Українська English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2021; 67(5): 11-20

Role of hydrogen sulfide in the regulation of respiration, blood flow and bile secretory function of the liver

P.I. Yanchuk, I.V. Komarov, Y.А. Levadianska, L.O. Slobodianyk, S.P. Veselsky, T.V. Vovkun, L.Ya. Shtanova, E.M. Reshetnik

    Taras Shevchenko National University of Kyiv, Ukraine


In acute experiments on laboratory rats, intra-portal administration of L-cysteine (20 mg/kg), the precursor of hydrogen sulfide synthesis, stimulated oxygen consumption of liver by 38.6% and reduced oxygen tension by 37.1%. Activation of tissue respiration occurred due to the strengthening of oxygen-dependent synthetic processes in liver, in particular those associated with mitochondrial enzyme-catalysed bile acid biosynthesis through the acidic pathway. The concentrations of taurocholic acid and mixtures of taurodeoxycholic and taurohenodeoxycholic acids increased by 10.3 and 17.9%, respectively, compared to the initial levels. In addition, the level of free cholesterol was decreased by 33.9% and esterification processes were intensified, as indicated by an increase in the concentration of esterified cholesterol by 22.6% in the bile of rats. The latter was to some extent confirmed by a decrease in the level of free bile acids (by 15.8%) involved in the biosynthesis of cholesterol esters and intensification of tissue respiration in the liver. L-cysteine dilated intrahepatic vessels, resulting in a significant decrease of the systemic blood pressure and blood pressure in the portal vein by 17.6 and 24.5%, respectively. L-cysteine increased the rate of local blood flow in the liver and blood supply by 28.2 and 24.4%, respectively. Blockade of cystathionine-γ-lyase by DL-propargylglycine (11 mg/kg) significantly inhibited the L-cysteine-induced tissue respiration and bile acid biosynthesis in the liver. Administration of DL-propargylglycine resulted in constriction of blood vessels of the liver and, as a consequence, to an increased blood pressure and a decreased blood flow rate in tissue. Our data point to an involvement of hydrogen sulfide in the regulation of liver tissue respiration and bile secretory function.

Keywords: hydrogen sulfide; L-cysteine; liver; oxygen tension and consumption; bile secretion; bile acids; cholesterol; lipids; tissue blood flow; blood supply; portal pressure


  1. Wang R. Physiological implication of hydrogen sulfide: a whiff exploration that blossomed. Physiol Rev. 2012; 92(2):791-896. CrossRef PubMed
  2. Li M, Xu C, Shi J, Ding J, et al. Fatty acids promote fatty liver disease via the dysregulation of 3-mercaptopy- ruvatesulfurtransferase/hydrogen sulfide pathway. Gut. 2018 Dec;67(12):2169-80. CrossRef PubMed PubMedCentral
  3. Donnarumma E, Trivedi RK, and Lefer DJ. Protective actions of H2S in acute myocardial infarction and heart failure. Compr Physiol. 2017;7(2): 583-602. CrossRef PubMed
  4. Wang J, Wang W, Li S, Han Y, Zhang P, Meng G, et al. Hydrogen sulfide as a potential target in preventing sper- matogenic failure and testicular dysfunction. Antioxid Redox Signal. 2018; 28(16):1447-62. CrossRef PubMed
  5. Semenykhina OM, Bazilyuk OV, Korkach YP, Sagach VF. Mechanisms of hydrogen sulfide effects on contractile activity of vascular smooth muscle in rats. Fiziol. Zh. 2011;57(4):3-12. [Ukrainian]. CrossRef
  6. Mys LA, Strutynska NA, Goshovska YV, Sagach VF. Stimulation of the endogenous hydrogen sulfide synthe- sis suppresses oxidative-nitrosative stress and restores endothelial-dependent vasorelaxation in old rats. Can J Physiol Pharmacol. 2020;98(5):275-81. CrossRef PubMed
  7. Xiao Yu Tiana, Wing Tak Wonga, et al. NaHS relaxes rat cerebral artery in vitro via inhibition of l-type voltage- sensitive Ca2+ channel. Pharmacol Res. 2012; 65:239-46. CrossRef PubMed
  8. Adrienne L, King AL, Lefer DJ. Cytoprotective actions of hydrogen sulfide in ischaemia-reperfusion injury. Exp. Physiol. 2011;96(9):840-6. CrossRef PubMed
  9. Renga B. Hydrogen sulfide generation in mammals: the molecular biology of cystathionine-beta-synthase (CBS) and cystathionine-gamma-lyase (CSE). Inflamm. Allergy Drug Targets. 2011;10:85-91. CrossRef PubMed
  10. Robert K, Nehme J, Bourdon E, et al. Cystathionine beta synthase deficiency promotes oxidative stress, fibrosis, and steatosis in mice liver. Gastroenterology. 2005;128:1405-15. CrossRef PubMed
  11. Fiorucci S, Distrutti E, Cirino G, Wallace JL. The emerging roles of hydrogen sulfide in the gastrointestinal tract and liver. Gastroenterology. 2006;131:259-71. CrossRef PubMed
  12. Esteller A. Physiology of bile secretion. World J Gastro- enterol. 2008;14, (37): 5641-9. CrossRef PubMed PubMedCentral
  13. Pellicoro A. Human and rat bile acid-CoA: amino acid N- acyltransferase are liver-specific peroxisomal enzymes: implications for intracellular bile salt transport. Hepatol- ogy. 2007;45(2):340-8. CrossRef PubMed
  14. Hofmann AF. Bile acids: chemistry, pathochemistry, biol- ogy, pathobiology, and therapeutics. Cell Mol Life Sci. 2008;65(16):2461-83. CrossRef PubMed
  15. Yanchuk PI, Bondzyk OV, Reshetnik YeM, Veselsky SP. Effect of L-arginine on oxygen balance of the liver and the bile secretion function. Fiziol Zh. 2013;59(2):31-8. [Ukrainian]. CrossRef PubMed
  16. Yanchuk PI, Athamnah SM, Reshetnik YM, еt al. Con- tribution of serotonin to regulation of tissue respiration and bile secretory function of the liver. Fiziol Zh. 2015;61(2):103-11. [Ukrainian].
  17. Lefebvre P, Cariou B, Lien F. Role of bile acids and bile acid receptors in metabolic regulation. Physiol Rev. 2009;89(1),147-91. CrossRef PubMed
  18. Dikkers, A. Biliarycholesterol secretion: more than a sim- ple ABC. World J Gastroenterol. 2010;16(47), 5936-45.
  19. Li Y, Wang X, Shen Z. Traditional Chinese medicine for lipid metabolism disorders. Am J Transl Res. 2017;9(5), 2038-49.
  20. Sarathi Mania, Wei C, et al. Hydrogen sulfide and the liver. Nitric Oxide. 2014;10:1006-16. CrossRef PubMed
  21. Fujii K, Sakuragawa T, Kashiba M, et al. Hydrogen sulfide as an endogenous modulator of biliary bicarbo- nate excretion in the rat liver. Antioxid Redox Signal. 2005;7:788-94. CrossRef PubMed
  22. Haouzi Р, Sonobe Т. Cardiogenics hock induced reduction in cellular O2 delivery as a hall markofacute H2S intoxica- tion. Clin Toxicol (Philadelphia, Pa). 2015; 53(4), 416-7. CrossRef PubMed PubMedCentral
  23. Abou-Hamdan A, Guedouari-Bounihi H, Lenoir V. Oxidation of H2S in mammalian cells and mitochondria. Methods Enzymol. 2015;554,201-28. CrossRef PubMed
  24. Norris EJ, Culberson CR, Narasimhan S. The liver as a central regulator of hydrogen sulfide. Shock. 2011;36 (3), 242-50. CrossRef PubMed PubMedCentral
  25. Melnichuk DO, Tomchuk VA, Yanchuk PI, et al. Methods of investigation the functional state of the liver and biliary system. Kyiv: NULES of Ukraine. 2015.
  26. Fiorucci S, Antonelli E, Distrutti E, et al. Inhibition of hydrogen sulfide generation contributes to gastric injury caused by non-steroidal anti-inflammatory drugs. Gas- troenterology. 2005;129:1210-24. CrossRef PubMed
  27. Melnyk AB, Voloschuk NO, Pentyuk NO, Zaichko KO. The role of hydrogen sulphide and amino acids sulfur- containing in regulation tone of vascular smooth muscle wall the rats. Neurophysiology. 2010;42(2):126-31. [Ukrainian]. CrossRef
  28. Jang G, Wu L, Liang W, Wang R. Direct stimulation of K(ATP) channels by exogenous and endogenous hydrogen sulfide in vascular smooth muscle cells. Mol Pharmacol. 2005;68:1757-64. CrossRef PubMed
  29. Hedegaard ER, Gouliaev A, Winther AK, Arcanjo DD, Aalling M, Renaltan NS, et al. Involvement of potas- sium channels and calcium-independent mechanisms in hydrogen sulfide-induced relaxation of rat mesenteric small arteries. J Pharmacol Exp Ther. 2016;356(1):53-63. CrossRef PubMed
  30. Jackson-Weaver O, Osmond JM, Naik JS, Gonzalez Bosc LV, Walker BR, Kanagy NL. Intermittent hypoxia in rats reduces activation of Ca2+ sparks in mesenteric arteries. Am J Physiol Heart Circ Physiol. 2015; 309(11):H1915-22. CrossRef PubMed PubMedCentral
  31. Drachuk KO, Kotsiuruba AV, Baziliuk OV, Stepanenko LH, Sahach VF. Propargylglycine restores endothelium- dependent relaxation of aortic smooth muscles in old rats. Fiziol Zh. 2014;60(4):3-10. [Ukrainian]. CrossRef PubMed
  32. Strutynska NA, Korkach YuP, Mys LА, Luchkova АYu, Sagach VF. L-cysteine stimulates endogenous hydrogen sulfide synthesis, suppresses oxidative stress and mitochondrial permeability transition pore opening in the heart of old rats. Fiziol Zh. 2020;66(2-3):3-12. [Ukrainian]. CrossRef

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2024.