Fisetin protects liver from binge alcohol-induced toxicity by mechanisms including inhibition of matrix metalloproteinases (MMPs) and oxidative stress

Abstract

Alcohol consumption is an addictive disorder causing hepatic steatosis, fibrosis and cirrhosis. The protective effect of fisetin, a bioflavonoid, present in foods like strawberries, apples, persimmons, grapes and onions was studied on murine model of acute alcohol-induced hepatotoxicity. Five doses of 50% ethanol p.o. (10 ml/kg body weight) every 12 hours was used to induce hepatotoxicity in mice. Liver function, oxidative stress, histological changes, mitochondrial function, pro-inflammatory markers, collagen content, and matrix metalloproteinases were assessed. Alcohol treatment produced a significant increase in the oxidative stress markers, disturbed the mitochondrial function, matrix metalloproteinases activities and also induced histological changes in liver tissue. Pre-treatment with fisetin (5 and 10 mg/kg) restored the alcohol-induced alterations in liver function, antioxidant defence, histological changes, mitochondrial respiratory enzymes and matrix metalloproteinases activities. Thus, fisetin has the potential to ameliorate alcohol-induced hepatic damage and may be used as an adjuvant in the treatment of alcohol-induced hepatotoxicity.

Keywords

• Alcohol-induced acute liver injury
• Fisetin
• Matrix metalloproteinases (MMPs)
• Oxidative stress
• Nuclear factor-kappa B (NF-κB)