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

Ludwig K. Groebler, Xiao Suo Wang, Hyun Bo Kim, Anu Shanu, Farjaneh Hossain, Aisling C. McMahon, Paul K. Witting

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

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 F 2-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 kappabeta (NFκβ) gene expression and promoted AKI as judged by formation of tubular casts, damaged epithelia, and increased urinary levels of total protein, kidney-injurymolecule-1 (KIM-1), and clusterin. Supplementation with BP ± Vit C inhibited the two indices of lipid oxidation, down-regulated GPx-4, SOD1/2, and NF-κβ 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 watersoluble antioxidants may differ in terms of their therapeutic impact on RM-induced renal dysfunction
Original languageEnglish
Pages (from-to)1918-1928
Number of pages11
JournalFree Radical Biology & Medicine
Volume52
Issue number9
DOIs
Publication statusPublished - 2012

Keywords

  • acute renal failure
  • antioxidants
  • burns
  • myoglobinuria
  • oxidative stress
  • rhabdomyolysis

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