Quercetin attenuates chronic ethanol hepatotoxicity: Implication of free iron uptake and release

Emerging evidence has displayed that oxygen free radicals especially ones promoted by free iron play an important role in the development of alcoholic liver disease (ALD). Naturally-occurring quercetin has been reported to prevent ALD and iron overload-induced damage aside from the free iron. The purpose was to explore the potential mechanisms by which quercetin arrests alcohol-induced free iron disorder. Chronic alcohol (30% of total calories) or iron (0.2%)-fed adult male C57BL/J mice for 15 weeks resulted in significantly elevated levels of hepatic iron, labile iron pool-Fe and serum non-transferrin bound iron, accompanied with sustained oxidative damage. The hepatotoxicity was further exacerbated by ethanol and iron. Quercetin (100 mg/kg. body weight) alleviated the detrimental effects induced by ethanol and/or iron. The expressions of divalent metal transporter 1, zinc transporter member 14, mucolipin 1, transferrin receptor 1 (TfR1) and ferritin were up-regulated by ethanol and/or iron, which were partially normalized by quercetin. Quercetin prevented ethanol-induced hepatotoxicity, which may be partially attributed to the alleviated disorder of bound iron and free iron. The significant suppression of ethanol-stimulated molecules for free iron uptake and release may contribute to the hepatoprotective effect of quercetin, although TfR1-mediated physiological pathway of iron uptake also played a role. (C) 2014 Elsevier Ltd. All rights reserved.