scholarly journals GSTM1 Modulates Expression of Endothelial Adhesion Molecules in Uremic Milieu

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Djurdja Jerotic ◽  
Sonja Suvakov ◽  
Marija Matic ◽  
Abdelrahim Alqudah ◽  
David J. Grieve ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Antioxidant Enzyme ◽  
Adhesion Molecules ◽  
Antioxidant Enzyme Activities ◽  
Platelet Factor ◽  
Altered Expression ◽  
Monocyte Migration ◽  
Uremic Serum ◽  
Esrd Patients

Deletion polymorphism of glutathione S-transferase M1 (GSTM1), a phase II detoxification and antioxidant enzyme, increases susceptibility to end-stage renal disease (ESRD) as well as the development of cardiovascular diseases (CVD) among ESRD patients and leads to their shorter cardiovascular survival. The mechanisms by which GSTM1 downregulation contributes to oxidative stress and inflammation in endothelial cells in uremic conditions have not been investigated so far. Therefore, the aim of the present study was to elucidate the effects of GSTM1 knockdown on oxidative stress and expression of a panel of inflammatory markers in human umbilical vein endothelial cells (HUVECs) exposed to uremic serum. Additionally, we aimed to discern whether GSTM1-null genotype is associated with serum levels of adhesion molecules in ESRD patients. HUVECs treated with uremic serum exhibited impaired redox balance characterized by enhanced lipid peroxidation and decreased antioxidant enzyme activities, independently of the GSTM1 knockdown. In response to uremic injury, HUVECs exhibited alteration in the expression of a series of inflammatory cytokines including retinol-binding protein 4 (RBP4), regulated on activation, normal T cell expressed and secreted (RANTES), C-reactive protein (CRP), angiogenin, dickkopf-1 (Dkk-1), and platelet factor 4 (PF4). GSTM1 knockdown in HUVECs showed upregulation of monocyte chemoattractant protein-1 (MCP-1), a cytokine involved in the regulation of monocyte migration and adhesion. These cells also have shown upregulated intracellular and vascular cell adhesion molecules (ICAM-1 and VCAM-1). In accordance with these findings, the levels of serum ICAM-1 and VCAM-1 (sICAM-1 and sVCAM-1) were increased in ESRD patients lacking GSTM1, in comparison with patients with the GSTM1-active genotype. Based on these results, it may be concluded that incubation of endothelial cells in uremic serum induces redox imbalance accompanied with altered expression of a series of cytokines involved in arteriosclerosis and atherosclerosis. The association of GSTM1 downregulation with the altered expression of adhesion molecules might be at least partly responsible for the increased susceptibility of ESRD patients to CVD.

Role of thymoquinone and ebselen in the prevention of sodium arsenite–induced nephrotoxicity in female rats

2018 ◽  
Vol 38 (4) ◽  
pp. 482-493 ◽  
Author(s):  
AY Al-Brakati ◽  
RB Kassab ◽  
MS Lokman ◽  
EK Elmahallawy ◽  
HK Amin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzyme ◽  
Sodium Arsenite ◽  
Nigella Sativa ◽  
B Cell Lymphoma ◽  
Renal Tissue ◽  
Female Rats ◽  
Antioxidant Enzyme Activities ◽  
Significant Elevation ◽  
Nitrite Nitrate

The aim of this study is to investigate the protective effects of thymoquinone (TQ) and ebselen (Eb) on arsenic (As)-induced renal toxicity in female rats. Sodium arsenite was orally administrated at a dose of 20 mg/kg body weight daily for 28 days, either alone or 1 h before TQ (10 mg/kg) or Eb (5 mg/kg) administration. Renal tissue As concentration and oxidative stress markers, including lipid peroxidation (LPO), nitrite/nitrate, and glutathione (GSH) levels, were determined. In addition to the oxidative stress response, antioxidant enzyme activities including that of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were measured. Exposure to As elicited a significant increase in As concentration and significant modifications to the redox state of the kidney, as was evidenced by a significant elevation in LPO and nitrite/nitrate concentration, with a concomitant reduction in GSH content and antioxidant enzyme activity. The oxidant/antioxidant imbalance observed in As toxicity was associated with a significant elevation in renal tumor necrosis factor α, interleukin 6, B-cell lymphoma 2 (Bcl-2)-associated X protein, and caspase 3 levels, in addition to a significant decrease in Bcl-2 levels. Post-administration of TQ and Eb markedly prevented As-induced oxidative stress, inflammation, apoptosis, and As accumulation in the renal tissue and reduced histological renal damage. These findings demonstrate that TQ, the main bioactive phytochemical constituent of Nigella sativa seed oil, and Eb, an organoselenium compound, could significantly inhibit As-induced oxidative damage, apoptosis, and inflammation, and significantly attenuate the accumulation of As in renal tissues by facilitating As biomethylation and excretion.

scholarly journals Antioxidants and selenocompounds inhibit 3,5-dimethylaminophenol toxicity to human urothelial cells

2019 ◽  
Vol 70 (1) ◽  
pp. 18-29 ◽  
Author(s):  
Pinar Erkekoglu ◽  
Ming-Wei Chao ◽  
Chia-Yi Tseng ◽  
Bevin P. Engelward ◽  
Ozge Kose ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bladder Cancer ◽  
Antioxidant Enzyme ◽  
Enzyme Activities ◽  
Mammalian Cells ◽  
Antioxidant Enzyme Activities ◽  
Urothelial Cells ◽  
Dna Breaks ◽  
Primary Metabolite ◽  
Stress Changes

AbstractExposure to alkyl anilines may lead to bladder cancer, which is the second most frequent cancer of the urogenital tract. 3,5-dimethylaniline is highly used in industry. Studies on its primary metabolite 3,5-dimethylaminophenol (3,5-DMAP) showed that this compound causes oxidative stress, changes antioxidant enzyme activities, and leads to death of different mammalian cells. However, there is no in vitro study to show the direct effects of 3,5-DMAP on human bladder and urothelial cells. Selenocompounds are suggested to decrease oxidative stress caused by some chemicals, and selenium supplementation was shown to reduce the risk of bladder cancer. The main aim of this study was to investigate whether selenocompounds organic selenomethionine (SM, 10 µmol/L) or inorganic sodium selenite (SS, 30 nmol/L) could reduce oxidative stress, DNA damage, and apoptosis in UROtsa cells exposed to 3,5-DMAP. 3,5-DMAP caused a dose-dependent increase in intracellular generation of reactive oxygen species, and its dose of 50 µmol/L caused lipid peroxidation, protein oxidation, and changes in antioxidant enzyme activities in different cellular fractions. The comet assay also showed single-strand DNA breaks induced by the 3,5-DMAP dose of 50 µmol/L, but no changes in double-strand DNA breaks. Apoptosis was also triggered. Both selenocompounds provided partial protection against the cellular toxicity of 3,5-DMAP. Low selenium status along with exposure to alkyl anilines can be a major factor in the development of bladder cancer. More mechanistic studies are needed to specify the role of selenium in bladder cancer.

Antioxidant enzyme activities and oxidative stress in human breast cancer

1994 ◽  
Vol 120 (6) ◽  
pp. 374-377 ◽  
Author(s):  
K. Punnonen ◽  
M. Ahotupa ◽  
K. Asaishi ◽  
M. Hy�ty ◽  
R. Kudo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Antioxidant Enzyme ◽  
Enzyme Activities ◽  
Human Breast Cancer ◽  
Antioxidant Enzyme Activities ◽  
Human Breast ◽  
And Oxidative Stress

scholarly journals Effects of α-Tocopherol and Mixed Tocopherol Supplementation on Markers of Oxidative Stress and Inflammation in Type 2 Diabetes

2007 ◽  
Vol 53 (3) ◽  
pp. 511-519 ◽  
Author(s):  
Jason HY Wu ◽  
Natalie C Ward ◽  
Adeline P Indrawan ◽  
Coral-Ann Almeida ◽  
Jonathan M Hodgson ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Vitamin E ◽  
Antioxidant Enzyme ◽  
Enzyme Activities ◽  
Ex Vivo ◽  
Controlled Trial ◽  
Antioxidant Enzyme Activities ◽  
Markers Of Oxidative Stress

Abstract Background: Vitamin E isomers may protect against atherosclerosis. The aim of this study was to compare the effects of supplementation with either α-tocopherol (αT) or mixed tocopherols rich in γ-tocopherol (γT) on markers of oxidative stress and inflammation in patients with type 2 diabetes. Methods: In a double-blind, placebo-controlled trial, 55 patients with type 2 diabetes were randomly assigned to receive (500 mg/day) (a) αT, (b) mixed tocopherols, or (c) placebo for 6 weeks. Cellular tocopherols, plasma and urine F2-isoprostanes, erythrocyte antioxidant enzyme activities, plasma inflammatory markers, and ex vivo assessment of eicosanoid synthesis were analyzed pre- and postsupplementation. Results: Neutrophil αT and γT increased (both P <0.001) with mixed tocopherol supplementation, whereas αT (P <0.001) increased and γT decreased (P <0.005) after αT supplementation. Both αT and mixed tocopherol supplementation resulted in reduced plasma F2-isoprostanes (P <0.001 and P = 0.001, respectively) but did not affect 24-h urinary F2-isoprostanes or erythrocyte antioxidant enzyme activities. Neither αT nor mixed tocopherol supplementation affected plasma C-reactive protein, interleukin 6, tumor necrosis factor-α, or monocyte chemoattractant protein-1. Stimulated neutrophil leukotriene B4 production decreased significantly in the mixed tocopherol group (P = 0.02) but not in the αT group (P = 0.15). Conclusions: The ability of tocopherols to reduce systemic oxidative stress suggests potential benefits of vitamin E supplementation in patients with type 2 diabetes. In populations with well-controlled type 2 diabetes, supplementation with either αT or mixed tocopherols rich in γT is unlikely to confer further benefits in reducing inflammation.

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