HYDROGEN SULFIDE SYSTEM ATTENUATES INJURY BY HYPERGLYCEMIA AND STRESS: ROLE OF MESENTERIC ADIPOCYTES IN AGED ANIMALS

Abstract

Introduction. The mesentery is one of recently described separate organs which functions and its ability to protect injury are still unclear. Adipocytes are a part of mesentery (MAC), however, it is a little known about their age-related changes, reactive response during damage induced by hyperglycemia, stress, and their interaction. Hydrogen Sulfide (H2S) system is key endogenous cytoprotectvite system that operated by catalytic activities of Cystathionine-γ-lyase (CSE), Cystathionine-β-synthase (CBS), and Sulfite Oxidase (SUOX) but their role in adipocyte cytoprotection are still unknown.

Aim. To evaluate the CBS, CSE, SUOX activities in the mesenterium and ultrastructural changes of MAC in aged rats fed with HSD, at stress induction, and modification of H2S synthesis by NaHS and hybrid nonsteroid anti-inflammatory drugs H2S-acytylsalicylic acid (H2S-ASA).

Material and Methods: All experiments were carried out on the aged rats which divided to the control group (standard diet) and experimental groups (28-days hypercaloric high-carbohydrate diet, as HSD by V. Kozar, 2008) without and with acute stress by water-immobilization stress model by Takagi, 1964, and pretreated per os by: 1) control group by vehicle (1,0 ml of saline), rats from 2-8 groups with HSD for 2) 1,0 ml of saline; 3) NaHS in a dose of 100 мkmol/kg, 9 days; 4) 1,0 ml of saline and induction of stress; 5) NaHS at a dose of 100 мkmol/kg and induction of stress; 6) ASA at a dose of 10 mg/kg/day for 9 days, NaHS at a dose of 100 мkmol/kg, and induction of stress; 7) ASA,10 mg/kg/day, per 9 days; 8) H2S-ASA ( ATB-340), 17,5 mg/kg/day, per 9 days). Subcellular changes of MAC were detected by transmission electron microscopy (TEM). MAC CSE, CBS, SUOX activities were evaluated by standard biochemical methods.

Results. In HSD group with NaHS endothelial and sub-endothelial structures destructions were absent, the nucleus of endothelial cells it was observed an uneven condensation of chromatin. Effect of hybrid H2S-ASA characterized as a protective action and MAC “slimming”. The use of H2S-ASA showed an increase on 15% of the general activity of H2S/CSE and H2S/CBS vs ASA pretreatment (p<0.05). The use of aspirin and NaHS has shown an increase on 67% H2S/CSE and H2S/CBS activities in HSD rats vs saline group. SUOX activity was 5.27 nmol/min•mg in control, HSD rats – 4.05 nmol/min•mg; with NaHS HSD and stress were approximately same as control.

Conclusions: This study suggests an important role for CSE/H2S pathway in the mesenteric adipocyte cellar survival and control cytoprotection. High expression activities in CSE/H2S and SUOX pathways in mesenteric adipocytes compromised by age, hyperglycemia might be associated with the development of low-grade inflammation and may be a potential therapeutic target for obesity treatment. H2S-ASA could be an effective tool for prevention of age-related inflammation and exert defensive effect against hyperglycemia.