title: 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.
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 (100mg/kg ascorbate in PBS ip at 72, 48, and 24h 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 24h, 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 kappa-beta (NFκβ) 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±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 water-soluble antioxidants may differ in terms of their therapeutic impact on RM-induced renal dysfunction.
authors.affiliation: Discipline of Pathology, Redox Biology Group and Bosch Institute, The University of Sydney, Sydney, New South Wales 2006, Australia.
authors.forename: Ludwig K
authors.initials: LK
authors.lastname: Groebler
authors.forename: Xiao Suo
authors.initials: XS
authors.lastname: Wang
authors.forename: Hyun Bo
authors.initials: HB
authors.lastname: Kim
authors.forename: Anu
authors.initials: A
authors.lastname: Shanu
authors.forename: Farjaneh
authors.initials: F
authors.lastname: Hossain
authors.forename: Aisling C
authors.initials: AC
authors.lastname: McMahon
authors.forename: Paul K
authors.initials: PK
authors.lastname: Witting
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D001483:Base Sequence; D015415:Biomarkers / Q000378:metabolism; D001808:Blood Vessels / Q000187:drug effects* / Q000502:physiology; D017931:DNA Primers; D007674:Kidney Diseases / Q000209:etiology*; D008055:Lipids / Q000737:chemistry*; D008297:Male; D023421:Models, Animal; D018384:Oxidative Stress; D059808:Polyphenols / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012206:Rhabdomyolysis / Q000150:complications*
chemical_list: D015415:Biomarkers; D017931:DNA Primers; D008055:Lipids; D059808:Polyphenols; D001205:Ascorbic Acid