Prevention of peroxynitrite-induced renal injury through modulation of peroxynitrite production by the Chinese prescription Wen-Pi-Tang.
The effect of Wen-Pi-Tang extract on renal injury induced by peroxynitrite (ONOO-) production was investigated using rats subjected to intravenous lipopolysaccharide (LPS) injection and then renal ischemia followed by reperfusion. The plasma level of 3-nitrotyrosine, a marker of cytotoxic ONOO formation in vivo, was enhanced markedly in control rats subjected to LPS plus ischemia-reperfusion, but was significantly reduced by the oral administration of Wen-Pi-Tang extract, at doses of 62.5 and 125 mg/kg body weight/day, for 30 days prior to LPS plus ischemia-reperfusion. The activities of inducible nitric oxide synthase (iNOS) and xanthine oxidase (XOD) in renal tissue of control and Wen-Pi-Tang extract-treated rats did not change significantly, while those of the antioxidant enzymes, superoxide dismutase, catalase and glutathione peroxidase, were significantly increased by the administration of Wen-Pi-Tang extract, indicating that Wen-Pi-Tang improved the defense system by scavenging free radicals, not by directly inhibiting nitric oxide and superoxide production by iNOS and XOD. In addition, the levels of the hydroxylated products, m- and p-tyrosine, declined, whereas that of phenylalanine increased, after oral administration of Wen-Pi-Tang extract. Furthermore, the elevated plasma urea nitrogen and creatinine levels resulting from LPS plus ischemia-reperfusion process were significantly reduced by Wen-Pi-Tang extract, implying amelioration of renal impairment. The present study indicates that Wen-Pi-Tang extract contributes to the regulation of ONOO- formation and plays a beneficial role against ONOO(-) -induced oxidative injury and renal dysfunction in vivo.
Rhyu
Dong Young
DY
Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
Yokozawa
Takako
T
Choa
Eun Ju
EJ
Park
Jong Cheol
JC
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003404:Creatinine / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D007668:Kidney / Q000293:injuries* / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D008956:Models, Chemical; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009584:Nitrogen / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000009:adverse effects* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D014508:Urea / Q000097:blood; D014969:Xanthine Oxidase / Q000378:metabolism
D004365:Drugs, Chinese Herbal; D008054:Lipid Peroxides; D008070:Lipopolysaccharides; C474692:wen-pi-tang; D030421:Peroxynitrous Acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D014508:Urea; D003404:Creatinine; D019001:Nitric Oxide Synthase; D014969:Xanthine Oxidase; D009584:Nitrogen; D010100:Oxygen