liver cirrhosis is common health problem that mostly at late stage associated with hepatic carcinogenesis. So we carried this study to clarify the sequential proliferative lesions in cirrhotic liver, thirty male albino rats were divided into two equal groups; control and thioacetamide (TAA). In the latter group rats were treated with TAA 100 mg/kg, (i.p.) twice /week for 18 weeks. Rats were sacrificed after 6, 12 and 18 weeks, blood and liver samples were collected for biochemical analysis and histopathological examination, respectively. TAA treatment significantly increased alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), malondialdehyde (MDA) and nitric oxide (NO). Meanwhile, reduced glutathione(GSH) and super oxide dismutase(SOD)showed significant decrease comparing to control rats. Histopathological examination of the liver revealed characteristic lesions of liver cirrhosis. Regenerative nodules, proliferation of bile ducts epithelium, hepatic stellate cells and different types of foci of cellular alterations which were prominent proliferative lesions in cirrhotic livers of TAA treated rats. However, with prolonged treatment using TAA, cellular atypia and preneoplastic changes became evident in many hepatocytes. Immunohistochemical expression for Ki67 revealed positive nuclear labeling in some hepatocytes of TAA treated rats. Marked expression for Ki67 in regenerating nodules at 18 weeks post TAA treatment were interesting as it revealed a higher regeneration activity. The present study concluded that some proliferative lesions such as regenerative nodules and foci of cellular alteration may later constitute carcinogenic development.
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