Palamarchuk I. The role of the hydrogen sulfide system in the mechanisms of myocardial damage and cardioprotection in experimental diabetes mellitus

Scientific data on the role of H2S system in mechanisms of diabetes-associated myocardial damage were added, and effectiveness of antidiabetic drug metformin in combination with H2S donor was determined. It is showed that streptozotocin-induced diabetes in cardiovascular system forms deficiency of hydrogen sulfide (H2S), decreases activity of H2S-synthesizing enzymes (cystationin-γ-lyase, cysteine aminotransferase), impaires activity of mitochondrial stages of H2S metabolism with participation of sulfite oxidase and thioredoxin reductase, CSE gene expression is reduced. Administration of cystathionine γ-lyase inhibitor propargylglycine exacerbates diabetes-associated biochemical changes in myocardium and aorta: deepens signs of H2S deficiency, oxidative stress, thiol-disulfide imbalance; increases serum and myocardial expression of galectin-3; increases cytometric signs of cells’ proliferative activity and DNA fragmentation in myocardium; exacerbates disorders of H2S-dependent vasodilation in rats with streptozotocin-induced diabetes. Administration of H2S - sodium hydrogen sulfide (NaHS) prevents the development of these biochemical disorders in myocardium (prevents decrease in H2S, increases activity of cystathionine-γ-lyase and CSE gene expression, reduces thiol-disulfide disorders), reduces apoptotic activity, increases vasodilation in rats with diabetes. Effect of antidiabetic drug metformin on activity of enzymes of H2S synthesis and utilization in myocardium, expression of CSE gene in myocardium and aorta, serum and myocardial levels of galectin-3 in diabetic rats. Use of metformin in combination with NaHS provides more effective correction of H2S metabolism disorders, ameliorates antioxidant, antifibrogenic and vasoprotective effects. It is justified the feasibility of corrections of H2S metabolism in cardiovascular system in parallel with antidiabetic pharmacotherapy for prevention of cardiovascular dysfunction and cardiomyopathy.