Cosupplementation with a synthetic, lipid-soluble polyphenol and vitamin C inhibits oxidative damage and improves vascular function yet does not inhibit acute renal injury in an animal model of rhabdomyolysis

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• 作者：Ludwig K. Groebler^a ; Xiao Suo Wang^a ; Hyun Bo Kim^a ; Anu Shanu^a ; Farjaneh Hossain^a ; Aisling C. McMahon^b ; Paul K. Witting^a ; ^{p.witting@sydney.edu.au}
• 关键词：AKI ; acute kidney injury ; 尾-actin ; beta-actin ; CCL2/MCP-1 ; chemokine (C-C motif) ligand 2/monocyte chemotactic protein-1 ; CCr ; creatinine clearance ; CE ; cholesterylesters derived from linoleic and arachidonic acids ; CeO(O)H ; cholesterylester hydroperoxid
• 刊名：Free Radical Biology and Medicine
• 出版年：2012
• 期刊代码：105_08915849
• 类别：med
• 出版时间：1 May, 2012
• 卷：52
• 期：9
• 页码：1918-1928
• 文件大小：1073 K

摘要

We investigated whether cosupplementation with synthetic tetra-tert-butyl bisphenol (BP) and vitamin C (Vit C) ameliorated oxidative stress and acute kidney injury (AKI) in an animal model of acute rhabdomyolysis (RM). Rats were divided into groups: Sham and Control (normal chow), and BP (receiving 0.12%w/w BP in the diet; 4 weeks) with or without Vit C (100 mg/kg ascorbate in PBS ip at 72, 48, and 24 h before RM induction). All animals (except the Sham) were treated with 50%v/v glycerol/PBS (6 mL/kg injected into the hind leg) to induce RM. After 24 h, urine, plasma, kidneys, and aortae were harvested. Lipid oxidation (assessed as cholesteryl ester hydroperoxides and hydroxides and F₂-isoprostanes accumulation) increased in the kidney and plasma and this was coupled with decreased aortic levels of cyclic guanylylmonophosphate (cGMP). In renal tissues, RM stimulated glutathione peroxidase (GPx)-4, superoxide dismutase (SOD)-1/2 and nuclear factor kappa-beta (NF魏尾) gene expression and promoted AKI as judged by formation of tubular casts, damaged epithelia, and increased urinary levels of total protein, kidney-injury molecule-1 (KIM-1), and clusterin. Supplementation with BP 卤 Vit C inhibited the two indices of lipid oxidation, down-regulated GPx-4, SOD1/2, and NF-魏尾 gene responses and restored aortic cGMP, yet renal dysfunction and altered kidney morphology persisted. By contrast, supplementation with Vit C alone inhibited oxidative stress and diminished cast formation and proteinuria, while other plasma and urinary markers of AKI remained elevated. These data indicate that lipid- and water-soluble antioxidants may differ in terms of their therapeutic impact on RM-induced renal dysfunction.