HYDROGEN SULFIDE SYSTEM ATTENUATES INJURY BY HYPERGLYCEMIA AND STRESS: ROLE OF MESENTERIC ADIPOCYTES IN AGED ANIMALS
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.
Andrew MS, Huffman DM, Rodriguez-Ayala E, Williams NN, Peterson RM, Bastarrachea RA. Mesenteric visceral lipectomy using tissue liquefaction technology reverses insulin resistance and causes weight loss in baboons. Surgery for Obesity and Related Diseases. 2018 14 (6): 833-841. https://doi.org/10.1016/j.soard.2018.03.004
Augsburger F, Szabo C. Potential role of the 3-mercaptopyruvate sulfurtransferase (3-MST)-hydrogen sulfide (H2S) pathway in cancer cells. Pharmacological Research. 2018 Nov 27. https://doi.org/10.1016/j.phrs.2018.11.034
Banerjee R, Chiku T, Kabil O, Libiad M, Motl N, Yadav PK. Assay methods for H2S biogenesis and catabolism enzymes. In Methods in enzymology Academic Press. 2015 Jan 1 (Vol. 554, pp. 189-200).
Beatty JK, Akierman SV, Motta JP, Muise S, Workentine ML, Harrison JJ, Bhargava A, Beck PL, Rioux KP, McKnight GW, Wallace JL. Giardia duodenalis induces pathogenic dysbiosis of human intestinal microbiota biofilms. International journal for parasitology. 2017 May 1;47(6):311-26
Bezpalko L, Gavrilyuk O, Zayachkivska O. Inflammatory response in visceral fat tissue and liver is prenatally programmed: experimental research. J Physiol Pharmacol. 2015 Feb 1;66(66):57-64.
Calderone V, Martelli A, Testai L, Citi V, Breschi MC. Using hydrogen sulfide to design and develop drugs. Expert opinion on drug discovery. 2016 Feb 1;11(2):163-75.
Cheng Y, Ndisang JF, Tang G, Cao K, Wang R. Hydrogen sulfide induced relaxation of resistance mesenteric artery beds of rats. American Journal of Physiology-Heart and Circulatory Physiology. 2017 Nov 10.
Coffey JC, O’Leary DP. The mesentery: structure, function, and role in disease. The Lancet Gastroenterology & Hepatology. 2016 Nov 1;1(3):238-47.
Gagliano-Jucá T, Moreno RA, Zaminelli T, Napolitano M, Magalhães AF, Carvalhaes A, Trevisan MS, Wallace JL, De Nucci G. Rebamipide does not protect against naproxen-induced gastric damage: a randomized double-blind controlled trial. BMC gastroenterology. 2016 Dec;16(1):58.
Gugliandolo E, Fusco R, D’Amico R, Militi A, Oteri G, Wallace JL, Di Paola R, Cuzzocrea S. Anti-inflammatory effect of ATB-352, a H2S− releasing ketoprofen derivative, on lipopolysaccharide-induced periodontitis in rats. Pharmacological research. 2018 Jun 1;132:220-31.
Ianaro A, Cirino G, Wallace JL. Hydrogen sulfide-releasing anti-inflammatory drugs for chemoprevention and treatment of cancer. Pharmacological research. 2016 Sep 1;111:652-8.
Jenkins TA, Nguyen JC, Hart JL. Decreased vascular H2S production is associated with vascular oxidative stress in rats fed a high-fat western diet. Naunyn-Schmiedeberg’s archives of pharmacology. 2016 Jul 1;389(7):783-90.
Kimura Y, Shibuya N, Kimura H. Sulfite protects neurons from oxidative stress. British journal of pharmacology. 2018 May 29.
Kolluru GK, Shen X, Bir SC, Kevil CG. Hydrogen sulfide chemical biology: pathophysiological roles and detection. Nitric oxide. 2013 Nov 30;35:5-20.
Kozar VV, Kudria MY, Ustenko NV, Pavlenko TO, Zhurakovska MV. The state of the humoral component of immunity under conditions of metabolic syndrome with underlying hypoestrogenia and its farmacological correction. Buk Med Herald. 2009;13:141-4.
Li M, Xu C, Shi J, Ding J, Wan X, Chen D, Gao J, Li C, Zhang J, Lin Y, Tu Z. Fatty acids promote fatty liver disease via the dysregulation of 3-mercaptopyruvate sulfurtransferase/hydrogen sulfide pathway. Gut. 2018 Dec 1;67(12):2169-80.
Lucetti LT, Silva RO, Santana AP, de Melo Tavares B, Vale ML, Soares PM, de Lima Júnior FJ, Magalhães PJ, de Queiroz Cunha F, de Albuquerque Ribeiro R, Medeiros JV. Nitric oxide and hydrogen sulfide interact when modulating gastric physiological functions in rodents. Digestive diseases and sciences. 2017 Jan 1;62(1):93-104.
Martinez KB, Leone V, Chang EB. Western diets, gut dysbiosis, and metabolic diseases: Are they linked? Gut microbes. 2017 Mar 4;8(2):130-42.
Mistry RK, Brewer AC. Redox-dependent regulation of sulfur metabolism in biomolecules: implications for cardiovascular health. Antioxidants & redox signaling. 2017; Jul 28. https://doi.org/10.1089/ars.2017.7224
Prieto-Lloret J., Aaronson P.I. Potentiation of Hypoxic Pulmonary Vasoconstriction by Hydrogen Sulfide Precursors 3-Mercaptopyruvate and D-Cysteine Is Blocked by the Cystathionine γ Lyase Inhibitor Propargylglycine. In: Peers C., Kumar P., Wyatt C., Gauda E., Nurse C., Prabhakar N. (eds) Arterial Chemoreceptors in Physiology and Pathophysiology. Advances in Experimental Medicine and Biology. 2015; 860. Springer, Cham
Takagi K, Kasuya Y, Watanabe K. Studies on the drugs for peptic ulcer. a reliable method for producing stress ulcer in rats. Chemical and Pharmaceutical Bulletin. 1964 Apr 25;12(4):465-72.
Takagi K, Okabe S. The effects of drugs on the production and recovery processes of the stress ulcer. Jpn J Pharmacol 1968; 19: 9-19.
Untereiner A, Wu L. Hydrogen sulfide and glucose homeostasis: a tale of sweet and the stink. Antioxidants & redox signaling. 2018 Jun 1;28(16):1463-82.
Wallace JL, Blackler RW, Chan MV, Da Silva GJ, Elsheikh W, Flannigan KL, Gamaniek I, Manko A, Wang L, Motta JP, Buret AG. Anti-inflammatory and cytoprotective actions of hydrogen sulfide: translation to therapeutics. Antioxidants & redox signaling. 2015 Feb 10;22(5):398-410.
Wallace JL, de Nucci G, Sulaieva O. Toward more GI-friendly anti-inflammatory medications. Current treatment options in gastroenterology. 2015 Dec 1;13(4):377-85.
Wallace JL, Motta JP, Buret AG. Hydrogen sulfide: an agent of stability at the microbiome-mucosa interface. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2017 Oct 12;314(2):G143-9.
Wang ZJ, Wu J, Guo W, Zhu YZ. Atherosclerosis and the Hydrogen Sulfide Signaling Pathway–Therapeutic Approaches to Disease Prevention. Cellular Physiology and Biochemistry. 2017;42(3):859-75.
Yang G, Ju Y, Fu M, Zhang Y, Pei Y, Racine M, Baath S, Merritt TJ, Wang R, Wu L. Cystathionine gamma-lyase/hydrogen sulfide system is essential for adipogenesis and fat mass accumulation in mice. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids. 2018 Feb 28;1863(2):165-76.
Zaichko N.V., Melnik A.V., Yoltukhivskyy M.M., Olhovskiy A.S., Palamarchuk I.V. Hydrogen sulfide: modern aspects of metabolism, biological and medical role. Ukr. Biochem. J. 2014. 86(5). 5-25.
Zayachkivska O, Havryluk O, Hrycevych N, Bula N, Grushka O, Wallace JL. Cytoprotective effects of hydrogen sulfide in novel rat models of non-erosive esophagitis. PloS one. 2014 Oct 21;9(10):e110688.
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