Ameliorated Effects of Verapamil on Hepatotoxicity Induced by Ethanol and Carbon Tetrachloride

Background: Liver fibrosis progresses to cirrhosis in several settings for example, alcoholic hepatitis and produce hepatocellular dysfunction, which is also a risk factor for hepatocellular carcinoma.Aim: This study was designated to investigate the potential toxicity of CCl 4 initiated by ethanol-as hepatotoxic agents on liver cellular structure glycogen, DNA contents and certain enzymes, and also to evaluate the preventive effect of a certain calcium ions antagonist like verapamil on carbon tetrachloride and ethyl alcohol-induced liver cellular injury in rats. Materials and methods:Sixty healthy adult male albino rats weighing from 200-220 grams were used in this study.Animals were divided into 4 groups, each consisted of 15 rats: the first was considered the normal control, Group 2 was considered the model control which was given ethanol and CCl 4 .Group 3,4 were considered the model control which was given verapamil with 2 doses; 40 and 80 mg.Samples of the liver were subjected to histopathological, histochemical ultrastructure and biochemical examinations after the restricted times.Results: Light microscopy revealed that rats given ethanol and CCl 4 combined together showed liver cell fibrosis and necrosis, nuclear fragmentation and inflammatory response.Glycogen disorder and DNA damage were also detected.On the other hand, animals that were given verapamil in two doses 40 and 80 reduced hepatocytes degeneration and necrosis, delayed formation of liver fibrosis was detected.There was marked improvement in hepatocytes architecture, glycogen and DNA contents.Electron microscopic and biochemical studies seem to confirm these findings. Conclusion:The present findings suggested that treatment with Verapamil significantly reverses hepatotoxic dysfunctions induced by CCl 4 and ethanol combination and it seems to be dose dependent.