Роль системи Н2S / цистатіонін-γ-ліаза в механізмах кардіопротекторної дії вітаміну D за дієт-індукованого ожиріння

Abstract

Obesity and vitamin D deficiency are risk factors for cardiovascular disease that are often coexisting. The identification of new biochemical factors that may modify the cardiovascular effects of vitamin D in obesity remains relevant. The aim of study: to estimate the role of the H 2 S / cystathionine-γ-lyase system in the mechanisms of cardioprotective effect of vitamin D in diet-induced obesity. Methods. The experiments were carried out on 40 white male laboratory rats in accordance with the principles of bioethics (Directive 2010/63/EU). The active form of vitamin D – 1,25(OH) 2 D 3 was administered to animals with a model of diet-induced obesity (DIO) for 2 weeks. Propargylglycine and NaHS were used to modulate the state of the H 2 S / cystathionine-γ-lyase system. Levels of H 2 S, caspase-3, TNFα, HSP60, HSP70, and oxidative stress markers were determined in myocardial and thoracic aortic homogenates. Results. The administration of 1,25(OH)D 3 reduced biochemical disorders in myocardium and aorta in DIO: H 2 S content and cystathionine-γ-lyase activity increased, levels of inflammatory and apoptotic mediators (caspase-3, TNFα) decreased, HSP60 and HSP70 levels normalized, and signs of oxidative stress decreased. The cardioprotective effects of 1,25(OH)D 3 were significantly reduced by inhibition of H 2 S synthesis, while the H 2 S donor (NaHS) enhanced these effects. Conclusions. In obesity, modulation of H 2 S / cystathionine-γ-lyase activity affects the cardioprotective effects of vitamin D, which are realized through the signaling pathways of inflammation, apoptosis and oxidative stress.