Protective Effect of Azadirachtha inidica and Vitamin E against Arsenic Acid- Induced Genotoxicity and Apoptosis in Rats

Abstract

Sodium arsenite is one of the major environmental toxicants with severe toxicological consequences in some developing and developed countries. Rats in Group A received normal saline. Genotoxicity and apoptosis were induced by single intraperitoneal injection of 10 mg/kg Sodium arsenite to rats in Groups B-F. Rats in Groups C and D had earlier been pretreated with Azadirachta indica (100 and 200 mg/kg) or E and F with vitamin E (50 and 100 mg/kg), respectively. Markers of oxidative stress, inflammation, hepatic damage, genotoxicity, and apoptosis were assessed. Pretreatment of rats with either Azadirachta indica or vitamin E led to a significant increase in the activities of glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH) in the liver compared to the group that received Sodium arsenite alone. Markers of oxidative stress and inflammation, malondialdehyde (MDA), hydrogen peroxide (H₂O₂) generation, nitric oxide (NO), and myeloperoxidase (MPO), were significantly lowered in rats pretreated with Azadirachta indica or vitamin E. The frequency of micronucleated polychromatic erythrocytes (MNPCEs) and expression of caspase-3 were significantly reduced in rats pretreated with either Azadirachta indica or vitamin E compared to rats intoxicated with arsenite. Histopathology of the liver showed areas of infiltration of inflammatory cells with death of numerous hepatocytes in Sodium arsenite intoxicated rats, and these were reversed by Azadirachta indica. Together, this study reports the genoprotective and antiapoptotic effect of Azadirachta indica by significant reduction in micronuclei formation, apoptosis, and oxidative stress induced by arsenic intoxication.