93 Effect of insulin and captopril on diabetic cardiomyopathy in adult male albino rat: Histological, biochemical and pharmacological study Radwa Mohammed Ahmed 1 , Asmaa Mohammed Mohammed Ibrahim 2 , Mohamed Hussein Elmahdi 3 , Mostafa Yehia Abdelwahed 4 , Ayman Mohamed Helal 5 , Mohamed Mahmoud Sofi 1 1 Anatomy and Embryology Department, Faculty of Medicine, Fayoum University, Egypt 2 Biochemistry and Molecular Biology Department, Faculty of Medicine, Fayoum University, Egypt 3 Pathology Department, Faculty of Medicine, Fayoum University, Egypt 4 Physiology Department, Faculty of Medicine, Fayoum University, Egypt 5 Pharmacology Department, Faculty of Medicine, Fayoum University, Egypt Abstract: Introduction: Diabetic cardiomyopathy is characterized by structural and functional myocardial alterations. hyperglycaemia is a major contributing factor in its pathogenesis. So, insulin therapy is mandatory in diabetic patients. Angiotensin converting enzyme inhibitors (ACEIs) e.g. captopril, may play a beneficial role in management of diabetic cardiomyopathy. However, combined insulin and captopril therapy is much more effective in attenuation of severe cardiac damage exerted by oxygen free radicals released in diabetic patients via different mechanism most probably due to hyperglycaemia. Aim of work: to elucidate the protective role of insulin and captopril on diabetes mellitus induced histological alterations in myocardium of adult male albino rat. Material and methods: This research used 50 adult male albino rats weighing 180-220 g. The rats were classified into five groups 10 rats each: Group I (Normal control): The rats of this group were injected intravenously once with 0.9% saline. Group II (Diabetic Control): The rats of this group were injected once with STZ intravenously into the tail vein on a 40 mg / kg dose. Group III (Insulin-treated Diabetic rats): The rats of this group were injected subcutaneously with insulin once daily at 2 U / kg body weight dose after induction of diabetes mellitus for six weeks. Group IV (Diabetic rats treated with captopril): The rats of this group were administered with captopril by oral gavage at a 100mg / kg body weight dose once daily for six weeks after diabetes mellitus induction Group V (Diabetic rats treated with insulin and captopril): The rats of this group rats received a combined treatment of insulin at a dose of 2U/ kg/day and captopril 100 mg/kg by the same previously mentioned routes. Results: Examination of specimens of diabetic rats revealed markedly disturbed myocardial architecture, mononuclear cell infiltration, cytoplasmic degeneration and extensive fibrosis. Insulin and captopril co-administration markedly ameliorated these histological alterations more than using insulin or captopril alone. [Radwa Mohammed Ahmed, Asmaa Mohammed Mohammed Ibrahim, Mohamed Hussein Elmahdi, Mostafa Yehia Abdelwahed, Ayman Mohamed Helal, Mohamed Mahmoud Sofi. Effect of insulin and captopril on diabetic cardiomyopathy in adult male albino rat: Histological, biochemical and pharmacological study. J Am Sci 2020;16(8):93-109]. ISSN 1545-1003 (print); ISSN 2375-7264 (online). http://www.jofamericanscience.org . 10. doi:10.7537/marsjas160820.10 . Key words: Diabetic cardiomyopathy, insulin, captopril, heart. 1. Introduction: Diabetes mellitus a major health problem associated with cardiovascular diseases and cardiac mortality. Diabetic cardiomyopathy is characterized by structural and functional myocardial alterations; myocardial apoptosis and fibrosis mainly due to oxidative stress and DNA damage. The myocardium is very sensitive to damaging effect of reactive oxygen species (ROS) because of its highly oxidative metabolism and deficient antioxidant defence mechanisms (Westermann et al, 2009; Falcoa-Pires et al, 2012 and Zheng et al, 2019). Singh et al, 2008 reported that insulin therapy is mandatory in diabetic patients especially those who developed diabetic cardiomyopathy in order to reduce blood glucose level. They added that hyperglycaemia is a major contributing factor in the pathogenesis of diabetic cardiomyopathy and release of ROS in myocardial tissue. Angiotensin converting enzyme inhibitors (ACEIs) are widely used for cardiovascular disease treatment; congestive heart failure, hypertension and myocardial infarction. In diabetic cardiomyopathy, hyperglycemia causes overproduction of the mitochondrial superoxide, which contributes to ROS