Changes in the respiratory function of the heart and brain mitochondria of animals after chronic alcohol intoxication affected by a new GABA derivative

Abstract

Introduction: Chronic ethanol consumption leads to significant functional and structural changes in the mitochondria of the heart and brain, increasing generation of reactive oxygen species. Therefore, the search for substances, which improve the functional state of the mitochondria and, meantime, reduce the oxidative stress, is relevant. Materials and methods: 10-months-old Wistar female rats were used in the experiments. Chronic alcohol intoxication (CAI) was modelled by replacing drinking water with a 10% ethanol solution containing sucrose (50 g/L) for 24 weeks. Four groups were formed: 1 – intact animals; 2 – animals after chronic alcohol consumption; 3 – rats after CAI which were administered RSPU-260 (25 mg/kg); 4 – rats after CAI which were administered the reference drug Mildronate (50 mg/kg). The intensity of lipid peroxidation (LPO) and the rate of oxygen consumption in various metabolic states were determined. Results and discussion: Administration of the compound RSPU-260 to the animals exposed to alcohol over a long period of time resulted in an increase in both the rate of oxygen consumption (state 3) and the respiratory control ratio (RCR) of the mitochondria of heart and brain cells. The use of a GABA derivative promoted a decrease in malonic dialdehyde in the mitochondria of the heart and brain. Total SOD activity in the mitochondria of heart cells was significantly increased in the groups of rats treated with RSPU-260. In terms of efficiency, the compound RSPU-260 was comparable to the reference drug Mildronate. Conclusions: The compound RSPU-260, and the reference drug Mildronate improve mitochondrial oxidative phosphorylation in heart and brain cells, the functioning of antioxidant enzymes in animals after CAI, and can be used to correct alcoholic damage to these organs.