THE INFLUENCE OF HYDROGEN SULPHIDE EXCHANGE MODULATORS ON BIOCHEMICAL MECHANISMS OF MYOCARDIAL DAMAGE IN ALCOHOLIC CARDIOMYOPATHY
DOI:
https://doi.org/10.11603/1811-2471.2024.v.i4.14970Keywords:
alcoholic cardiomyopathy, propargylglycine, hydrogen sulfide, heart, inflammation, apoptosis, endothelial dysfunction, oxidative stress, cardiocytolysis, pharmacocorrection, ratsAbstract
Resume. Alcoholic cardiomyopathy is an urgent medical and social problem due to its high prevalence, frequent development of complications and high mortality. Today, the question of the pathogenesis of alcoholic heart damage remains open, which largely hinders the development of effective means of pharmacocorrection.
The aim – to evaluate the effect of hydrogen sulfide exchange modulators (sodium hydrogen sulfide and propargylglycine) on the main pathogenetic links of myocardial damage in experimental alcoholic cardiomyopathy.
Material and Methods. Experimental studies were conducted on 65 Wistar male rats. According to the purpose of the study, all animals were divided into four groups (15–20 rats each): 1st group – control; 2nd group – animals that were simulated alcoholic cardiomyopathy by intragastric administration of 20 % aqueous ethanol solution (at a dose of 8 g/kg/day) for 90 days; groups 3 and 4 after alcoholic cardiomyopathy induction were injected intraperitoneally for two weeks with H2S donor (NaHS – 3 mg/kg/day) and propargylglycine (50 mg/kg/day), respectively. The activity of creatine phosphokinase (CPK) and aspartate aminotransferase (AST) enzymes was determined in blood serum.
In the postnuclear supernatant of the heart homogenate, the content of caspase-3, TNF-α, malondialdehyde (MDA), protein carbonyl groups (CG), the activity of endothelial and inducible isoforms of NO-synthase (NOS), as well as the parameters of H2S metabolism were evaluated: H2S level, the activity of cystathionine-γ-lyase (CGL), cysteine aminotransferase coupled to 3-mercaptopyruvate sulfurtransferase (CAT/3-MST) and the rate of H2S utilization.
Results. NaHS and propargylglycine usage reveals a multi-vector effect on pathochemical processes in the heart with alcoholic cardiomyopathy. Administration of NaHS in alcoholic cardiomyopathy is accompanied by a probable decrease in disturbances of H2S metabolism in the heart (probably increases the level of H2S, activity of CGL, CAT/3-MST by 20 – 31.1 % and reliably decreases the rate of H2S utilization by 37.0 %), decreases inflammation activity, apoptosis, oxidative stress and cytolysis in the heart (the levels of TNF-α, caspase-3, MDA, CG and serum activity of CK and AST are significantly reduced by 20.3 – 59.8 %, p<0.05) and reduces the imbalance of NOS isoforms (iNOS activity probably decreases by 26.1 % and eNOS activity increases by 36.4 %, p<0.05) in comparison with untreated animals. At the same time, the use of propargylglycine increased the scale of pathochemical disorders in the heart of experimental rats induced by long-term alcoholism.
Conclusions. The use of the hydrogen sulfide donor NaHS in alcoholic cardiomyopathy normalizes H2S exchange in the myocardium and is accompanied by anti-inflammatory, antiapoptotic, antioxidant, cytoprotective and endotheliotropic effects in the rats’ heart. Contrary, the introduction of an inhibitor of H2S synthesis caused the opposite changes.
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