AMELIORATIVE EFFECT OF METHANOLIC EXTRACT OF AZADIRACHTA INDICA LEAF ON LEAD ACETATE‐INDUCED CARDIOTOXOCITY, NEPHROTOXICITY AND GENOTOXICITY IN MALE WISTAR RATS

Abstract

The persistent existence of lead in the environment is associated with severe health issues due to its cumulative effect and its ability to affect virtually every organ in the body. Recent discoveries have attributed the tissue damaging and inflammatory effects of lead toxicity to oxidative stress. Natural antioxidants are now being employed in the alleviation of lead‐induced toxicity and oxidative stress as they have been observed to be effective with little or no side effects associated.This study is designed to investigate the ameliorative and antioxidative effects of Azadirachta indica on lead induced cardiotoxicity and nephrotoxicity. Cardiotoxicity and nephrotoxicity was established following oral administration of lead acetate (1mg/ml and 2mg/ml) for six weeks. However, rats were treated with 100mg/kg and 200mg/kg body weight of methanolic extract of Azadiracta indica (MEAI) after oral administration of lead acetate.Lead acetate administration led to a significant increase in heart rate, blood pressure and markers of oxidative stress in cardiac and renal tissues. Enzymic and non‐enzymic antioxidant defense systems were increased by lead acetate toxicity, there was however a persistent increase in glutathione‐S‐transferase (GST) activity. Renal nitric oxide (NO) content was significant reduced whereas cardiac NO content increased significantly. However, treatment of rats with 100mg/kg and 200mg/kg body weight of methanolic extract of Azadiracta indica (MEAI) after oral administration of lead acetate led to improvement in antioxidant defense systems, reduction in markers of oxidative stress, restoration of blood pressure and electrocardiographic (ECG) changes respectively. Lead acetate also precipitated genotoxicity which was significantly attenuated by MEAI. The pericardial inflammation and necrosis as well as the peritubular inflammation observed in the histology of the heart and kidney tissues. This architectural anarchy was ameliorated by MEAI.In conclusion, the results of this study show that Azadirachta indica ameliorated lead acetate‐induced cardiotoxicity and nephrotoxicity through free radical scavenging activity and antioxidant defense system. Furthermore, heart rate, systolic and diastolic pressure and other haemodynamic parameters were restored to near normal by MEAI. Hence, Azadirachta indica is a potential drug candidate against environmental pollutant such as lead acetate.