Effects of naringenin on fibrotic markers (MMPs and TIMP1) during ethanol induced hepatotoxicity

Abstract

To investigate the antifibrotic effects of naringenin on liver fibrosis induced on exposure to ethanol in rats. Rats were divided into four groups, groups 1 and 2 received isocaloric glucose and 0.5% carboxymethyl cellulose (CMC); groups 3 and 4 received 20% ethanol equivalent to 6g/kg body weight everyday for the total experimental period of 60 days. In addition, groups 2 and 4 were supplemented with naringenin (50mg/kg p.o) everyday for the last 30 days of the experiment. The results showed significantly elevated levels/activities/expression of serum aspartate and alanine transaminases, matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) in ethanol fed rats as compared to those of the control. Ethanol administration caused liver damage and fibrosis as evidenced by liver histology and various fibrogenic factors. Supplementation with naringenin for the last 30 days of the experiment to ethanol-fed rats, significantly decreased the activities/expression of serum aspartate and alanine transaminases, MMP2, MMP9 and TIMP1 in the liver as compared to the control rats. These findings suggest that naringenin has protective effect on liver injury and can inhibit liver fibrosis induced by ethanol in rats. Naringenin improved the histological changes of fibrosis. The mechanism possibly involves its anti-inflammatory activity associated with its effect on inhibiting MMP2, MMP9 and TIMP1and suppressing the activation of hepatic stellate cells.