Egypt J. Histol. Vol. 33, No. 1, March, 2010:92 -102 ^sss? (JSSN; mQ _ Q559) Original Article Influence of Alpha-Lipoic Acid on Streptozotocin Induced Diabetic Cardiomyopathy in Adult Male Albino Rats: A Biochemical and Microscopical Study Samar A. Asker, Shireen A. Mazroa and Hala Abdel-Malek Departments of Histology and Clinical Pharmacology, Faculty of Medicine, Mansoura University ABSTRACT Introduction: Cardiovascular disease is responsible for 80% of deaths among diabetic patients. Diabetic patients may suffer from cardiac insult termed 'diabetic cardiomyopathy'. Aim of the Work: Investigation of biochemical structural and ultrastructural changes of the diabetic hearts and effect of supplementation with alpha-lipoic acid (ALA). Materials and Methods: Thirty adult male albino rats were divided into: group I control rats, group II diabetic rats and group III diabetic rats receiving ALA. Diabetes was induced in rats of groups II and III by streptozotocin drug. The animals were sacrificed after 16 weeks. The hearts and sera were prepared for biochemical and microscopical studies. Results: Diabetic (Group-II) animals showed significant increase in levels of serum; glucose, malondialdehyde (MDA), cholesterol and hepatic glucose -6-phosphatase enzyme (G-6-Pase) activity in addition to a significant decrease in tissue glutathione (GSH). Structurally, cardiac muscle fibers appeared swollen with areas devoid of fibers, with collagen deposition among them. Ultrastructurally, diabetic hearts showed poorly organized myofibrils and sarcomeres, disrupted Z lines, dilated sarcoplasmic reticulum, abnormal mitochondria with heterogonous electron dense matrix and disrupted mitochondrial membranes. Some mitochondria showed vacuoles and fusion with each other. The wall of blood vessels was irregular. Secondary lysosomes and myelin bodies in between myofibrils were detected. In diabetic (Group-Ill) animals, ALA partially prevented biochemical, structural and ultrastructural changes. Conclusion: Different structural, ultrastructural and biochemical changes were evident in diabetic rats after 16 weeks. The supplementation of ALA in diabetic rats partially prevented such changes, suggesting its possible protective effect against the risk of the progression of cardiovascular diseases during diabetes. Corresponding Author: Samar A. Asker Tel.: 0101159990 E-mail: sanaasker@yahoo.com multi-factorial 6,7 . The most important mechanisms of diabetic cardiomyopathy are metabolic disturbances as depletion of glucose transporter, increased free fatty acids, carnitine deficiency and changes in calcium homeostasis 8 ' 9 . The link between hyperglycemia and the development of diabetic cardiomyopathy involves the accumulation of advanced glycated end products (AGEs) within the cells. Advanced glycated end products and their precursors modify macromolecules; producing irreversible cross-links between extracellular matrix proteins 10 ' 11 compromising tissue compliance and causing myocardial stiffness 12 . Lipoic acid (LA) and its reduced form dihydrolipoic acid are present in all prokaryotic and eukaryotic cells and considered a vitamin, but now it is commonly accepted that it can be synthesized de novo in human cells. Lipoic acid is involved in the regulation of carbohydrate and lipid 10(1175-2010) ~" = _ ~ — — — 92 Key Words: Diabetic cardiomyopathy, Alpha-lipoic acid, ALA, structure, ultrastructural, biochemical. INTRODUCTION Cardiovascular disease is responsible for 80% of deaths among diabetic patients 1 . There is an increasing recognition that diabetic patients suffer from a cardiac insult termed 'diabetic cardiomyopathy'. Diabetic cardiomyopathy can progress toward overt heart failure with increased mortality 2 . Diabetic cardiomyopathy can be defined as myocardial disease in patients with diabetes that cannot be attributed to any other known cardiovascular diseases, such as hypertension or coronary artery diseases 3 . It is characterized by both systolic and diastolic dysfunction and caused by a metabolic disorder of the myocardium 4 . However, the mechanisms by which hyperglycemia or associated metabolic abnormalities lead to cardiomyopathy are not fully known. Appropriate approaches to minimize these risks are still being explored 5 . The pathophisiology of diabetic cardiomyopathy is