Українська English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

(English title: Physiological Journal)

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. 2025; 71(2): 77-83


THE EFFECT OF GLUTATHIONE ON OXYTOCIN-INDUCED CONTRACTILE ACTIVITY AND BASAL TONE OF THE RAT UTERINE MYOMETRIUM UNDER CONDITIONS OF ENDOTOXEMIA

V.R. Strutynskyi1, O.I. Diachuk2, R.I. Yanchiy1

  1. Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
  2. Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine
DOI: https://doi.org/10.15407/fz71.02.077


Abstract

The naturally occurring endotoxin lipopolysaccharide (LPS) can cause systemic endotoxemia and impair animal reproductive capacity. LPS induces oxidative stress and alters protein, receptor expression, and metabolic pathways in the uterus, impairing its function. The aim of the work was to investigate the effect of exogenous glutathione on oxytocin-induced contractile activity and basal tone of isolated uterine myometrium preparations from rats with LPS-induced experimental endotoxemia. The experiments were performed on isolated longitudinal strips of the uterine horn of mature estrogenic female Wistar rats perfused at 37°C with oxygenated Krebs solution. All testing was performed in isometric mode at an initial set tension of 3 mN. The animals were divided into three groups: control, rats injected with LPS, and rats injected with LPS and glutathione. Experimental endotoxemia was created by intraperitoneal administration of lipopolysaccharide at a dose of 3 mg/kg the day before the experiment. Glutathione was administered intraperitoneally at 52 mg/kg twice, one day and one hour before the experiment. Oxytocin was added to the perfusion solution at a 0.1-100 nmol/L concentration. Oxytocin dose-dependently increased the amplitude of contractions of isolated preparations of rat uterine myometrium with a maximum effect of 26.5%. At a concentration of 100 nmol/L, a significant increase in basal tone and contraction frequency of myometrial strips of 6.5% and 66.8%, respectively, was observed. In LPS-in- duced experimental endotoxemia, the contractile activity of myometrial preparations in response to oxytocin was significantly increased. At the same concentration of oxytocin, the amplitude of contractions and basal tone compared to the control group increased by 3.1 and 2.3 times, respectively, and the frequency of contractions by 71% compared to baseline. Glutathione administration to animals significantly reduced the effect of LPS on oxytocin-induced changes in the contractile activity of the uterine myometrium. The contraction amplitude, basal tone, and contraction frequency in these rats were close to the values in control rats. Hence, in LPS-induced experimental endotoxemia, the amplitude of oxytocin-induced contraction and the basal tone of uterine preparations significantly increased, which was prevented by glutathione administration to the animals. This suggests the possible use of the antioxidant glutathione in endotoxemia to prevent impaired reproductive function in animals.

Keywords: uterine myometrium, contractile activity, lipopolysaccharide, oxytocin, endotoxemia

References

  1. Lu D, Hu W, Tian T, Wang M, Zhou M, Wu C. The mechanism of lipopolysaccharide's effect on secretion of endometrial mucins in female mice during pregnancy. Int J Mol Sci. 2022 sep 1;23(17):9972. CrossRef PubMed PubMedCentral
  2. bariani mv, correa F, Leishman E, Domínguez Rubio AP, Arias A, Stern A, Bradshaw HB, Franchi AM. Resveratrol protects from lipopolysaccharide-induced inflammation in the uterus and prevents experimental preterm birth. Mol Hum Reprod. 2017 Aug 1;23(8):571-81. CrossRef PubMed PubMedCentral
  3. Hadi T, Bardou M, Mace G, Sicard P, Wendremaire M, Barrichon M, Richaud S, Demidov O, Sagot P, Garrido C, Lirussi F. Glutathione prevents preterm parturition and fetal death by targeting macrophage-induced reactive oxygen species production in the myometrium. FASEB J. 2015 Jun;29(6):2653-66. CrossRef PubMed
  4. Du Y, Zeng Y, Li S, Wang Z, Su C, Zhang S, Ren Y, Song T, Zhang M. Mild infection induced by low-dose LPS does not impair follicular development and is beneficial to pregnancy in mice . Front Vet Sci. 2023 Feb 23;9:1051433. CrossRef PubMed PubMedCentral
  5. Bidne KL, Dickson MJ, Ross JW, Baumgard LH, Keat-ing AF. Disruption of female reproductive function by endotoxins. Reproduction. 2018 Apr;155(4):R169-81. CrossRef PubMed
  6. Ross RG, Sathishkumar K, Naik AK, Bawankule DU, Sarkar SN, Mishra SK, Prakash VR. Mechanisms of lipopolysaccharide-induced changes in effects of contractile agonists on pregnant rat myometrium. Am J Obstet Gynecol. 2004 Feb;190(2):532-40. Вплив глутатіону на окситоциніндуковану скоротливу активність і базальний тонус міометрія матки щурів за умов ендотоксемії 83
  7. Ouwendijk RJT. Eicosanoids, endotoxins and liver disease. Thesis Rotterdam. Proefschrift ter verkrijging van de graad van doctor in de geneeskunde. 1985:203.
  8. Yin Z, Su J, Fei J, Li T, Li D, Cao Y , Khalil RA. Preserved oxytocin-induced myometrium contraction and sensitivity to progesterone inhibition following rat uterus thermal insult. Impact on fertility. Biochem Pharmacol. 2022 Oct;204:115244. CrossRef PubMed
  9. Veiga GA, Milazzotto MP, Nichi M, Lúcio CF, Silva LC, Angrimani DS, Vannucchi CI. Gene expression of estrogen and oxytocin receptors in the uterus of pregnant and parturient bitches. Braz J Med Biol Res. 2015 Apr;48(4):339-43. CrossRef PubMed PubMedCentral
  10. Yulia A, Johnson MR. Myometrial oxytocin receptor expression and intracellular pathways. Minerva Ginecol. 2014 Jun;66(3):267-80.
  11. Yurttancikmaz ET, Ozcan P, Tanoglu FB, Tok OE, Timur HT, Cetin C. Protective effect of glutathione administration on ovarian function in female rats with cyclophosphamide-induced ovarian damage. Gynecol Obstet Invest. 2024;89(2):120-30. CrossRef PubMed PubMedCentral
  12. Homma T, Fujii J. application of glutathione as anti-oxidative and anti-aging drugs. Curr Drug Metab. 2015;16(7):560-71. CrossRef PubMed
  13. Guoyao Wu, Yun-Zhong Fang, Sheng Yang, Joanne R Lupton, Nancy D Turner. Glutathione metabolism and its implications for health. J Nutr. 2004 Mar;134(3):489-92. CrossRef PubMed
  14. Strutynska N, Goshovska Y , Mys L, Strutynskyi R, Luch-kova A, Fedichkina R, Okhai I, Korkach Y , Sagach V . Glutathione restores the mitochondrial redox status and improves the function of the cardiovascular system in old rats. Front Physiol. 2023 Jan 9;13:1093388. CrossRef PubMed PubMedCentral
  15. Marí M, de Gregorio E, de Dios C, Roca-Agujetas V , Cu-carull B, Tutusaus A, Morales A, Colell A. mitochondrial glutathione: recent insights and role in disease. Antioxidants (Basel). 2020 Sep 24;9(10):909. CrossRef PubMed PubMedCentral
  16. Strutynskyi R, Strutynska N, Mys L, Goshovska Y , Kork-ach Y , Fedichkina R, Okhai I, Strutynskyi V , Sagach V . Glutathione upregulates the expression of K ATP channels and vasorelaxation responses and inhibits mPTP opening and oxidative stress in the Heart mitochondria of old rats. Biomed Res Int. 2023 May 24;2023:3562847. CrossRef PubMed PubMedCentral
  17. Strutynska NA, Goshovska YV , Korkach YP, Mys LA, Strutynskyi RB, Sagach VF. Effects of glutathione on the expression of ATP-sensitive potassium channels, mitochondrial pores, and on oxidative stress in the heart of old rats. Fiziol Zh. 2020; 66(6): 66-73. CrossRef
  18. Ross RG, Sathishkumar K, Naik AK, Bawankule DU, Sarkar SN, Mishra SK, Prakash VR. Mechanisms of lipopolysaccharide-induced changes in effects of contractile agonists on pregnant rat myometrium. Am J Obstet Gynecol. 2004 Feb;190(2):532-40. CrossRef PubMed
  19. Nasibian LS, Sotkis HV , Tzugorko OM, Philyppov IB, Shuba YM. Рeptidoglycan of staphylococcus aureus alters the myometrial contractility of non-pregnant rats trough increasing intracellular calcium levels. Fiziol Zh. 2020; 66(6): 56-65. CrossRef
  20. Strutynskyi RB. Protective properties of opening ATP-sensitive potassium channels. Fiziol Zh. 2019;65(3):73- 85. CrossRef
  21. V oitychuk OI, Strutynskyi RB, Yagupolskii LМ, Tinker A, Moibenko OO, Shuba YM. Sarcolemmal cardiac K ATP channels as a target for the cardioprotective effects of the fluorine-containing pinacidil analogue flocalin. Br J Pharmacol. 2011; 162(3):701-11. CrossRef PubMed PubMedCentral
  22. Xu C, You X, Gao L, Zhang L, Hu R, Hui N, Olson DM, Ni X. Expression of ATP-sensitive potassium channels in human pregnant myometrium. Reprod Biol Endocrinol. 2011 Mar 21;9:35. CrossRef PubMed PubMedCentral
  23. Hong SH, Kyeong KS, Kim CH, Kim YC, Choi W, Yoo RY , Kim HS, Park YJ, Ji IW, Jeong EH, Kim HS, Xu WX, Lee SJ. Regulation of myometrial contraction by ATP-sensitive potassium (KATP) channel via activation of SUR2B and Kir 6.2 in mouse. J Vet Med Sci. 2016 Aug 1;78(7):1153-9. CrossRef PubMed PubMedCentral
  24. Yurttancikmaz ET, Ozcan P, Tanoglu FB, Tok OE, Timur HT, Cetin C. Protective effect of glutathione administration on ovarian function in female rats with cyclophosphamide-induced ovarian damage. Gynecol Obstet Invest. 2024;89(2):120-30. CrossRef PubMed PubMedCentral

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2025.