Blazhchenko V. Participation of the hydrogen sulfide system in the mechanisms of development of renal dysfunction in experimental obesity. – Qualified scientific work on the rights of the manuscript

Українська версія

Thesis for the degree of Doctor of Philosophy (PhD)

State registration number

0822U101049

Applicant for

Specialization

  • 091 - Біологія. Біологія

22-12-2022

Specialized Academic Board

ДФ 05.600.059

Vinnytsia National Pirogov Memorial Medical University

Essay

In-depth scientific ideas about the participation of the H2S system in the mechanisms of renal dysfunction under conditions of alimentary obesity. It has been established that long-term use of a high-calorie, high-fat diet initiates the formation of H2S deficiency in the kidneys; decrease in H2S-producing activity of the transsulfuration enzymes (cystathionine-gamma-lyase, cystathionine-β-synthase); suppression of the activity of cysteine aminotransferase / 3-mercaptopyruvate sulfur transferase, and the thiosulfate-dependent pathway of H2S metabolism. A comprehensive assessment of the effect of metabolic correctors (cofactors and metabolites of sulfur-containing amino acid metabolism) – zinc sulfate, lipoic acid, sodium thiosulfate and taurine – on H2S metabolism and associated processes in the kidneys of rats under conditions of diet-induced obesity (DIO). It is proven that all metabolic correctors reduce disorders of H2S exchange in the kidneys of rats with DIO, while zinc sulfate and lipoic acid more effectively correct the activity of the transsulfuration enzymes and thioredoxin reductase, increase the renal expression of CSE, CBS genes, sodium thiosulfate more effectively increases the activity of thiosulfate (thiol) sulfur transferases and sulfite oxidases, and taurine has a moderate effect on H2S production. Based on the results of the evaluation of biochemical markers of inflammation and fibrogenesis (IGF-1, TNF-alpha), the morphological state of the kidneys and functional markers of renal dysfunction, it was shown that zinc sulfate and lipoic acid provided the most pronounced nephroprotective effect among the modulators of H2S exchange under DIO conditions, while sodium thiosulfate and taurine had a moderate effect. New ways of increasing the adaptive reserves of the kidneys under conditions of DIO based on the modulation of the transsulfuration and thiosulfate sulfurtransferase pathways of H2S exchange were experimentally substantiated.

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