EFFECT OF TYPE-2 DIABETES MELLITUS ON THE HEART OF ADULT ALBINO RAT AND THE POSSIBLE PROTECTIVE ROLE OF BROMOCRIPTINE: ULTRASTRUCTURAL AND IMMUNOHISTOCHEMICAL STUDY
Gamal Hosny Mohamed, Mohamed Hafez Shaaban
Department of Anatomy and Embryology, Faculty of Medicine, Cairo University
Background: The type 2 diabetes mellitus accounts for 90 to 95% of diabetic patients. It has become one of the major causes of premature illness and death, mainly due to the increased risk of cardiovascular complications which are responsible for up to 80% of deaths. Bromocriptine mesylate, a dopamine 2 agonist, is approved for the treatment of type 2 diabetes mellitus by US-FDA in 2009. However, its efficacy to reduce cardiovascular complications associated with type 2 diabetes mellitus are yet to be explored fully.
Aim of the Work: The objective of the present study was to evaluate the effect of Bromocriptine on cardiac complications associated with type-2 diabetes mellitus.
Material and Methods: The present study was carried out on forty adult male albino rats. Their average weight was 200 grams. They were divided into four equal groups. Group I (control group) received daily intraperitoneal injection 0.5% carboxy methyl cellulose in distilled water for 6 weeks. Group II received a daily intraperitoneal injection of 10 mg/kg Bromocriptine for 6 weeks. Group III received a daily oral dose of fructose 66% for 6 weeks to induce type 2 diabetes mellitus. Group IV received a daily oral dose of fructose 66% for 6 weeks to induce type 2 diabetes mellitus then followed by a daily intraperitoneal injection of 10 mg/kg Bromocriptine for a period of 6 weeks. At the end of the experiment, the rats from each group were weighed and sacrificed. Heart specimens were taken and processed for histological, electron microscopical and immunohistochemical studies.
Results: Fructose-fed rats (group III) showed significant weight gain. Light microscopic studies revealed many degenerative changes varying from vacuolation to myocytolysis and loss of myofibrils. Evidences of apoptosis were detected in the form of cytoplasmic eosinophilia and the nuclei varying from peripheral margination of chromatin up to pyknosis, confirmed immunohistochemcally with positive reaction for caspase-3 activity that was increased up to four times of the control level as detected by image analysis Ultrastructural examination showed extensive degeneration of the muscle fibers with marked loss and even complete disappearance of myofibrils, there was dilatation of smooth endoplasmic reticulum, increased amount of glycogen granules and mitochondriosis, with degeneration and moth-eaten appearance of many mitochondria. The nucleus appeared hyperchromatic with peripherally clumped chromatin. The above mentioned toxic effects on the myocardium were markedly attenuated by Bromocriptine administration. Administration of Bromocriptine showed significant decrease in weight gain, protection from hypertrophy and degenerative changes in myocardium.
Conclusion: Bromocriptine has beneficial effect in reduction of cardiac complications associated with type 2 diabetes mellitus.