Ukr.Biochem.J. 2020; Volume 92, Issue 2, Mar-Apr, pp. 86-97


Exogenous hydrogen sulfide for the treatment of mesenteric damage associated with fructose-induced malfunctions via inhibition of oxidative stress

O. Revenko1*, N. Zaichko2, J. Wallace3, O. Zayachkivska1

1Department of Physiology, Danylo Halytskyy Lviv National Medical University, Ukraine;
2Department of Biochemistry and General Chemistry,
National Pirogov Memorial Medical University, Vinnytsia, Ukraine;
3Department of Physiology and Pharmacology, University of Calgary, Canada;

Received: 30 December 2019; Accepted: 27 March 2020

Remodeling of adipocytes in mesentery (AM) associated with nutritional overload from high fructose diet (HFD) is a source of several comorbidities. However, its pathogenesis is still unclear and there are no specific effective drugs for AM remodeling. Recently hydrogen sulfide (H2S) demonstrated potent cytoprotective actions. The purpose of this study was to investigate the effects and underlying mechanisms of AM remodeling in rats fed HFD and with H2S pre-treatment. Adult male rats on standard diet (SD, control group) or HFD that underwent acute water-immersion restraint stress (WIS) were evaluated for subcellular AM adaptive responses by electron microscopy. The effects on AM of exogenous sodium hydrosulfide (NaHS, 5.6 mg/kg/day for 9 days) and the Н2S-releasing aspirin (ASA) derivative (H2S-ASA [ATB-340], 17.5 mg/kg/day) vs conventional ASA (10 mg/kg/day) vs vehicle were investigated. Serum glucose level, thiobarbituric acid reactive substances (TBARS), and activities of cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS) were examined biochemically using spectrophotometry. In the HFD groups, treatment with NaHS protected AM, as mesenteric microvascular endothelial and sub-endothelial structures were observed vs the vehicle-treated group that had signs of endothelial dysfunction, AM damage and dysfunctional mitochondria. The effect of H2S-ASA was characterized by protection of AM against HFD and WIS-induced injury, with lower TBARS blood level and increased CSE and CBS activities. Carbohydrate overload for 4 weeks is sufficient to cause AM oxidative damage, mitochondrial dysfunction and endothelial changes. H2S plays an important role in mesenteric adipocyte cellular survival against HFD-induced oxidative stress by decreasing overproduction of TBARS and mitochondrial dysfunction. The use of H2S could lead to a novel approach for anti-obesity treatment.

Keywords: , , , , , , ,


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