Inhibitory effects of quercetin on aflatoxin B1-induced hepatic damage in mice.
Aflatoxin B(1) (AFB(1))-mediated hepatic damage is involved in production of AFB(1)-8,9-epoxide-bound DNA adducts and this is also affected by a pro-oxidant potential of the toxin. In this study we investigated the effects of quercetin on AFB(1)-treated HepG2 cells. We also examined the biochemical mechanisms associated with the effects of quercetin on AFB(1)-mediated liver damage in mice. Our results revealed that quercetin and isorhamnetin inhibit production of reactive oxygen species and cytotoxicity, and block the decrease of reduced glutathione (GSH) levels in AFB(1)-treated HepG2 cells. Isorhamnetin have inhibitory ability on lipid peroxidation stronger than quercetin in the cells. Oral supplementation with quercetin decreased serum lactate dehydrogenase levels, increased hepatic GSH levels and superoxide dismutase activity, and reduced lipid peroxidation in both the liver and kidney in AFB(1)-treated mice. However, quercetin did not show a significant reduction on serum levels of alkaline phosphate, alanine aminotransferase and aspartate aminotransferase that were increased in AFB(1)-treated mice. HPLC analysis revealed that quercetin in plasma is mainly present as glucoronides and/or sulfates of quercetin. Collectively, it is suggested that quercetin does not directly protect against AFB(1)-mediated liver damage in vivo, but exerts a partial role in promoting antioxidative defense systems and inhibiting lipid peroxidation.
Choi
K-C
KC
National Livestock Research Institute, RDA, Suweon 441-706, South Korea.
Chung
W-T
WT
Kwon
J-K
JK
Yu
J-Y
JY
Jang
Y-S
YS
Park
S-M
SM
Lee
S-Y
SY
Lee
J-C
JC
D016604:Aflatoxin B1 / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology / Q000517:prevention & control*; D002851:Chromatography, High Pressure Liquid; D044948:Flavonols / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009929:Organ Size / Q000187:drug effects; D011794:Quercetin / Q000494:pharmacology* / Q000031:analogs & derivatives; D017382:Reactive Oxygen Species / Q000378:metabolism
D044948:Flavonols; D017382:Reactive Oxygen Species; C047368:3-methylquercetin; D008315:Malondialdehyde; D011794:Quercetin; D016604:Aflatoxin B1; D005978:Glutathione