STATUS OF THE PROOXIDANT-ANTIOXIDANT SYSTEM AND MORPHOFUNCTIONAL CHANGES IN THE LIVER OF RATS -MALES AND FEMALES WITH METABOLIC SYNDROME AND THEIR CORRECTION BY A GABA RECEPTOR MODULATOR

Metabolic syndrome (MetS) is among the most widespread medical and social problems of our time, combining insulin resistance, abdominal obesity, dyslipidemia, and arterial hypertension, with a population prevalence reaching 25–35% and a further upward trend. The liver plays a leading role in the pathogenesis of MetS, its damage being closely linked to the development of oxidative stress. At the same time, sex-related differences in the course of hepatic metabolic disturbances and the possibilities of their pharmacological correction with GABA-receptor modulators, in particular carbacetam, remain insufficiently studied. Aim of the study — to investigate the state of the prooxidant–antioxidant system and morphofunctional changes in the liver of male and female rats with experimental metabolic syndrome, and to evaluate the efficacy of their correction with the GABA-receptor modulator carbacetam. Materials and methods. The study was carried out on sexually mature outbred white rats of both sexes weighing 220–250 g under vivarium conditions, in compliance with the principles of humane animal treatment. MetS was modeled by keeping the animals for 60 days on a high-calorie, high-fat diet with free access to a 10% fructose solution. The exclusion criterion for animals was a fasting glycemia level below 7.0 mmol/L upon reproduction of the MetS model. Animals with verified syndrome were administered carbacetam (5 mg/kg, intraperitoneally, for 14 days); control and comparison groups received 0.9% NaCl solution according to the same regimen (7 rats per group). In the cytoplasmic fraction of the liver, lipid peroxidation products (TBA-active products) and oxidative protein modification products (OPM370, OPM430) were determined, along with SOD and catalase activity. Morphological assessment was performed on sections stained with hematoxylin-eosin and bromophenol blue according to Mikel Calvo, with determination of the R/B coefficient using computer microspectrophotometry. Statistical processing of results included calculation of the arithmetic mean and its standard error. Results. Reproduction of MetS in rats of both sexes was accompanied by a significant increase in OPM and TBA-active products against a background of decreased catalase activity (and SOD in males), reflecting intensification of free-radical oxidation and depletion of antioxidant defense. In parallel, the proportion of altered hepatocytes and the R/B coefficient in hepatocytes and endotheliocytes increased, indicating accumulation of oxidatively modified protein fractions; in females, these disturbances were more pronounced than in males, indicating sexual dimorphism of hepatic injury in MetS. Two-week administration of carbacetam produced a significant decrease in OPM and TBA-active product levels, partial restoration of catalase activity (and SOD in males), and a reduction in the proportion of altered hepatocytes and the R/B coefficient in both groups, although the studied parameters did not reach control levels. Conclusions. Experimental metabolic syndrome causes marked morphofunctional disturbances of the liver in rats of both sexes, driven by activation of protein oxidative modification and lipid peroxidation processes against a background of suppressed antioxidant enzymes; these changes are more pronounced in females than in males, indicating sexual dimorphism in liver damage. Carbacetam at a dose of 5 mg/kg for 14 days provides partial correction of morphological and biochemical hepatic parameters in rats of both sexes with metabolic syndrome, confirming its hepatoprotective and antioxidant potential and supporting the feasibility of further study of the drug.