Toxicology mechanisms and methods

Effect of Aegle marmelos on DEN initiated and 2-AAF promoted hepatocarcinogenesis: a chemopreventive study.

PMID 21417629


In this study, we examined the inhibitory effects of Aegle marmelos methanolic extract on diethylnitrosamine (DEN) initiated and 2-acetyl aminofluorene (2-AAF) promoted liver carcinogenesis in male Wistar rats. Interestingly, it was found that A. marmelos (25 and 50 mg/kg body weight) resulted in a marked reduction of the incidence of liver tumors, which was further confirmed with histopathology. Furthermore to understand the underlying mechanisms of chemoprevention potential of A. marmelos, we evaluated the levels of hepatic antioxidant defence enzymes, ornithine decarboxylase (ODC) activity and hepatic DNA synthesis as a marker for tumor promotion since a direct correlation between these marker parameters and carcinogenicity have been well documented. Treatment of male Wistar rats for five consecutive days with 2-AAF induced significant hepatic toxicity, oxidative stress and hyper-proliferation. Pretreatment of A. marmelos extract (25 and 50 mg/kg body weight) prevented oxidative stress and toxicity by restoring the levels of antioxidant enzymes at both the doses. The promotion parameters (ODC activity and DNA synthesis) induced by 2-AAF administration in diet with partial hepatectomy (PH) were also significantly suppressed dose-dependently by A. marmelos. Therefore, we can conclude that ultimately the protection against liver carcinogenesis by A. marmelos methanolic extract might be mediated by multiple actions, which include restoration of cellular antioxidant enzymes, detoxifying enzymes, ODC activity and DNA synthesis.