Sequential proliferative lesions in the cirrhotic liver of rats: a histopathological and immunohistochemical study

Document Type : Original Article

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Department of Pathology, Faculty of Veterinary Medicine, Benha University, Egypt.

Abstract

Background/aim: Liver cirrhosis is a common health problem that is mostly at the late stage associated with hepatic carcinogenesis. This study aimed to clarify the sequentialproliferative lesions in the cirrhotic liver induced chemically by thioacetamide (TAA) in rats.
Methods: Thirty male albino rats were equally divided into control and TAA groups. In the TAA group, rats were intraperitoneally injected with 100 mg/kg TAA  twice /week for 18 weeks. Animals were euthanized after 6, 12, and 18 weeks. Blood and liver samples were collected for biochemical analysis and histopathological examination.
Results: TAA-treated group had significantly increased serum levels of liver damage parameters (alanine transaminase, aspartate transaminase, and alkaline phosphatase), and hepatic levels of oxidative stress-related markers (malondialdehyde and nitric oxide) as compared to the control group. Meanwhile, the TAA group showed significantly decreased hepatic levels of antioxidant markers (reduced glutathione and superoxide dismutase) relative to the control group. Histopathological examination of the liver revealed characteristic lesions of liver cirrhosis in form of regenerative nodules, the proliferation of bile ducts epithelium and hepatic stellate cells as well as different types of foci of cellular alterations which were prominent proliferative lesions in the liver of the TAA group. However, with TAA prolonged treatment, 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 following TAA treatment was interesting as it revealed a higher regeneration activity.
Conclusion: Some proliferative lesions such as regenerative nodules and foci of cellular alteration in hepatic cirrhosis may later constitute carcinogenic development.

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