Can the liver Regenerative Potential Restore the Normal Liver Structure in Male Mice CCL4 Induced Liver Fibrosis? A Histological and Immunohistochemical Study

Background: Liver fibrosis is a major Egyptian health problem and a serious threat to human health.It is characterized by repeated injury of the liver tissue resulting in the excessive accumulation of extracellular matrix. Liver is the only visceral organ that possesses unique capacity to regenerate.Aim of Work: To investigate the role of the regenerative capacity of the liver in restoring the normal structure after withdrawal of carbon tetrachloride (CCL4) in mice.Materials and Methods: A total number of thirty male healthy mice was used in the present study. The animals were randomly divided into three groups (10 mice each): Group І: (control group = GI).Group П: (CCL4 alone group = GII) were injected 1 ml/kg carbon tetrachloride (CCL4) dissolved in olive oil (1:1) twice a week for 4 weeks intraperitoneally . At the end of 4 weeks they were sacrificed. Group III (CCL4/recovery group=GIII): were injected with CCL4 as previous group, then left for another four weeks without any intervention before sacrifaction. At the end of the experiment, the liver was immediately dissected out and processed for histological and immunohistochemical examinations.Results: In GII, there was marked disturbance of liver architecture in the form of marked cellular infilteration and vacuolation associated with significant increase in the collagen and reticular fibers as well as increased expression of anti α-smooth muscle actin in hepatic stellate cells. Proliferative cells were observed in excess as indicated by increase in immunofluorescent staining of anti KI67. In GIII, moderate improvement was observed in liver architecture. Significant reduction in ALT and AST was also observed. On the other hand, serum albumin level was significantly increased compared to (GII).Conclusion: Withdrawal of CCL4 produced moderate improvement in the structure of the liver. As CCL4 chronic exposure exceeds the regenerative capacity of the liver to restore the normal structure