Inhibition of NF-κB activation by diethylcarbamazine prevents alcohol-induced liver injury in C57BL/6 mice

Induction of NF-kappa B-mediated gene expression has been identified in the pathogenesis of alcoholic liver disease (ALD). Diethylcarbamazine (DEC) is a piperazine derivative drug with anti-inflammatory properties. The present study was designed to evaluate the effect of DEC on NF-kappa B pathways in mice undergoing alcoholism induced hepatic inflammation. Forty male C57BL16 mice were divided equally into four groups: control group (C); DEC-treated group, which received 50 mg/kg (DEC50); alcoholic group (Et0H), submitted to chronic alcohol consumption and the alcohol-DEC treated group (Et0HSO), submitted to chronic alcoholism consumption plus DEC treatment. Histological analysis of the alcoholic group showed evident hepatocellular damage which was reduced in EtOH50 group. Immunohistochemistry and western blot results showed elevated expression of inflammatory markers such as MDA, TNF-ce., IL-1 p, COX-2 and iNOS in hepatocytes of EtOH group. However, low immunopositivity for these markers was detected following DEC treatment. In the EtOH group the activation of NF-kappa B was observed by an increase in the expression of both NF-kappa B and pNF-kappa B in hepatocytes. This expression was significantly reduced in livers of EtOH50 group. Protein expression of IKI3ci was measured to determine whether activation of NF-kappa B might be the result of IK13c1 degradation. It was observed that expression of this protein was low in EtOH group, while animals treated with DEC had a high expression of I kappa beta alpha. The results of the present study indicate that DEC alleviates alcoholic liver injury, in part by the inhibiting activation of NF-kappa B and by suppressing the induction of NF-kappa B-dependent genes. 2014 Elsevier Ltd. All rights reserved.