TY - JOUR
T1 - 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
AU - Groebler, Ludwig K.
AU - Wang, Xiao Suo
AU - Kim, Hyun Bo
AU - Shanu, Anu
AU - Hossain, Farjaneh
AU - McMahon, Aisling C.
AU - Witting, Paul K.
PY - 2012
Y1 - 2012
N2 - 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
AB - 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
KW - acute renal failure
KW - antioxidants
KW - burns
KW - myoglobinuria
KW - oxidative stress
KW - rhabdomyolysis
UR - http://handle.westernsydney.edu.au:8081/1959.7/uws:43176
U2 - 10.1016/j.freeradbiomed.2012.02.011
DO - 10.1016/j.freeradbiomed.2012.02.011
M3 - Article
SN - 0891-5849
VL - 52
SP - 1918
EP - 1928
JO - Free Radical Biology & Medicine
JF - Free Radical Biology & Medicine
IS - 9
ER -