The Antioxidant Potential of Azadirachta indica Ameliorates Cardioprotection Following Diabetic Mellitus-Induced Microangiopathy

BACKGROUND: Cardiac complications associated with diabetes mellitus have become major cause of concern. Antidiabetic drugs, with varied mode of action, are although available, apprehensions exist for their limited action or side effects upon prolonged use. Efforts are therefore inclined toward finding other alternatives. The present study was, thus, undertaken to evaluate the cardioprotective effect of Azadirachta indica (AI) on microangiopathic changes in rat model of diabetes. MATERIALS AND METHODS: Diabetes was induced in male rats by single intraperitoneal injection of streptozotocin (60 mg/kg body weight). Seven days after glucose levels are stabilized, aqueous leaf extract of AI (ALE) (600 mg/kg(1) body weight) was administered orally to diabetic animals every day for 7 days. RESULTS: High blood glucose characterizing diabetes in these animals was found to show increased lipid peroxidation (LPO), altered antioxidant biomarkers together with microangiopathic alterations. The treatment of diabetic rats with ALE reduced the levels of blood glucose, LPO, and restored the activities of antioxidant enzyme. Light and transmission electron microscopic analysis revealed reduced necrotic areas and inflammation in tissue architecture of ALE treated heart in comparison to untreated diabetic group. CONCLUSION: AI provides cardioprotection by ameliorating oxidative stress in rat model of diabetic mellitus. SUMMARY: The streptozotocin (STZ) treatment (60 mg/kg body weight) to animals induced diabetic changes such as elevated blood glucose levels, decreased body weight, altered lipid profiles together with development of proxidant state evidenced by elevated levels of lipid peroxidation (LPO), depletion in reduced glutathione (GSH) levels and altered antioxidant enzymes with consequent microangiopathic alterations in heart tissue evinced by localization of necrotic and inflamed areas in heart tissue. The treatment of animals with Azadirachta indica leaf extract (ALE) (600 mg/kg body weight) post-STZ treatment significantly reversed the adverse effects witnessed by normalized blood glucose levels, improvement in reduced body weight and stabilized lipid profiles. Further, ALE treatment also significantly reduced the LPO indices, improvement in GSH content and restoration of antioxidant enzyme activities, suggesting antioxidatant potential of ALE. The microangiopathic changes in the heart tissue consequent to induction of diabetes and oxidative stress by STZ as reiterated through light microscopy and transmission electron microscopy were found to be reversed by ALE treatment. These observations pointed toward cardiopreventive effects of ALE following microangiopathic changes as seen following induction of diabetes mellitus. Abbreviations used: AI: Azadirachta indica, ALE: Azadirachta indica Leaves Extract. STZ: Streptozotocin, LPO Lipid per oxidation, GSH: Glutathione, GSSG: Glutathione disulphide, SOD: Superoxide dismutase, GP: Glutathione peroxidase, GR: Glutathione reductase.