Cardioprotective Effects Of A New Glutamiс Acid Derivative In Chronic Alcohol Intoxication

Abstract Alcohol abuse is a risk factor for heart damage and deterioration of its inotropic function. Currently, there is no pathogenetic pharmacological treatment for alcohol-induced myocardial injury. Therefore, the study of drugs with cardioprotective action is of current interest. Our earlier studies of stress-induced heart damage showed that a new derivative of glutamic acid - glufimet protects the myocardium's inotropic function and limits lipid peroxidation. Also, we found that it increases the activity of antioxidant enzymes and improves mitochondrial respiration. The purpose of our study was to assess the effect of glufimet on the heart after chronic alcohol intoxication (CAI). The comparison drug was mildronate, possessing cardioprotective properties, and treating alcohol withdrawal. We conducted our study on the female Wistar rats (10 months, 280-320 g). CAI was simulated by replacing drinking water with a 10% ethanol solution sweetened with sucrose (50 g/l) within 24 weeks. The day after the animals stopped ethanol solution drinking, the control group were injected intraperitoneally with a saline solution once a day for 14 days, while the experimental groups received glufimet (28.7 mg/kg), and the drug of comparison mildronate (50 mg/kg), respectively. After that, we studied the heart contractility with volume load, adrenergic reactivity, and maximum isometric load tests. Under CAI, the control group showed significantly lower growth in the left ventricular pressure (LVP), myocardium contraction rate, and relaxation rate during functional tests. A higher concentration of LPO products (malondialdehyde) and low activity of antioxidant enzymes (superoxide dismutase, glutathione peroxidase), disturbance the mitochondrial respiration compared to the control group, were registered. While being treated with glufimet and mildronate, the animals demonstrated higher growth rates of myocardial contraction and relaxation, LVP, compared to the control group. Mitochondrial functioning and activity of the antioxidant enzymes increase in the same group as well.