A high fructose diet (HFD) and advanced age are key factors for the gradual loss of physiological integrity of adipose tissue. Endogenous hydrogen sulfide (H2S) has beneficial effects on cytoprotection and redox balance. But its interactive effects on age-related damage of mesenteric vessels and connective and adipose tissues (MA) during HFD which could be the base of the development of effective physiological-based therapeutic strategy are unknown. The aim of study was to investigate age- and HFD-induced mesenteric cellular changes and activities of enzymes in H2S synthesis and to test the effects of sodium hydrosulfide (NaHS) which is considered an H2S donor on them. Adult and aged male rats on a standard diet (SD) or 4-week HFD were exposed to acute water-immersion restraint stress (WIRS) for evaluation of mesenteric subcellular and cellular adaptive responses by electron microscopy. The effects of exogenous NaHS (5.6 mg/kg/day for 9 days) versus vehicle on mesentery changes were investigated. Serum glucose level, thiobarbituric acid reactive substances (TBARS), and activities of cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS), thiosulfate-dithiol sulfurtransferase (TST), and sulfite oxidase (SO) were examined by spectrophotometry. In both adult and aged SD groups, treatment with NaHS protected mesenteric cells after WIRS. In both groups, the treatment with NaHS also protected MA mitochondria, microvascular endothelial and sub-endothelial structures, and fibroblasts versus the vehicle-treated group that had signs of damage. HFD increased MA injury and mitochondrial changes in both aged and adult rats. HFD-associated malfunction is characterized by low activities of CSE, CBS, TST, SO, and increased TBARS. Finally, we demonstrated that pretreatment with NaHS inhibited MA and mitochondria alterations in aged rats exposed to HFD and WIRS, lowered TBARS, and enhanced H2S enzyme activities in contrast to the vehicle-treated group. Mitochondrial integrity alterations, endothelial damage, and redox imbalance are key factors for rat mesenteric adipose tissue damage during advanced age. These alterations and MA hypertrophic changes retain the central for HFD-induced damage. Moreover, H2S signaling contributes to MA and mitochondria redox balance that is crucial for advanced age and HFD injury. The future study of H2S donors’ effects on mesenteric cells is fundamental to define novel therapeutic strategies against metabolic changes.

Introduction.The mesentery is one of the recently described separate organs, whose functions and ability to protect itself from injuries are still unclear. Adipocytes are a part of the mesentery (MAC); however, little is known about their age-related changes, responses at times of damage induced by hyperglycemia, stress, and their interaction. Hydrogen Sulfi de (H 2 S) system is a key endogenous cytoprotective system that operates by catalytic activities of Cystathionine-γ-lyase (CSE), Cystathionine-β-synthase (CBS), and Sulfi te Oxidase (SUOX) but their role in adipocyte cytoprotection is still unknown.Aim. To evaluate the CBS, CSE, SUOX activities in the mesenterium and ultrastructural changes of MAC in aged rats fed with HSD, under conditions of stress, their combination, and modifi cation of H 2 S synthesis: by injecting NaHS and hybrid nonsteroid anti-infl ammatory drug, which is rich in H 2 S-acetylsalicylic acid (H 2 S-ASA).Material and Methods. The research was conducted on old rats, divided into the control group (animals were on the standard diet and received 1.0 ml of 0.9% NaCl solution per os); accordingly, the remaining animals with HSD in per os groups received 2) 1.0 ml of 0,9% NaCl solution; 3) NaHS at a dose of 100 mcM/kg/day, 9 days; 4) 1.0 ml of 0.9% NaCl solution, 9 days, and stress induction (Takagi, K, 1964); 5) NaHS at a dose of 100 mcM/kg, 9 days, and stress induction; 6) ASA in the dose of 10 mg/kg/day, 9 days, NaHS at a dose of 100 mcM/kg, and stress induction; 7) ASA, 10 mg/kg/day, 9 days, and stress induction; 8) H2S-aspirin (H2S-ASA, ATB-340), 17.5 mg/kg/day, 9 days, and stress induction. Subcellular modifi cations of adipocytes were researched using the transmission electronic microscopy (TEM). CSE, CBS, SUOX enzyme activity was assessed using the standard biochemical methods. (р <0,05). Using the aspirin along with NaHS led to the 67% increase in H 2 S/CSE і H 2 S/CBS activity in rats with HSD as compared to the group receiving normal saline. SUOX activity constituted 5.27 nM/min•mg in the control group, 4.05 nM/min×mg in rats with HSD; in the groups of HSD with NaHS and stress, the obtained values were approximately equal to control values Conclusions. This study confi rms the important role of CSE/H2S pathway in the life of mesenteric adipocytes and its cytoprotective effect. The high activity of the expression of CSE and КОРОТКІ ПОВІДОМЛЕННЯ BRIEF COMMUNICATION Праці НТШ Медичні науки 2018, Том 54, № 2 NTSN MS 2018, Vol. 54, 2 Короткі повідомлення Brief communication SUOX pathways in case of H2S synthesis in mesenteric adipocytes and disorders caused by age and hyperglycemia may be related to the development of non-specifi c infl ammation and potentially used to treat obesity. H2S-aspirin may become an effective drug for prevention of age-related infl ammation and may have a protective effect in case of hyperglycemia. Disclosures. No confl icts of interest, fi nancial or otherwise, are declared by the authors. Author contribution. Oleh Revenko drafted manuscript; Natalia Zaichko ...

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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 (H 2 S) 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 h 2 S 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 Н 2 S-releasing aspirin (aSa) derivative (h 2 S-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 vehicletreated group that had signs of endothelial dysfunction, aM damage and dysfunctional mitochondria. The effect of H 2 S-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. H 2 S 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 h 2 S could lead to a novel approach for anti-obesity treatment. K e y w o r d s: hydrogen sulfide (H 2 S), thiobarbituric acid reactive substances (TBaRS), cystathionine gamma-lyase (CSE), cystathionine beta-synthase (CBS), oxidative stress, adipocytes, mesentery, mitochondria.

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