Abstract
Introduction
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Medemia argun (MA) fruits have been found to possess proanthocyanidins (PACs), having antioxidant activity. Methods: Intraperitoneal (IP) diethyl nitrosamine (DENA; 200 mg/kg, once) and carbon tetra chloride (CCl4, 3 ml/kg/week, subcutaneously, for 6 weeks) induced HCC in rats. Animals groups: Group I; received vehicle (control). Group II; received MA seed extract, 100 mg/kg (twice/week) for 12 weeks, IP. Group III; received carcinogenic agents only. Group IV; received MA for two weeks before administration of DENA/CCl4 till the end of the experiment. The total period of the experiment was three months. Results: DENA and CCl4 induced HCC, elevated serum alpha-fetoprotein (AFP), liver size, weight, tissue lymphocytic infiltration, nuclear/cytoplasmic ratio, collagen fiber and polysaccharide deposition, cellular proliferation, excessive pro-apoptotic caspase-3 accumulation, disrupted apoptosis. MA prior to DENA/CCl4, significantly protected liver against cancer progression, indicated by serum enzymes, antioxidant markers(glutathione, nitric oxide, and depressed malondialdehyde contents) in the MA-pretreated group, compared to the HCC one, without apparent useful action on superoxide dismutase activity, enhanced apoptosis in liver, through increased casapase-3 expression. The HCC group showed decreased antioxidant defense and BAX/Bcl-2 ratio. Conclusions: This study assumes that MA has a chemo-preventive effect against hepatocarcinogenesis.
Author Contribution Statement
Nabil Mohie Abdel-Hamid: Suggested the concept and aims, reviewed draft, submitted the manuscript. Sara Gamal Abd Allah: Worked the whole experiments in collaboration with next authors. Mohamed K. Hassan: Executed the PCR work, supervised dosing, sampling, shared selection of parameters. Amal A.M. Ahmed: Executed the histological and immunostaining works. Nahla H. Anber: Shred the statistical analysis and interpretation of data. Ibrahim Abdel Faried: Provided the MA extract.
Conflict of Interest
Authors declare that no conflict of interest.
Financial Support and Sponsorship
This research did not receive any specific grant from funding bodies in the public, commercial, or not-for-profit sectors.