Changes in hydrogen sulfide in rats with hepatic cirrhosis in different stages

Abstract

This study aimed to observe changes in the hydrogen sulfide (H₂S) system in the blood and liver tissue of rats with hepatic cirrhosis at different stages by studying the effect of H₂S on the course of hyperdynamic circulation in rats with hepatic cirrhosis. H₂S concentration in the blood from the portal vein and inferior vena cava of hepatic cirrhosis rat model induced with carbon tetrachloride was detected on the 15th, 30th, and 52nd day. The expression of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) protein, and CBS and CSE mRNA in the liver was detected by immunohistochemistry and reverse transcriptase polymerase chain reaction (RT-PCR), respectively. The results indicated that H₂S concentration in the blood from the portal vein and inferior vena cava of rats with hepatic cirrhosis was significantly lower than that in the control group. H₂S was gradually decreased with the development of the disease and significantly lower in the blood from portal vein than in the blood of inferior vena cava at the mid-stage and the late stage groups. The expression levels of CBS and CSE protein, and CBS and CSE mRNA in the livers with hepatic cirrhosis at different stages were all higher than those in the control group, and the expression gradually increased with the development of the disease. The expression of CBS was lower than CSE in the same stages. The results indicated that the CSE mRNA was expressed predominantly in the cirrhosis groups as compared with CBS mRNA. Among experimental rats, the H₂S system has an important effect on the occurrence and development of hyperdynamic circulation in rats with hepatic cirrhosis. This finding adds to the literature by demonstrating that H₂S protects vascular remodelling in the liver, and that CSE is indispensable in this process.

Keywords

hepatic cirrhosis / hydrogen sulfide / cystathionine β-synthase / cystathionine γ-lyase / portal vein / inferior vena cava / rats

References

[1] ZhangF, JinH, WuL, et al. . Diallyl trisulfide suppresses oxidative stress-induced activation of hepatic stellate cells through production of hydrogen sulfide. Oxid Med Cell Longev, 2017, 2017: 1406726 PMID: 28303169 PMCID: 5337887

[2] BeauchampR J, BusJS, PoppJA, et al. . A critical review of the literature on hydrogen sulfide toxicity. Crit Rev Toxicol, 1984, 13(1): 25-97 PMID: 6378532

[3] GuidottiTL. Hydrogen sulfide. Occup Med (Lond), 1996, 46(5): 367-371

[4] GengB, YangJH, QiYF, et al. . H₂S generated by heart in rat and its effects on cardiac function. Biochem Biophys Res Commun, 2004, 313(2): 362-368 PMID: 14684169

[5] NorrisEJ, CulbersonCR, NarasimhanS, et al. . The liver as a central regulator of hydrogen sulfide. Shock, 2011, 36(3): 242-250 PMID: 21617578 PMCID: 3164993

[6] SwaroopM, BradleyK, OhuraT, et al. . Rat cystathionine beta-synthase. Gene organization and alternative splicing. J Biol Chem, 1992, 267(16): 11455-11461 PMID: 1597473

[7] BazhanovN, AnsarM, IvanciucT, et al. . Hydrogen sulfide: a novel player in airway development, pathophysiology of respiratory diseases and antiviral defenses. Am J Respir Cell Mol Biol, 2017

[8] AslamiH, BeurskensCJ, De BeerFM, et al. . A short course of infusion of a hydrogen sulphide-donor attenuates endotoxemia induced organ injury via stimulation of anti-inflammatory pathways, with no additional protection from prolonged infusion. Cytokine, 2013, 61(2): 614-621 PMID: 23267760

[9] AhmadA, DruzhynaN, SzaboC. Delayed treatment with sodium hydrosulfide improves regional blood flow and alleviates cecal ligation and puncture (CLP)-induced septic shock. Shock, 2016, 46(2): 183-193 PMID: 26863032 PMCID: 4949092

[10] ManiS, CaoW, WuL, et al. . Hydrogen sulfide and the liver. Nitric Oxide, 2014, 41: 62-71 PMID: 24582857

[11] FanHN, WangHJ, RenL, et al. . Decreased expression of p38 MAPK mediates protective effects of hydrogen sulfide on hepatic fibrosis. Eur Rev Med Pharm Sci, 2013, 17(5): 644-652

[12] AbeK, KimuraH. The possible role of hydrogen sulfide as an endogenous neuromodulator. J Neurosci, 1996, 16(3): 1066-1071 PMID: 8558235

[13] WangC, HanJ, XiaoL, et al. . Role of hydrogen sulfide in portal hypertension and esophagogastric junction vascular disease. World J Gastroenterol, 2014, 20(4): 1079-1087 PMID: 24574782 PMCID: 3921533

[14] HosokiR, MatsukiN, KimuraH. The possible role of hydrogen sulfide as an endogenous smooth muscle relaxant in synergy with nitric oxide. Biochem Biophys Res Commun, 1997, 237(3): 527-531 PMID: 9299397

[15] AhmadA, GeroD, OlahG, et al. . Effect of endotoxemia in mice genetically deficient in cystathionine-β-lyase, cystathionine-ß-synthase or 3-mercaptopyruvate sulfurtransferase. Int J Mol Med, 2016, 38(6): 1683-1692 PMID: 27748832 PMCID: 5117757

[16] ColettaC, SzaboC. Potential role of hydrogen sulfide in the pathogenesis of vascular dysfunction in septic shock. Curr Vasc Pharmacol, 2013, 11(2): 208-221 PMID: 23506499

[17] TangG, WuL, LiangW, et al. . Direct stimulation of K(ATP) channels by exogenous and endogenous hydrogen sulfide in vascular smooth muscle cells. Mol Pharm acol, 2005, 68(6): 1757-1764

[18] SzaboC, RansyC, MódisK, et al. . Regulation of mitochondrial bioenergetic function by hydrogen sulfide. Part I. Biochemical and physiological mechanisms. Br J Pharmacol, 2014, 171(8): 2099-2122 PMID: 23991830

[19] ModisK, ColettaC, ErdelyiK, et al. . Intramitochondrial hydrogen sulfide production by 3-mercaptopyruvate sulfurtransferase maintains mitochondrial electron flow and supports cellular bioenergetics. FASEB J, 2013, 27(2): 601-611 PMID: 23104984

[20] PolhemusDJ, LeferDJ. Emergence of hydrogen sulfide as an endogenous gaseous signaling molecule in cardiovascular disease. Circ Res, 2014, 114(4): 730-737 PMID: 24526678 PMCID: 3951140

[21] HuangCW, MoorePK. H₂S synthesizing enzymes: Biochemistry and molecular aspects. Handb Exp Pharmacol, 2015, 230: 3-25 PMID: 26162827

[22] PernaAF, IngrossoD. Low hydrogen sulfide and chronic kidney disease: a dangerous liaison. Nephrol Dial Transplant, 2012, 27(2): 486-493 PMID: 22323660

[23] SchwerCI, StollP, GoebelU, et al. . Effects of hydrogen sulfide on rat pancreatic stellate cells. Pancreas, 2012, 41(1): 74-83 PMID: 21934550

[24] SodhaNR, ClementsRT, FengJ, et al. . The effects of therapeutic sulfide on myocardial apoptosis in response to ischemia-reperfusion injury. Eur J Cardiothorac Surg, 2008, 33(5): 906-913 PMID: 18314343 PMCID: 2424271

[25] FerlitoM, WangQ, FultonWB, et al. . Hydrogen sulfide increases survival during sepsis: protective effect of CHOP inhibition. J Immunol, 2014, 192(4): 1806-1814 PMID: 24403532 PMCID: 3946246

[26] LiXH, DuJB, JinHF, et al. . The regulatory effect of endogenous hydrogen sulfide on pulmonary vascular structure and gasotransmitters in rats with high pulmonary blood flow. Life Sci, 2007, 81(10): 841-849 PMID: 17714736

[27] GeroD, AhmadA, BrunyanszkiA, et al. . 3-Mercaptopyruvate sulfurtransferase deficient mice show accelerated glucose uptake and a dysregulated metabolic profile. Nitric Oxide, 2015, 47(6): S35-S36

[28] ShirozuK, TokudaK, MarutaniE, et al. . Cystathionine γ-lyase deficiency protects mice from galactosamine/lipopolysaccharide-induced acute liver failure. Antioxid Redox Signal, 2014, 20(2): 204-216 PMID: 23758073 PMCID: 3887435

[29] ShengJ, ShimW, WeiH, et al. . Hydrogen sulphide suppresses human atrial fibroblast proliferation and transformation to myofibroblasts. J Cell Mol Med, 2013, 17(10): 1345-1354 PMID: 23945069 PMCID: 4159014