Chemopreventive and antioxidant activity by Smilax zeylanica leaf extract against N-nitrosodiethylamine induced hepatocarcinogenesis in wistar albino rats

摘要

The chemopreventive potential of methanol extract of Smilax zeylanica leaves against N-nitrosodiethylamine (NDEA) induced hepatocarcinogenesis was investigated in wistar albino male rats. The animals were divided into six groups. Group I served as normal control group, group II and group III served as extract control received Smilax zeylanica leaf extract 200 mg/kg and 400 mg/kg respectively once daily orally. A single intraperitoneal injection of NDEA (200 mg/kg) to group IV, group V and group VI animals followed by a single dose of carbon tetrachloride (CCl4, 2 ml/kg) 2 weeks later induced hepatocarcinogenesis in rats at the end of experimental period (16 weeks). Starting 1 week prior to NDEA administration, group V and group VI animals received methanol extract of Smilax zeylanica 200 mg/kg and 400 mg/kg respectively once daily orally for 16 weeks. At the end of the experimental period, the body weight, morphology of liver, relative liver weight, the levels of liver injury and liver cancer markers, the levels of lipid peroxidation and the activities of enzymatic and non-enzymatic antioxidants in liver tissue were assessed. Group IV NDEA induced hepatocarcinoma animals showed body weight loss with a significant increase in relative liver weight. The levels of liver injury and liver cancer markers such as alanine transaminase (AST), aspartate transaminase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), α-feto protein (AFT) and carcinoembryonic antigen (CEA) were substantially increased in group IV untreated animals. Moreover, with reference to lipid peroxidation and antioxidant system, group IV animals showed elevated levels of lipid peroxidation with a subsequent decrease in activities of antioxidant enzymes viz., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), glutathione-S-transferase (GST), glutathione (GSH), vitamin- C and vitamin-E in liver tissue. In contrast, the NDEA induced animals in group V and group VI treated with Smilax zeylanica leaf extract showed a significant improvement in body weight gain at the end of experimental period (16 weeks). A significant decrease in relative liver weight with reduced levels of liver injury and liver cancer markers in serum were observed in treatment groups. Moreover, treatment with Smilax zeylanica leaf extract decreased the extent of lipid peroxidation with concomitant increase in activities of enzymatic and non-enzymatic antioxidants when compared with NDEA induced untreated group IV animals. The histological observations of liver tissue too correlated the biochemical observations. Furthermore, the extract did not produce any deleterious effects in extract alone treated groups. These findings suggest that, the potential chemoprevention of methanol extract of Smilax zeylanica leaves might be due to stabilization and increase in all the components of antioxidant system attributed to antioxidant and free radical scavenging activity.