Protective Effects of Ethanolic Neem Leaf Extract on N-Methyl-N′-nitro-N-nitrosoguanidine-Induced Genotoxicity and Oxidative Stress in Mice

We evaluated the effects of pretreatment with ethanolic neem leaf extract on N-methyl-N′-nitro-N-nitrosoguanidine (MNNG)-induced genotoxicity and oxidative stress in male Swiss albino mice. The frequency of micronuclei (MN), concentrations of lipid peroxides and the status of the antioxidants, reduced glutathione (GSH), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) were used as intermediate biomarkers of chemoprotection. Animals were divided into four groups of five animals each. Animals in group 1 were given MNNG (40 mg kg body weight) by intragastric intubation. Animals in group 2 received intragastric administration of ethanolic neem leaf extract at a concentration of 200 mg kg body weight for 5 days followed by MNNG 1.5 h after the final feeding. Group 3 animals received ethanolic neem leaf extract alone for five days. Group 4 received the same volume of normal saline and served as control. The animals were sacrificed by cervical dislocation 27 h after the carcinogen exposure. In MNNG-treated mice, enhanced lipid peroxidation with compromised antioxidant defences in the stomach, liver and erythrocytes was accompanied by increase in bone marrow micronuclei. Pretreatment with ethanolic neem leaf extract significantly reduced MNNG-induced micronuclei and lipid peroxides and enhanced GSH-dependent antioxidant activities. The results of the present study demonstrate that ethanolic neem leaf extract exerts protective effects against MNNG-induced genotoxicity and oxidative stress by augmenting host antioxidant defence mechanisms.