Ischemic-Postconditioning Improves Myocardial Injury and Fibrosis Following Ischemia/Reperfusion Injury in Diabetic Rats Pretreated with Alpha-Lipoic Acid

Abstract

Background: Myocardial ischemia/reperfusion (I/R) injury is one of the pre-eminent causes of death. Prevention of I/R injury in diabetic patients is full of ups and downs. This study has investigated the effect of co-administration of alpha-lipoic acid (ALA) preconditioning and ischemic-postconditioning (Post) on myocardial injury and fibrosis in type-II diabetic rats suffering from I/R injury. Methods: Chronic diabetes was induced by a high-fat supplemented diet and low-dose streptozotocin within 3 months. Diabetic rats received ALA (100 mg/kg/d, orally) for 5 weeks before I/R induction. The myocardium underwent 35 minutes of ischemia through left anterior descending (LAD) coronary artery ligation and 60 minutes of reperfusion. Post was consisted of six cycles of 10/10 seconds algorithm and applied in the early stage of reperfusion. The release of creatine kinase (CK) as the injury enzyme was measured with ELISA. The protein expression of fibrosis markers was evaluated with western blotting and tissue fibrosis was scored through Masson’s trichrome staining. Results: Post alone had no considerable effect on cardiac injury marker CK, while ALA had somehow a positive impact. However, the application of Post in ALA-pretreated rats significantly reduced the injury marker in comparison with the untreated I/R group. In addition, this combination therapy decreased Smad3 and transforming growth factor-β (TGF-β) expression and improved tissue fibrosis as compared with the untreated group. Conclusion: Combination of ALA pretreatment and Post evoked a cardio-protective effect by improving myocardial injury and attenuating fibrosis induced by diabetes. This combined treatment can be recommended as a useful strategy to restore cardio-protection in hearts with diabetic comorbidity.