Protective effects of SP600125 in a diet-induced rat model of non-alcoholic steatohepatitis

Abstract

Objective. To investigate the protective effect of SP600125, a selective c-Jun N-terminal kinase inhibitor, in a diet-induced rat model of non-alcoholic steatohepatitis (NASH). Material and methods. Sprague–Dawley rats were randomly divided into three groups: a normal control group (NC group), a high-fat model group (HF group) and an SP600125 treatment group (SP group). All animals were subjected to a percutaneous superior mesenteric vein retention catheter operation and fed with a standard diet for 10 days. The HF group was then fed with an HF diet and treated with dimethyl sulfoxide while the SP group was fed with an HF diet and treated with SP600125 (50 mg/kg) once per day. Results. Feeding rats with an HF diet established a model of NASH, with varying degrees of hepatic steatosis and hepatic inflammation. SP600125 treatment substantially decreased the incidence of insulin resistance, reduced lipotoxicity, inhibited oxidative stress and alleviated hepatocellular injury. Conclusions. SP600125 has the potential to remarkably attenuate steatosis and inflammation and may be a novel therapeutic drug against NASH.

Key Words::

• Inflammation
• insulin resistance
• c-Jun N-terminal kinase
• non-alcoholic steatohepatitis
• oxidative stress
• SP600125