angiotensin-converting enzyme (ACE), SAA], lipid [total cholesterol (TC), HDL-cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triglycerides (TG)] oxidative stress status parameters [total oxidant status (TOS), malondialdehyde (MDA), pro-oxidant-antioxidant balance (PAB), sulfhydryl (SH) groups] and PON1 activities were determined in serum of 72 patients with sarcoidosis and 62 healthy subjects. RESULTS HsCRP (P < 0·05), TC, LDL-c, TG, SAA, TOS, MDA and PAB (P < 0·001) were significantly higher, whereas HDL-c, SH groups and PON1 activity (P < 0·001) were significantly lower in patients with sarcoidosis when compared with controls. PON1 showed significant association with SAA, MDA and PAB. It was shown that 71% of decrease in PON1 activity may be explained by increase in TOS, PAB and SAA concentration. CONCLUSIONS We found decreased PON1 activity and increased SAA concentration in patients with sarcoidosis. Inflammatory condition presented by high SAA was implicated in impaired HDL functionality evident through dysregulated PON1 activity. Excessive oxidative stress was also involved in dysregulation of PON1 activity.
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Affiliation(s)
- Jasmina Ivanišević
- Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
| | - Jelena Kotur-Stevuljević
- Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
| | - Aleksandra Stefanović
- Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
| | - Slavica Spasić
- Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
| | | | | | - Zorana Jelić-Ivanović
- Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
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Effect of Nutritionally Relevant Doses of Long-Chain N-3 Pufa on Lipid Status, Oxidative Stress and Inflammatory Markers in an Average Middle-Aged Serbian Population. J Med Biochem 2015; 34:304-313. [PMID: 28356841 PMCID: PMC4922342 DOI: 10.2478/jomb-2014-0039] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2014] [Accepted: 03/28/2014] [Indexed: 12/31/2022] Open
Abstract
Background This study investigated the effects of a nutritionally relevant intake of eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids derived from oily fish or a fish oil supplement on selected cardiovascular risk factors in average middle-aged individuals. Methods Thirty-three participants were randomized to receive salmon (oily fish) providing 274 mg EPA + 671 mg DHA/day or a commercial fish oil supplement providing 396 mg EPA + 250 mg DHA/day in a cross-over trial over an 8-week period separated by a 6-month washout period. Blood samples were collected before and after each intervention and lipids, inflammatory and oxidative stress parameters were determined. Results Plasma levels of EPA, DHA and total n-3 fatty acids significantly increased after both interventions. A decreasing trend in triglycerides was more pronounced with salmon than with the fish oil supplement, but the changes noticed were not significant. Although there were no relevant changes in inflammatory marker concentrations at the end of both interventions, significant negative correlations were noticed between total plasma n-3 fatty acids and soluble intercellular adhesion molecule and C-reactive protein throughout the whole intervention period (p<0.05). Among the oxidative stress parameters, intervention with salmon showed a prooxidative effect through a superoxide anion increase (p=0.025). A relevant positive correlation was also found between its concentration and total plasma n-3 fatty acids (p<0.05). Other oxidative stress markers were not significantly influenced by the dietary interventions applied. Conclusions Following two sets of recommendations for n-3 fatty acids intake aimed at the general public had only a moderate effect on the selected cardiovascular risk factors in average healthy middle-aged subjects over a short-term period.
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Dullaart RPF, Otvos JD, James RW. Serum paraoxonase-1 activity is more closely related to HDL particle concentration and large HDL particles than to HDL cholesterol in Type 2 diabetic and non-diabetic subjects. Clin Biochem 2014; 47:1022-7. [PMID: 24769273 DOI: 10.1016/j.clinbiochem.2014.04.013] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2014] [Revised: 03/19/2014] [Accepted: 04/11/2014] [Indexed: 01/01/2023]
Abstract
OBJECTIVES We determined relationships of the anti-oxidative enzyme, paraoxonase-1 (PON-1), with high density lipoprotein (HDL) subfractions, and tested whether these relationships are stronger than those with HDL cholesterol and apolipoprotein A-I (apoA-I) in subjects with and without type 2 diabetes mellitus (T2DM). DESIGN AND METHODS Serum PON-1 (arylesterase activity) and HDL subfractions (nuclear magnetic resonance spectroscopy) were determined in 67 T2DM patients and in 56 non-diabetic subjects. RESULTS PON-1 activity, HDL cholesterol and apoA-I were decreased in T2DM (all p<0.05). The HDL particle concentration was unaltered, but large HDL particles, medium HDL particles and HDL particle size were decreased, whereas small HDL particles were increased in T2DM (all p<0.05). PON-1 was more closely related to HDL cholesterol than to apoA-I (p=0.001). In turn, the positive relationship of PON-1 with the HDL particle concentration and with large HDL particles was stronger than that with HDL cholesterol (both p<0.01). The inverse relationship of PON-1 with T2DM was only modestly attenuated by HDL cholesterol or HDL particle characteristics. CONCLUSIONS PON-1 activity is more closely related to the HDL particle concentration or large HDL particles than to HDL cholesterol. Impaired PON-1 activity in T2DM is not to a considerable extent explained by altered HDL subfraction levels.
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Affiliation(s)
- Robin P F Dullaart
- Department of Endocrinology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
| | | | - Richard W James
- Division of Endocrinology, Diabetology, Hypertension and Nutrition, University Hospital Geneva, Switzerland.
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Kostapanos MS, Elisaf MS. High density lipoproteins and type 2 diabetes: Emerging concepts in their relationship. World J Exp Med 2014; 4:1-6. [PMID: 24977116 PMCID: PMC4073260 DOI: 10.5493/wjem.v4.i1.1] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2013] [Accepted: 11/16/2013] [Indexed: 02/05/2023] Open
Abstract
Patients with type 2 diabetes mellitus (T2DM) frequently exhibit macrovascular complications of atherosclerotic cardiovascular (CV) disease. High density lipoproteins (HDL) are protective against atherosclerosis. Low levels of HDL cholesterol (HDL-C) independently contribute to CV risk. Patients with T2DM not only exhibit low HDL-C, but also dysfunctional HDL. Furthermore, low concentration of HDL may increase the risk for the development of T2DM through a decreased β cell survival and secretory function. In this paper, we discuss emerging concepts in the relationship of T2DM with HDL.
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Lima VBDS, Sampaio FDA, Bezerra DLC, Moita Neto JM, Marreiro DDN. Parameters of glycemic control and their relationship with zinc concentrations in blood and with superoxide dismutase enzyme activity in type 2 diabetes patients. ACTA ACUST UNITED AC 2012; 55:701-7. [PMID: 22231973 DOI: 10.1590/s0004-27302011000900006] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2011] [Accepted: 11/04/2011] [Indexed: 02/04/2023]
Abstract
OBJECTIVE This study assessed the relationship between the parameters of glycemic control, and zinc concentrations in blood and superoxide dismutase enzyme activity in type 2 diabetes patients. SUBJECTS AND METHODS Seventy-three individuals, aged between 25 and 59 years, were divided into the experimental group (type 2 diabetes patients, n = 36) and control group (n = 37). Plasma and erythrocyte zinc concentrations, superoxide dismutase activity, and parameters of glycemic control were analyzed. RESULTS Mean plasma zinc concentration was 74.1 ± 10.7 µg/dL and 68.8 ± 9.6 µg/dL, erythrocyte zinc concentration was 48.1 ± 9.5 µg/gHb and 41.2 ± 8.0 µg/gHb, and superoxide dismutase activity was 2248.9 ± 300.0 U/gHb and 2059.6 ± 285.4 U/gHb, in the experimental group and the control group, respectively (p < 0.05). CONCLUSION Type 2 diabetes patients showed a positive response to oxidative stress due to adequate zinc concentration in blood and increased activity of superoxide dismutase, and the enzyme was influenced by serum insulin.
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Yucel Y, Celepkolu T, Kibrisli E, Kilinc F, Beyaz C, Ufuk Alucl M, Kemal Basa M, Ekinci A. Protective Effect of Caffeic Acid Phenethyl Ester on Oxidative Stress in
Diabetic Rat Sciatic Nerve. INT J PHARMACOL 2012. [DOI: 10.3923/ijp.2012.577.581] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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Mehdi MM, Rizvi SI. Human Plasma Paraoxonase 1 (PON1) Arylesterase Activity During Aging: Correlation with Susceptibility of LDL Oxidation. Arch Med Res 2012; 43:438-43. [DOI: 10.1016/j.arcmed.2012.08.012] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2012] [Accepted: 08/17/2012] [Indexed: 10/27/2022]
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Uzar E, Alp H, Cevik MU, Fırat U, Evliyaoglu O, Tufek A, Altun Y. Ellagic acid attenuates oxidative stress on brain and sciatic nerve and improves histopathology of brain in streptozotocin-induced diabetic rats. Neurol Sci 2011; 33:567-74. [PMID: 21922312 DOI: 10.1007/s10072-011-0775-1] [Citation(s) in RCA: 88] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2011] [Accepted: 08/31/2011] [Indexed: 01/18/2023]
Abstract
The aim of this study was to investigate the possible effects of ellagic acid in brain and sciatic nerve tissues of diabetic rats. Also, the impact of ellagic acid on catalase and paraoxonase (PON-1) activities, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), malondialdehyde (MDA) and nitric oxide (NO) were examined. The rats were randomly divided into four groups, with eight rats each: Normal controls (not diabetic), only ellagic acid treated (ellagic acid controls, not diabetic), Diabetic controls (streptozotocin, diabetic), ellagic acid-treated diabetic (streptozotocin + ellagic acid). After a 4 week experiment, rats were sacrificed, and biomarkers for oxidative stress in the brain and sciatic nerve tissues of the rats were measured. There was significant depletion in the PON-1, catalase, and TAS levels in the brain and sciatic nerve tissues compared to the control groups (for both parameters, p<0.05). The values of catalase, PON-1 and TAS reversed back to normal levels in ellagic acid-treated diabetic rats compared to untreated diabetic rats (for both parameters, p<0.05). The levels of MDA, TOS, NO and, OSI in the brain and sciatic nerve tissues were higher in untreated diabetic rats compared to control group (for both parameters p<0.05). However, MDA, TOS, OSI, and NO levels were found to be significantly reduced in the ellagic acid-treated diabetic group compared to the untreated diabetic group in these tissues (for both parameters, p<0.05). In conclusion, the results of the present study suggested that ellagic acid exhibits neuroprotective effects against oxidative damage in diabetic rats.
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Affiliation(s)
- Ertugrul Uzar
- Department of Neurology, Faculty of Medicine, Dicle University School of Medicine, 21280, Diyarbakır, Turkey.
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Moin DS, Rohatgi A. Clinical applications of advanced lipoprotein testing in diabetes mellitus. CLINICAL LIPIDOLOGY 2011; 6:371-387. [PMID: 22162979 PMCID: PMC3232732 DOI: 10.2217/clp.11.37] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Traditional lipid profiles often fail to fully explain the elevated cardiovascular risk of individuals with diabetes mellitus. Advanced lipoprotein testing offers a novel means to evaluate dyslipidemia and refine risk estimation. Numerous observational studies have demonstrated a characteristic pattern of elevated levels of small, dense LDL particles, out of proportion to traditional lipid levels, in patients with both diabetes mellitus and the metabolic syndrome. Commonly used glucose and lipid-lowering agents have varied effects in patients with diabetes on both LDL and HDL subfractions. The exact role of advanced lipoprotein testing in patients with diabetes mellitus and the metabolic syndrome remains unclear but may offer improved assessment of cardiovascular risk compared with traditional lipid measurements.
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Affiliation(s)
- Danyaal S Moin
- Department of Internal Medicine, University of Texas-Southwestern Medical Center, Dallas, TX, USA
| | - Anand Rohatgi
- Department of Internal Medicine, University of Texas-Southwestern Medical Center, Dallas, TX, USA
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Mahmoudi M, Azadmanesh K, Shokrgozar MA, Journeay WS, Laurent S. Effect of Nanoparticles on the Cell Life Cycle. Chem Rev 2011; 111:3407-32. [DOI: 10.1021/cr1003166] [Citation(s) in RCA: 237] [Impact Index Per Article: 16.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Morteza Mahmoudi
- National Cell Bank, Pasteur Institute of Iran, Tehran, 1316943551 Iran
- Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Kayhan Azadmanesh
- Virology Department, Pasteur Institute of Iran, Tehran, 1316943551 Iran
| | | | - W. Shane Journeay
- Nanotechnology Toxicology Consulting & Training, Inc., Nova Scotia, Canada
- Faculty of Medicine, Dalhousie Medical School, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Sophie Laurent
- Department of General, Organic, and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, Avenue Maistriau, 19, B-7000 Mons, Belgium
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