THE CHEMOTHERAPEUTIC ROLE OF p-MCA IN AVERTING NDEA INDUCED HEPATIC CARCINOGENESIS IN EXPERIMENTAL WISTAR RATS

Abstract

OBJECTIVES: Hepatocellular carcinoma (HCC) is the primary liver cancer and second leading cause of cancer related deaths worldwide. The aim of this present study was to evaluate the biochemical, histopathological and chemotherapeutic efcacy of p-methoxycinnamic acid (p-MCA) against N- nitrosodiethylamine (NDEA) in a rat model of hepatocellular carcinoma. MATERIALS AND METHODS: Approximately thirty male wistar rats weighing 150-200 g were designated for this study. The rats were arbitrarily separated into ve groups and each group comprised of six rats. Group 1 served as control; Group 2 rats received p-MCA at the dose of 80 mg/kg b.w. Group 3, 4 and 5 rats were induced HCC using NDEA. 2-acetylaminouorene (AAF) was used as a promotor. Group 4 and 5 rats received p-MCA at the doses of 40 and 80 mg/kg b.w. throughout the 12 week experimental period. At the end of the experimental period, liver tissues from all the rats were collected and liver specic enzymes, lipid peroxidation, markers, xenobiotic metabolizing enzymes, antioxidant status and brotic markers were evaluated.RESULTS: NDEA administration induced hepatocyte damage, oxidative stress, cell proliferation, inammation and brosis. The liver sections from NDEA induced group 3 rats showed loss of lobular architecture, morphological changes in the nuclei and DNA damage. Administration of p-MCA to NDEA treated rats restored the hepatic architecture, enzyme activities, cell proliferation, inammation and brosis.CONCLUSION: We conclude that oral administration of p-MCA for 12 weeks exerts a signicant therapeutic effect against HCC by regulating the concentration of specic hepatic and xenobiotic enzymes, suppressing oxidative stress, inhibiting cell proliferation and reducing the inammatory response.