Role of monoamine oxidases to oxidative modification of myocardial proteins in rats with alloxan diabetes

Résumé fourni par la source

Diabetes mellitus is associated with a high risk of developing coronary heart disease, cardiac autonomic neuropathy, and diabetic cardiomyopathy, all of which involve oxidative stress mediated by insulin deficiency. The contribution of monoamine oxidases (MAOs) to the development of diabetic cardiomyopathy is currently being intensively studied, and enzyme inhibitors are considered promising cardioprotective drugs for diabetes. However, the possible contribution of MAO-A and MAO-B to direct oxidative damage to proteins and lipids in the myocardium during prolonged hyperglycemia remains unclear. The aim of the study was to assess the role of MAOs in the development of oxidative damage to myocardial proteins in alloxan diabetes. Material and Methods. The study was performed on 54 mature Wistar rats of both sexes. Diabetes mellitus was modeled by intraperitoneal administration of alloxan monohydrate at a dose of 163 mg/kg. To assess the contribution of MAOs to the development of oxidative stress, the MAO-B inhibitor selegiline was administered subcutaneously at a dose of 5 mg/kg daily. On the fourteenth day after alloxan administration, biomaterial for research was obtained. Oxidative modification of proteins in myocardial homogenates was determined spectrophotometrically by reaction with 2,4-dinitrophenylhydrazine, levels of lipid peroxidation products ‒ by extraction-spectrophotometric methods, MAO activity ‒ spectrophotometrically. Results and discussions. Within fourteen days of alloxan administration, an increase in glycemia was observed, accompanied by activation of MAO-A and MAO-B, as well as the accumulation of free radical protein and lipid oxidation products in the myocardium. Administration of selegiline to animals receiving alloxan prevented the activation of MAOs and the accumulation of protein oxidative modification products. These results demonstrate the potential for a direct prooxidant effect of MAOs in the myocardium and support the potential of research aimed at developing approaches that utilize drugs that modulate MAO activity in diabetes.

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