ABSTRACT
Hepatocellular carcinoma is likely to become an increasingly significant challenge to health care industry in the coming decades. Hepatocarcinogenesis represents a linear and progressive process in which successively more aberrant monoclonal populations of hepatocytes evolve. This study was conducted to; I-Investigate the effectiveness of shark liver oil extract on rat liver during chemical- induced hepatocarcinogenesis for its possible protective effect against carcinogenesis, P- Glycoprotein expression and deterioration in liver function. 2- Evaluate morphological changes of the liver during hepatocarcinogenesis before and after treatment with of shark liver oil extract, and 3- Evaluate the pathogenetic role of p53 in liver carcinogenesis. The material of the present study constituted ninety male albino rats at the age of 2 months. Ten rats were used as controls. Carcinogenesis was induced in eighty rats by the administration of single dose of Diethyl Nitrosamine followed by three doses of 2-acetylaminofluorine and single dose of carbon tetrachloride. Rats were then divided into two equal groups; untreated, and treated with shark liver oil. Liver function tests were evaluated for all test rats. Livers of sacrificed animals were examined for morphological abnormalities, and were immunohistochemically stained for P-Glycoprotein [multi-drug resistance molecule] and p-53 [tumour suppressor gene] using avidin-biotin method. Statistical analysis was performed to compare the liver function tests, morphological alterations in the tested rat's liver and P-glycoprotein expression before and after administration of shark liver oil. Liver function tests were impaired in carcinogen-injected untreated rats, and then showed statistically significant improvements in shark liver oil -treated rats. Histological evaluation of carcinogen-injected untreated rat's liver, revealed number of combined liver cell changes in the form of; steatosis [86%], nodular regenerative hyperplasia [79%], liver cell dysplasia [71%], micronodular cirrhosis [7%], and different cholangiocellular changes [7-40%]. Hepatocellular carcinoma was not noted in any of tested groups. These morphological abnormalities and P-Glycoprotein expression showed statistically significant improvements in SLO-treated rats in comparison to untreated group. P53 was negative in all tested groups. Conclusion: Hepatocarcinogenesis evolutes through multistep process including many preneoplastic changes as liver cell dysplasia, and regenerative nodular hyperplasia as vell as cholangiolar cell abnormalities, and steatosis that are of indefinite significance. p53 has no role in early stages of hepatocarcinogenesis. Shark liver oil administration has protective effect against the process of chemical hepatocarcinogenesis verified by the improvement of deteriorated liver function tests, reduction of the preneoplastic features in tested livers. Shark liver oil administration reduces the expression of multidrug resistance molecule P-Glycoprotein