Gender-related features of liver mitochondrial dysfunction in the development of metabolic syndrome and its pharmacological correction

Abstract

The liver as a central organ of metabolism regulates homeostasis of carbohydrates, proteins and lipids. At the same time, key organelles of any cell are mitochondria including liver cells as well. Mitochondria play a crucial role in the cellular energy metabolism. Their main function is generation of adenosine triphosphate mainly by means of oxidative phosphorylation providing a continuous supply of energy to various vital cellular processes. Therefore, the objective of our research was the study of gender differences in liver mitochondrial dysfunction with metabolic syndrome development and possibility of its pharmacological correction by means of carbacetam. The experiments were carried out on laboratory nonlinear white male and female rats with the body weight of 0.220–0.250 kg. Metabolic syndrome was simulated by keeping the rats on high fat diet and free access to fructose solution (100 g/L). Carbacetam was administered intraperitoneally in a dose of 5 mg/kg during 14 days. Therefore, the results of our research are indicative of the development of mitochondrial dysfunction in the liver cells of rats of different genders under conditions of simulating metabolic syndrome. Male rats appeared to be more susceptible to damage. At the same time, administration of carbacetam as a modulator of GABA-receptors demonstrated positive changes from the point of view of mitochondrial functioning. These changes include a decreased relative rate of mitochondrial swelling and decreased peroxide oxidation of lipids and proteins with increasing activity of antioxidant defense enzymes.