Quercetin metabolites and protection against peroxynitrite-induced oxidative hepatic injury in rats.
Quercetin has strong antioxidant potency. Quercetin-3'-O-sulphate (Q3'S) and quercetin-3-O-glucuronide (Q3GA) are the main circulating metabolites after consumption of quercetin-O-glucoside-rich diets by humans. However, information about how these quercetin metabolites function in vivo is limited. Hence, this study evaluated the efficacy of Q3'S and Q3GA for the protection of oxidative injury using in vitro and in vivo experiments. Peroxynitrite-mediated hepatic injury in rats was induced by administration of galactosamine/lipopolysaccharide (GalN/LPS). Twenty-four hours after GalN/LPS treatment, plasma ALT and AST levels delta increased significantly. However, pretreatment with 4(G)-alpha-D-glucopyranosyl rutin, a quercetin glycoside (30 mg/kg body weight), prevented these increases and reduced nitrotyrosine formation, indicating that consumption of quercetin glycosides prevent oxidative hepatotoxicity. Moreover, physiological levels of Q3'S and Q3GA (1 microM) effectively prevented peroxynitrite-induced nitrotyrosine formation in human serum albumin in in vitro experiments. These findings indicate peroxynitrite-induced oxidative hepatotoxicity is protected by the in vivo metabolites of quercetin, Q3'S and Q3GA.
Yokoyama
Akiyuki
A
Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka, Japan.
Sakakibara
Hiroyuki
H
Crozier
Alan
A
Kawai
Yoshichika
Y
Matsui
Asako
A
Terao
Junji
J
Kumazawa
Shigenori
S
Shimoi
Kayoko
K
D000818:Animals; D005688:Galactosamine / Q000494:pharmacology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D030421:Peroxynitrous Acid / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011794:Quercetin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D008070:Lipopolysaccharides; D030421:Peroxynitrous Acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D005688:Galactosamine; D011794:Quercetin