The effect of hydrogen sulfide metabolism modulators on CSE gene expression, levels of proinflammatory and profibrotic mediators, morphological changes in cardiovascular system of rats in experimental obesity

Abstract

Hydrogen sulfide (H 2 S) is considered to be a multifunctional mediator. Disorders of H 2 S synthesis are related to the pathogenesis of cardio- vascular pathology. Approaches to H2 S metabolism correction in cardiovascular system in obesity are not defined. The aim of study: to estimate the effect of H 2 S metabolism modulators on CSE gene expression, levels of proinflammatory and profibrotic mediators, morphological changes in cardiovascular system of rats in experimental obe- sity (EO). Methods. The experiments were carried out on 70 white non-linear male rats. The care and use of laboratory animals were approved by the general principles of bioethics (Strasbourg, 1986). EO was induced by a high-calorie diet application during 10 weeks. The 8-10-th weeks of the experiment was the period when H 2 S metabolism modulators were administered. The expression of CSE gene, levels of visfatin, TNFα, endothelin-1 and morphological changes were estimated in cardiovascular system. Results. EO results in CSE gene oppression in myocardium and aorta, therewith elevation of visfatin and TNFα levels in myocardium occurs, serum level of endothelin-1 increases, morphological features of cardiomyopathy re- veal furthermore. H 2 S donor (NaHS) and cofactors (α-lipoic acid, zinc sulfate) upregulate CSE gene expression, perform an adjusting effect on biochemical disturbances, reduce signs of cardiomyopathy, while propargylglycine (cysta- thionine-γ-lyase inhibitor) induces the opposite effects. Conclusions. H 2 S is involved in regulation of inflammatory and fibrogenic mediators in cardiovascular system in obesity. Cofactors of H 2 S metabolism effectively correct cardiometabolic disorders in this condition