Pentoxifylline attenuates hepatic fibrosis by inhibiting hepatic stellate cells

What is it about?

Hepatic fibrosis is prevalent worldwide and it may proceed to cirrhosis and hepatocellular carcinoma. Its prevention is of high priority so as to reduce the consequent morbidity and mortality. Aim This study was conducted to investigate the efficiency of the antifibrotic effect of pentoxifylline (PTX) on carbon tetrachloride (CCL4)-induced hepatic fibrosis in a rat model. Materials and methods Thirty adult male rats were divided into three groups: the control group, the CCL4- treated group, and the PTX+CCL4-treated group. CCL4 (0.5 mg/kg) was injected intraperitoneally twice per week. An intrapritoneal injection of PTX (8 mg/kg) was started 2 weeks before CCL4 treatment and was administered concomitantly with CCL4 treatment for another 6 weeks.

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Why is it important?

After 8 weeks from CCL4 treatment, samples from the liver were prepared for histological and immunohistochemical study. Blood samples were analyzed for liver enzymes and albumin. The semiquantitative Masson’s fibrotic and alpha smooth muscle actin (ASMA) scores and their area% were measured morphometrically and analyzed statistically. Results In the CCL4-treated group, there was necroinflammatory reaction, with predominant severe necrosis and macrovesicular fatty degeneration. Extensive collagen deposition was mainly perivenular and extended to the portal tract in the form of marked bridging. The fibrosis and ASMA scores and their area% were highly significantly increased in comparison with the control group. In the PTX+CCL4-treated group, there was regression of the hepatic fibrosis and minimal affection of the hepatic lobule. Occasional vacuolar degeneration together with minimal perivenular collagen deposition was observed. The fibrosis and ASMA scores and their area% were highly significantly decreased in comparison with the CCL4-treated group. PTX could efficiently hinder hepatic fibrosis in CCL4 model. Conclusion In CCL4 model for hepatic fibrosis, PTX showed a beneficial effect by reducing fibrosis and suppressing hepatic stellate cells. Therefore, it could be a first choice antifibrotic for alleviation of hepatic fibrosis.

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