Blazhchenko V.V., Zaichko N.V.

HYGIENE AND ECOLOGY

Scentific article

Introduction. The role of hydrogen sulfide (H2 S) in the pathochemistry of obesity and its complications remains the subject of active research in biology and medicine. The kidneys are one of the key target organs that suffer from obesity. Physiologically, H2 S is synthesized in the kidneys, and is involved in the regulation of all renal functions, lipid metabolism and adipogenesis. The search for correctors of H2 S metabolism, which would provide nephroprotection in obesity, would not activate lipogenesis and adipogenesis, is relevant.The aim of study: to establish the effect of zinc sulfate, sodium thiosulfate, lipoic acid, taurine on the expression of enzymes of hydrogen sulfide synthesis, mediators of inflammation, fibrogenesis in the kidneys of rats with diet-induced obesity. Object and methods of research. The experiments were performed on 60 white male laboratory rats in accordance with the principles of bioethics (Strasbourg, 1986). Obesity was simulated by a high-calorie high-fat diet (4.33 kcal/g, 39.5 % fat) for 70 days. Control rats received standard feed (2.71 kcal/g, 10.8 % fat). Metabolic correctors (zinc sulfate, sodium thiosulfate, lipoic acid, taurine) were administered intravenously from the 56th to the 70th day. The level of cystatin C in the blood was determined, the expression of H2 S‑synthesizing enzyme genes (CSE, CBS), IGF1 and TNFα levels were determined in the kidneys. Statistical processing was performed in the package IBM Statistics SPSS 26. Results. In obese rats, increased serum cystatin C levels, decreased levels of CSE and CBS gene expression, increased levels of inflammatory and fibrogenesis mediators (IGF1, TNFα) were found. Inverse associations between the level of gene expression of H2 S‑synthesizing enzymes in the kidneys and biochemical markers of kidney damage have been identified. Zinc sulfate (124 mg/kg), sodium thiosulfate (300 mg/kg), lipoic acid (100 mg/kg), and taurine (100 mg/kg) decreased cystatin C, IGF1, and TNFα levels in obese rats. Zinc sulfate and lipoic acid increased the expression of CSE, CBS genes in the kidneys of obese rats, thiosulfate and taurine did not cause this effect. The introduction of any of the correctors did not aggravate the signs of obesity. Conclusions: Decreased expression of H2 S synthesis enzymes is associated with activation of inflammatory and fibrotic processes in the kidneys under obesity. Zinc sulfate, lipoic acid, thiosulfate, taurine reduce biochemical changes in the kidneys, but show different activity in influencing the expression of H2 S metabolic enzymes.

hydrogen sulfide, obesity, kidney, inflammation, fibrosis.

1. Comas F, Latorre J, Ortega F, Arnoriaga Rodríguez M, Kern M, Lluch A, et al. Activation of endogenous h2 s biosynthesis or supplementation with exogenous H2 S enhances adipose tissue adipogenesis and preserves adipocyte physiology in humans. Antioxid Redox Signal. 2021 Aug 10;35(5):319–340. DOI: https://doi.org/10.1089/ars.2020.8206.
2. Comas F, Moreno-Navarrete JM. The impact of H2S on obesity-associated metabolic disturbances. Antioxidants (Basel). 2021 Apr 21;10(5):633. DOI: https://doi.org/10.3390/antiox10050633.
3. Wei L, LeeY, Yu Y, Xu M, Chen H, LeeL, et al. Obesity-related glomerulopathy: from mechanism to therapeutic target. Diabetes Metab Syndr Obes. 2021 Oct 28;14:4371–4380. DOI: https://doi.org/10.2147/DMSO. S 334199.
4. Yang S, Cao C, Deng T, Zhou Z. Obesity-related glomerulopathy: A latent change in obesity requiring more attention. Kidney Blood Press Res. 2020 Jun 4;45(4):510–522. DOI: https://doi.org/10.1159/000507784.
5. Cao X, Bian JS. The role of hydrogen sulfide in renal system. Front Pharmacol. 2016 Oct 18;7:385. DOI: https://doi.org/10.3389/ fphar.2016. 00385.
6. Zhang H, Zhao H, Guo N. Protective effect of hydrogen sulfide on the kidney (Review). Mol Med Rep. 2021 Oct;24(4):696. DOI: https://doi.org/10.3892/ mmr.2021.12335.
7. Koniukh S, Voloshchuk N, Melnyk A, Domin I. Hydrogen sulfide metabolism and its role in kidney function in a rat model of chronic kidney disease. Health Prob Civil. 2020 Jun 19;14(4):289–297. DOI: https://doi.org/10.5114/ hpc.2020.96571.
8. Ngowi EE, Sarfraz M, Afzal A, Khan NH, Khattak S, Zhang X, et al. Roles of hydrogen sulfide donors in common kidney diseases. Front Pharmacol. 2020 Nov 19;11:564281. DOI: https://doi.org/10.3389/fphar.2020.56428.
9. Wu D, Gao B, LeeM, Yao L, Wang S, Chen M, et al. Hydrogen sulfide mitigates kidney injury in high fat diet-induced obese mice. Oxid Med Cell Longev. 2016 Jun 19;2016:2715718. DOI: https://doi.org/10.1155/2016/ 2715718.
10. Geng B, Cai B, Liao F, Zheng Y, Zeng Q, Fan X, et al. Increase or decrease hydrogen sulfide exert opposite lipolysis, but reduce global insulin resistance in high fatty diet induced obese mice. PLoS One. 2013 Sep 13;8(9): e73892. DOI: https://doi.org/10.1371/ journal.pone.0073892.
11. Yang G, Ju Y, Fu M, Zhang Y, Pei Y, Racine M, et al. Cystathionine gamma-lyase/hydrogen sulfide system is essential for adipogenesis and fat mass accumulation in mice. Biochim Biophys Acta Mol Cell Biol Lipids. 2018 Feb;1863(2):165–176. DOI: https://doi. org/10.1016/j.bbalip.2017.11.008.
12. Khorsandi H, Nikpayam O, Yousefi R, Parandoosh M, Hosseinzadeh N, Saidpour A, et al. Zinc supplementation improves body weight management, inflammatory biomarkers and insulin resistance in individuals with obesity: a randomized, placebo-controlled, double-blind trial. Diabetol Metab Syndr. 2019 Dec 2;11:101. DOI: https://doi.org/10.1186/s13098–019–0497–8.
13. Namazi N, Larijani B, Azadbakht L. Alpha-lipoic acid supplement in obesity treatment: A systematic review and meta-analysis of clinical trials. Clin Nutr. 2018 Apr;37(2):419–428. DOI: https://doi.org/10.1016/j.clnu.2017.06.002.
14. Kim KS, Jang MJ, Fang S, Yoon SG, Kim IY, Seong JK, et al. Anti-obesity effect of taurine through inhibition of adipogenesis in white fat tissue but not in brown fat tissue in a high-fat diet-induced obese mouse model. Amino Acids. 2019 Feb;51(2):245–254. DOI: https://doi.org/10.1007/s00726–018–2659–7.
15. Hsu CN, Hou CY, Chang-Chien GP, Lin S, Yang HW, Tain YL. Sodium thiosulfate improves hypertension in rats with adenine-induced chronic kidney disease. Antioxidants (Basel). 2022 Jan 11;11(1):147. DOI: https://doi.org/10.3390/antiox11010147.
16. Konopelniuk VV, Goloborodko II, Ishchuk TV, Synelnyk TB, Ostapchenko LI, Spivak MY, et al. Efficacy of Fenugreek-based bionanocomposite on renal dysfunction and endogenous intoxication in high-calorie diet-induced obesity rat model-comparative study. EPMA J. 2017 Jun 16;8(4):377–390. DOI: https://doi.org/10.1007/s13167–017–0098–2.
17. Huang P, Shen Z, Yu W, Huang Y, Tang C, Du J, et al. Hydrogen sulfide inhibits high-salt diet-induced myocardial oxidative stress and myocardial hypertrophy in Dahl rats. Frontiers in pharmacology. 2017 Mar 16;8:128. DOI: https://doi.org/10.3389/ fphar.2017.00128$.
18. Sharma I, Liao Y, Zheng X, Kanwar YS. New pandemic: obesity and associated nephropathy. Front Med (Lausanne). 2021 Jun 29;8:673556. DOI: https://doi.org/10.3389/fmed.2021.673556.
19. Niu H, LeeY, LeeH, Chi Y, Zhuang M, Zhang T, et al. Matrix metalloproteinase 12 modulates high-fat-diet induced glomerular fibrogenesis and inflammation in a mouse model of obesity. Sci Rep. 2016 Jan 29;6:20171. DOI: https://doi.org/10.1038/srep20171.
20. Rangel Silvares R, Nunes Goulart da Silva Pereira E, Eduardo Ilaquita Flores E, Lino Rodrigues K, Ribeiro Silva A, Gonçalvesde-Albuquerque CF, et al. High-fat diet-induced kidney alterations in rats with metabolic syndrome: endothelial dysfunction and decreased antioxidant defense. Diabetes Metab Syndr Obes. 2019 Sep 6;12:1773–1781. DOI: https://doi.org/10.2147/DMSO. S 211253.
21. Liu S, Da J, Yu J, Dong R, Yuan J, Yu F, et al. Renal tubule ectopic lipid deposition in diabetic kidney disease rat model and in vitro mechanism of leptin intervention. J Physiol Biochem. 2022 Feb 22. DOI: https://doi.org/10. 1007/s13105–022–00874–9.
22. Lee HJ, Mariappan MM, Norton L, Bakewell T, Feliers D, Oh SB, et al. Proximal tubular epithelial insulin receptor mediates high-fat diet-induced kidney injury. JCI Insight. 2021 Feb 8;6(3): e143619. DOI: https://doi.org/10. 1172/jci.insight.143619.
23. Dong R, Yu J, Yu F, Yang S, Qian Q, Zha Y. IGF‑1/IGF‑1R blockade ameliorates diabetic kidney disease through normalizing Snail1 expression in a mouse model. Am J Physiol Endocrinol Metab. 2019 Oct 1;317(4): E 686-E 698. DOI: 10.1152/ajpendo.00071.2019.

«Bulletin of problems biology and medicine» Issue 2 Part 1 (164), 2022 year, 114-125 pages, index UDK 546.221.1:616.61–056.52:612.08

10.29254/2077-4214-2022-2-1-164-114-125