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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(3): 3-9


N.O. Dorofeeva, Yu.P. Korkach, P.R. Sharipov, V.F. Sagach

    O.O. Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv, Ukraine


Cerebral ischemia is a neurogenerative disoder that leads to partial or general paralysis and subsequent disability. The development of oxidative-nitrosative stress on the background of insufficient production of nitric oxide (NO) and hydrogen sulfide (H2S) are the main reasons behind the pathogenesis of focal ischemia-reperfusion and cerebrocardial syndrome. We studied the combined use of propargylglycine and L-cysteine as drugs that prevent oxidative and nitrosative stress and are activators of gasotransmitters - NO and H2S in the heart tissues of rats with focal ischemia. It was shown that focal ischemiareperfusion was accompanied by a significant increase in the heart of rats calcium-independent inducible synthesis of NO (iNOS) and an increase in markers of oxidative stress (superoxide anion radical, hydroxyl radical, diene conjugates) NO-synthase (cNOS). This caused disruption of nitric oxide synthesis due to the uncoupling state of cNOS in the rat heart. The use of a combination of DL-proparlgylglycine (11.31 mg/ kg) and L-cysteine (112.1 mg / kg) 40 min before the modeling of focal ischemia significantly reduced the activity of iNOS and the content of markers of oxidative metabolism in the heart of adult rats and increased the constitutive synthesis of NO, which led to restoration of the cNOS incoupling. We observed activation of endogenous synthesis of H2S, which interacts closely with the nitric oxide system and is a powerful antioxidant. It should also be noted an increase in animal survival after 24 h by 25%. Thus, the combined use of propargylglycine and Lcysteine in rats prevented disruption of NO and H2S synthesis in cardiac tissues in ishemia-reperfusion due to a slowing of the development of oxidative stress, which helped to restore cNOS coupling.

Keywords: DL-propargylglycine; L-cysteine; oxidative stress; inducible NO synthase; constitutive NO synthases; hydrogen sulfide; focal cerebral ischemia-reperfusion.


  1. Johnson W, Onuma O, Owolabi M, Sachdev S. Stroke: a global response is needed. Bull World Health Organ. 2016;94(9):634-34A. CrossRef PubMed PubMedCentral
  2. Nanetti L, Raffaelli F, Vignini A, Perozzi C, Silvestrini M, Bartolini M, et al. Oxidative stress in ischaemic stroke. Eur J Clin Invest. 2011;41(12):1318-22. CrossRef PubMed
  3. Zhdanov GN, Gerasimova MM. Study of the content of pro-inflammatory and anti-inflammatory cytokines in the blood serum of patients in the acute period of ischemic stroke. Cytokin Inflammat. 2006;5(1):27-30.
  4. Deb P, Sharma S, Hassan KM. Pathophysiologic mechanisms of acute ischemic stroke: An overview with emphasis on therapeutic significance beyond thrombolysis. Pathophysiology. 2010;17(3):197-218. CrossRef PubMed
  5. Scheitz JF, Nolte CH, Doehner W, Hachinski V, Endres M. Stroke-heart syndrome: clinical presentation and underlying mechanisms. Lancet Neurol. 2018; 17(12):1109-20. CrossRef
  6. Fedichkina RA, Goshovska YV, Sagach VF. Effect of modulation of L-cysteine metabolism on the implementation of Frank-Starling mechanism. Fiziol Zh. 2019;65(3S):82. [Ukrainian].
  7. Sharipov RR, Kotsiuruba AV, Sahach VF. Induction of oxidative stress in heart mitochondria in brain focal ischemia-reperfusion and protective effect of ecdysterone. Fiziol Zh. 2014;60(3):11-7. [Ukrainian]. CrossRef PubMed
  8. Mys L, Strutynska N, Goshovska Y, Sagach V. Stimulation of the endogenous hydrogen sulfide synthesis suppresses oxidative-nitrosative stress and restores endothelialdependent vasorelaxation in old rats. Can J Physiol Pharmacol. 2020;98(5):275-81. CrossRef PubMed
  9. Svenson A. A rapid and sensitive spectrophotometric method for determination of hydrogen sulfide with 2, 2′-dipyridyl disulfide. Anal Biochem. 1980;107(1):51-5. CrossRef
  10. Lee J-M, Zipfel GJ, Choi DW. The changing landscape of ischaemic brain injury mechanisms. Nature. 1999; 399(6738):A7-14. CrossRef PubMed
  11. Erecińska M, Silver IA. Tissue oxygen tension and brain sensitivity to hypoxia. Respir Physiol. 2001;128(3): 263-76. CrossRef
  12. Iadecola C, Anrather J. The immunology of stroke: from mechanisms to translation. Nat Med. 2011;17(7):796-808. CrossRef PubMed PubMedCentral
  13. Narne P, Pandey V, Phanithi PB. Role of nitric oxide and hydrogen sulfide in ischemic stroke and the emergent epigenetic underpinnings. Mol Neurobiol. 2019;56(3):1749-69. CrossRef PubMed
  14. Vásquez-Vivar J, Kalyanaraman B, Martásek P. The role of tetrahydrobiopterin in superoxide generation from eNOS: enzymology and physiological implications. Free Radic Res. 2003;37(2):121-7. CrossRef PubMed
  15. Galougahi KK, Liu C-C, Gentile C, Kok C, Nunez A, Garcia A, et al. Glutathionylation mediates angiotensin II-induced eNOS uncoupling, amplifying NADPH oxidase-dependent endothelial dysfunction. J Am Heart Assoc. 2014;3(2):e000731. CrossRef PubMed PubMedCentral
  16. Hill BG, Bhatnagar A. Protein S-glutathiolation: redoxsensitive regulation of protein function. J Mol Cell Cardiol. 2012;52(3):559-67. CrossRef PubMed PubMedCentral
  17. Brandes RP, Fleming I, Busse R. Endothelial aging. Cardiovascul Res. 2005;66(2):286-94. CrossRef PubMed
  18. Altaany Z, Ju Y, Yang G, Wang R. The coordination of S-sulfhydration, S-nitrosylation, and phosphorylation of endothelial nitric oxide synthase by hydrogen sulfide. Sci Signal. 2014;7(342):ra87-ra87. CrossRef PubMed
  19. Kimura Y, Kimura H. Hydrogen sulfide protects neurons from oxidative stress. FASEB J. 2004;18(10):1165-7. CrossRef PubMed
  20. Kimura Y, Shibuya N, Kimura H. Sulfite protects neurons from oxidative stress. Br J Pharmacol. 2019;176(4): 571-82. CrossRef PubMed PubMedCentral
  21. Fedichkina R, Goshovska Y, Sagach V. P86 stimulation of endogenous glutathione synthesis prevent postreperfusion NOS uncoupling, oxidative nitrosative stress and cardiodynamic disturbances in rats. Cardiovascul Res. 2018;114(Suppl. 1). CrossRef

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