Probucol attenuates ethanol-induced liver fibrosis in rats by inhibiting oxidative stress, extracellular matrix protein accumulation and cytokine production

Abstract

1. Liver fibrosis is characterized by excessive accumulation of extracellular matrix (ECM) proteins in the liver. Probucol, a lipid-lowering drug, was found to prevent liver injury in rats treated with carbon tetrachloride (CCl4 ). In the present study, we investigated whether probucol has protective effect against liver fibrosis in rats treated with ethanol and CCl4 . 2. Thirty rats were randomly divided into five groups. Groups I and II served as the normal control and the model of liver fibrosis, respectively. Groups III-V were treated with probucol at a doses of 250, 500 and 1000 mg/kg, respectively. Rats in Group II were fed a complex diet that includes alcohol, corn oil and pyrazole, and were injected intraperitoneally with CCl4 to induce hepatic fibrosis. Blood was obtained to assess markers of liver function. Liver samples were collected to evaluate mRNA and protein expression, histological changes and oxidative stress. 3. Probucol significantly attenuated the histological changes induced by ethanol + CCl4 and improved liver function. Expression levels of α-smooth muscle actin and collagen I was decreased in the probucol-treated groups. Moreover, probucol markedly suppressed increases in oxidative stress, ECM protein accumulation and cytokine production induced by ethanol + CCl4 . Finally, probucol inhibited activation of the extracellular signal-regulated kinase signalling pathway induced by ethanol + CCl4 . 4. Our findings reveal that probucol attenuates ethanol + CCl4 -induced liver fibrosis by inhibiting oxidative stress, ECM protein accumulation and cytokine production. These data suggest that probucol may be useful for the prevention and treatment of hepatic fibrosis.