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Dietary Fisetin Supplementation Protects Against Alcohol‐Induced Liver Injury in Mice
Author(s) -
Sun Qian,
Zhang Wenliang,
Zhong Wei,
Sun Xinguo,
Zhou Zhanxiang
Publication year - 2016
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.13172
Subject(s) - fisetin , liver injury , chemistry , endocrinology , oxidative stress , medicine , alcoholic liver disease , steatosis , pharmacology , alcohol dehydrogenase , lipid peroxidation , biochemistry , alcohol , antioxidant , flavonoid , cirrhosis
Background Overproduction of reactive oxygen species is associated with the development of alcoholic liver disease ( ALD ). Plant polyphenols have been used as dietary interventions for multiple diseases including ALD . The objective of this study was to determine whether dietary supplementation with fisetin, a novel flavonoid, exerts beneficial effect on alcohol‐induced liver injury. Methods C57 BL /6J mice were pair‐fed with the Lieber‐DeCarli control or ethanol (EtOH) diet for 4 weeks with or without fisetin supplementation at 10 mg/kg/d. Results Alcohol feeding induced lipid accumulation in the liver and increased plasma alanine aminotransferase and aspartate aminotransferase activities, which were attenuated by fisetin supplementation. The EtOH concentrations in the plasma and liver were significantly elevated by alcohol exposure but were reduced by fisetin supplementation. Although fisetin did not affect the protein expression of alcohol metabolism enzymes, the aldehyde dehydrogenase activities were significantly increased by fisetin compared to the alcohol alone group. In addition, fisetin supplementation remarkably reduced hepatic NADPH oxidase 4 levels along with decreased plasma hydrogen peroxide and hepatic superoxide and 4‐hydroxynonenal levels after alcohol exposure. Alcohol‐induced apoptosis and up‐regulation of Fas and cleaved caspase‐3 in the liver were prevented by fisetin. Moreover, fisetin supplementation attenuated alcohol‐induced hepatic steatosis through increasing plasma adiponectin levels and hepatic protein levels of p‐ AMPK , ACOX 1, CYP 4A, and MTTP . Conclusions This study demonstrated that the protective effect of fisetin on ALD is achieved by accelerating EtOH clearance and inhibition of oxidative stress. The data suggest that fisetin has a therapeutical potential for treating ALD .