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Tumor necrosis factor‐α supression rescues glutathione peroxidase activity in kidney of insulin resistant rats (1134.12)
Author(s) -
Carter Matthew,
Lee Andrew,
Rodriguez Ruben,
Thorwald Max,
Ortiz Rudy,
Nishiyama Akira
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1134.12
Subject(s) - endocrinology , medicine , glutathione peroxidase , chemistry , superoxide dismutase , catalase , candesartan , antioxidant , kidney , oxidative stress , angiotensin ii , receptor , biochemistry
The interactions between reactive oxygen species (ROS) production and kidney nephropathy in metabolic syndrome are not well described. This study assessed the effects of blocking 1) renin‐angiotensin system (RAS), 2) tumor necrosis factor‐alpha (TNFα)‐mediated inflammation, 3) and non‐RAS‐mediated hypertension on the activity of the antioxidant enzymes, glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) in the kidney of insulin resistant (IR), Otsuka‐Long‐Evans‐Tokushima‐Fatty (OLETF) rats. Lean and obese rats (n = 5‐7/group) were randomly assigned to the following groups: 1) untreated Long‐Evans‐Tokushima‐Otsuka (LETO) (lean, strain control ), 2) untreated OLETF, 3) OLETF + angiotensin receptor blocker (ARB) (10 mg olmesartan/kg/d x 10 wk), 4) OLETF + TNFα blocker (ETAN) (1.25 mg entanercept/kg/d x 10 wk), 5) OLETF + calcium channel blocker (CCB) (3 mg amlodipine/kg/d x 10 wk), and 6) OLETF + ARB+ ETAN (COMBO) (same doses x 10 wk). OLETF exhibited a 23% decrease (41 ± 4 vs. 32 ± 3 nmol/min/ml) in mean GPx activity. TNFα blockade completely recovered the IR‐associated decrease in GPx activity (45 ± 4 nmol/min/ml) demonstrating that TNFα contributes to the dysregulation of antioxidant enzymes in the IR kidney. Catalase and SOD activities, while elevated, were not different among groups suggesting that the dysregulation of antioxidant enzymes is selective during IR conditions. Grant Funding Source : APS Teacher Researcher