Oxidative stress predominates apoptosis during experimental hepatocellular carcinoma

Abstract

Objective Hepatocellular carcinoma ranks the third among cancer deaths in the globe. Despite the fact that many strategies for diagnosing liver cancer are possible, many factors, including apoptosis, arise to interfere with cell cycle control. We initiated this study to investigate the importance of free radicals during experimental hepatocarcinogenesis, triggered by diethyl nitrosamine, against an anti-apoptotic factor, belongs to a family of oncogenes (Bcl-2).
Methods Eighteen female Wistar rats were classified into two equal groups, group 1 received intraperitoneal normal saline doses, group 2 was injected with one IP dose of diethyl nitrosamine (200 mg/kg bw), 2 weeks later, they were given a single CCl4 dose (2 ml /kg b.w., IP), blood and liver tissue samples were collected after 60 days of diethyl nitrosamine dose. The Graph pad prism program was used in statistical calculations.
Results The results revealed that treatment with diethyl nitrosamine + CCl4 significantly up regulated the plasma liver functions tests: aspartate transaminase, alanine transaminase, gamma-glutamyl transpeptidase, total bilirubin and increased alpha fetoprotein with decreased level of Bcl-2. Liver tissue showed elevation of lipid peroxide, malondialdehyde, catalase enzyme activity, with significant reduction in body weight, decreased total protein content, tissue antioxidants like glutathione S-transferase, total thiol and total antioxidant capacity, compared to control. Histological examination of liver showed an increased nuclear/cytoplasm (N/C) ratio, mitotic figures and nuclear polymorphism and microacinar formation in diethyl nitrosamine + CCl4-treated group.
Conclusions Disturbed hepatocellular anti-oxidant mechanisms suppress apoptosis, reflecting failure in combating chemical
hepatocarcinogenesis.
Keywords liver cancer; diethyl nitrosamine; lipid peroxidation; tumor markers; Bcl-2; apoptosis.