Ukr.Biochem.J. 2020; Volume 92, Issue 1, Jan-Feb, pp. 75-83

doi: https://doi.org/10.15407/ubj92.01.075

Indexes of nitric oxide system in experimental antiphospholipid syndrome

04.02.2020   Uncategorized   No comments

O. Z. Yaremchuk, K. A. Posokhova, І. P. Kuzmak,
M. I. Kulitska, I. М. Klishch, M. M. Korda

I. Horbachevsky Ternopil National Medical University, Ukraine;
e-mail: yaremchuk@tdmu.edu.ua

Received: 11 November 2019; Accepted: 21 January 2020

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the presence of antibo­dies to negatively charged membrane phospholipids (aPL).  Endothelial dysfunction is one of the most dangerous­ APS manifestations followed by thrombosis, placental insufficiency and often foetal death due to circulatory disorders in placenta blood vessels. It is established that synthesis and bioavailability of nitric oxide (NO) in the endothelium are impaired at APS, but the role of NO system in pregnancy failure at this pathology remains ambiguous. The aim of this research was to estimate the indexes of the nitric oxide system in animals with an experimental antiphospholipid syndrome before pregnancy and on the 18th day of pregnancy, without­ treatment and under treatment with nitric oxide synthesis modulators (L-arginine and aminoguanidine). In the blood serum and liver of the BALB/c mice with experimental APS, the content of eNOS and iNOS– by ELISA and the level of NO2– and NO3– with the use of Gris reagent were determined before pregnancy and on the 18th day of pregnancy. The data obtained indicate the relative inefficient NO production by eNOS and NO hyperproduction by iNOS in the blood serum and liver of mice in the pathogenesis of experimental APS. Thus, in mice with APS before pregnancy and on the 18th day of the pregnancy, the eNOS content and NO2– level were decreased while the iNOS content and NO3– level were increased compared to the indexes in the control animal group. L-arginine administration to the animals with APS at the follow-up periods resulted in an increased eNOS content and NO2–, NO3– levels in blood serum and liver with the simultaneous decrease in iNOS content in the liver as compared to indexes in untreated mice with APS. The combined use of L-arginine and selective iNOS inhibitor aminoguanidine caused a significant increase in eNOS content and a decrease in iNOS content followed by normalization of NO2– and NO3– levels in blood and liver of mice with  experimental APS before pregnancy and on the 18th day of pregnancy compared to untreated mice with APS.

Keywords: , , , , ,

References:

  1. Collict M, Buhagiar WS, Mercieca C, Thake J. Catastrophic antiphospholipid syndrome in pregnancy: a life-threatening condition. BMJ Case Rep. 2019;12(9):e230863.  PubMed, PubMedCentral, CrossRef
  2. Fleetwood T, Cantello R, Comi C. Antiphospholipid Syndrome and the Neurologist: From Pathogenesis to Therapy. Front Neurol. 2018;9:1001.   PubMed, PubMedCentral, CrossRef
  3. Nasonov E. L. Antiphospholipid syndrome. M.: Litterra, 2004. 440 p. (In Russian).
  4. Gornitskaya OV. The antiphospholipid syndrome. Exp Clin Physiol Biochem. 2008;41(1): 61-70. (In Russian).
  5. Arachchillage DRJ, Laffan M. Pathogenesis and management of antiphospholipid syndrome. Br J Haematol. 2017;17(2):181-195. PubMed, CrossRef
  6. Posokhova KA, Sak IYu, Sampara SR. Obstetric antiphospholipid syndrome and nitriс oxide system (Review of the literature and the results of the research). Med Chem. 2014;16(1):73-80. (In Ukrainian).
  7. Favaloro EJ. Variability and diagnostic utility of antiphospholipid antibodies including lupus anticoagulants. Int J Lab Hematol. 2013;35(3):269-74. PubMed, CrossRef
  8. Gris JC, Bouvier S. Antiphospholipid syndrome: looking for a refocusing. Thromb Res. 2013;131(Suppl 1):S28-S31. PubMed,  CrossRef
  9. Ahmadzada VA. Pregnancy and childbirth in antiphospholipid syndrome: clinical course and perinatal mortality. Med Novosti. 2011;(5):81-85. (In Russian).
  10. Kharkevich ON, Latnikova EA. Management of pregnancy and childbirth in patients with antiphospholipid syndrome. Med Novosti. 2011;(2):51-59. (In Russian).
  11. Shlyakhtenko TN, Alyab’yeva EA, Arzhanova ON, Selkov SA, Pluzhnikova TA, Chepanov SV. Antiphospholipid syndrome in miscarriage. J Obstet Womens Dis. 2015;64(5):69-76. (In Russian). CrossRef
  12. Ames PRJ, Batuca JR, Ciampa A, Iannaccone L, Alves JD. Clinical relevance of nitric oxide metabolites and nitrative stress in thrombotic primary antiphospholipid syndrome. J Rheumatol. 2010;37(12):2523-30.  PubMed, CrossRef
  13. Ramesh S, Morrell CN, Tarango C, Thomas GD, Yuhanna IS, Girardi G, Herz J, Urbanus RT, de Groot PG, Thorpe PE, Salmon JE, Shaul PW, Mineo C. Antiphospholipid antibodies promote leukocyte-endothelial cell adhesion and thrombosis in mice by antagonizing eNOS via beta2GPI and apoER2. J Clin Invest. 2011;121(1):120-131.  PubMed, PubMedCentral, CrossRef
  14. Staub HL, Bertolaccini ML, Khamashta MA. Anti-phosphatidylethanolamine antibody, thromboembolic events and the antiphospholipid syndrome. Autoimmun Rev. 2012;12(2):230-234. PubMed, CrossRef
  15. Velásquez M, Rojas M, Abrahams VM, Escudero C, Cadavid AP. Mechanisms of Endothelial Dysfunction in Antiphospholipid Syndrome: Association With Clinical Manifestations. Front Physiol. 2018;9:1840. PubMed, PubMedCentral, CrossRef
  16. Wijetilleka S, Scoble T, Khamashta M. Novel insights into pathogenesis, diagnosis and treatment of antiphospholipid syndrome. Curr Opin Rheumatol. 2012;24(5):473-81. PubMed, CrossRef
  17. Cella M, Farina MG, Dominguez Rubio AP, Di Girolamo G, Ribeiro ML, Franchi AM. Dual effect of nitric oxide on uterine prostaglandin synthesis in a murine model of preterm labour. Br J Pharmacol. 2010;161(4):844-855. PubMed, PubMedCentral, CrossRef
  18. Ferreira EI, Serafim RAM. Nitric Oxide Synthase Inhibitors. Nitric Oxide Synthase – Simple Enzyme-Complex Roles. (May 17th 2017). Available at https://www.intechopen.com/books/nitric-oxide-synthase-simple-enzyme-complex-roles/nitric-oxide-synthase-inhibitor
    CrossRef
  19. Everett TR, Wilkinson IB, Lees CC. Drug development in preeclampsia: a ‘no go’ area? J Matern Fetal Neonatal Med. 2012;25(1):50-52.  PubMed, CrossRef
  20. Moore C, Tymvios C, Emerson M. Functional regulation of vascular and platelet activity during thrombosis by nitric oxide and endothelial nitric oxide synthase. Thromb Haemost. 2010;104(2):342-349.  PubMed, CrossRef
  21. Napoli C, Ignarro LJ. Nitric oxide and pathogenic mechanisms involved in the development of vascular diseases. Arch Pharm Res. 2009;32(8):1103-1108. PubMed, CrossRef
  22. Danylovych HV., Danylovych YuV, Bohach TV, Hurska VT, Kosterin SO. Sources and regulation of nitric oxide synthesis in uterus smooth muscle cells. Ukr Biochem J. 2019; 91(4):33-40. CrossRef
  23. Lopez-Pedrera Ch, Barbarroja N, Jimenez-Gomez Y, Eduardo Collantes-Estevez E, Aguirre MA, Cuadrado MJ. Oxidative stress in the pathogenesis of atherothrombosis associated with antiphospholipid syndrome and systemic lupus erythematosus: new therapeutic approaches. Rheumatology (Oxford). 2016;55(12):2096-2108. PubMed,  CrossRef
  24. Zaichenko HV, Lar’ianovska YuB, Deieva TV. Morphological status of uterus and placenta in experimental model of antiphospholipid syndrome in mice. Ukr Med Almanac. 2011;14(4):136-141. (In Ukrainian).
  25. Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR. Analisis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem. 1982;126(1):131-138. PubMed, CrossRef
  26. Kiselyk IO, Lutsyk MD, Shevchenko LYu. Features of determination of nitrates and nitrites in blood of patients with viral hepatitis and jaundice of other etiology. Lab Diagnost. 2001;(3):43-45. (In Ukrainian).
  27. Giannella L, Beraldi R, Giulini S, Cerami LB, Mfuta K, Facchinetti F. Nitric oxide metabolite levels and assessment of cervical length in the prediction of preterm delivery among women undergoing symptomatic preterm labor. Int J Gynaecol Obstet. 2012;116(3):223-227. PubMed, CrossRef
  28. Chighizola CB,  Ubiali T,  Meroni PL. Treatment of Thrombotic Antiphospholipid Syndrome: The Rationale of Current Management – An Insight into Future Approaches. J Immunol Res. 2015;2015:951424. PubMed, PubMedCentral, CrossRef
  29. Krynytska IYa, Marushchak MI. The indices of nitrogen (II ) oxide system in experimental hepatopulmonary syndrome. Ukr Biochem J. 2018; 90(5):91-97.
    CrossRef
  30. Salim T, Sershen CL, May EE. Investigating the Role of TNF-α and IFN-γ Activation on the Dynamics of iNOS Gene Expression in LPS Stimulated Macrophages. PLoS ONE. 2016;11(6):e0153289. PubMed, PubMedCentral, CrossRef
  31. Manda-Handzlik  A, Bystrzycka W, Cieloch A, Glodkowska-Mrowka E, Jankowska-Steifer E, Heropolitanska-Pliszka E, Skrobot A, Muchowicz A, Ciepiela O, Wachowska M, Demkow U. Nitric oxide and peroxynitrite trigger and enhance release of neutrophil extracellular traps. Cell Mol Life Sci. 2019: 1-17. PubMed, CrossRef
  32. Mineo C. Inhibition of nitric oxide and antiphospholipid antibody-mediated thrombosis. Curr Rheumatol Rep. 2013;15(5):324. PubMed, PubMedCentral, CrossRef
  33. Wiest R, Groszmann RJ. The paradox of nitric oxide in cirrhosis and portal hypertension: too much, not enough. Hepatology. 2002;35(2):478-491. PubMed, CrossRef
  34. Heusch P, Aker S, Boengler K, Deindl E, van de Sand A, Klein K, Rassaf T, Konietzka I, Sewell A, Menazza S, Canton M, Heusch G, Di Lisa F, Schulz R. Increased inducible nitric oxide synthase and arginase II expression in heart failure: no net nitrite/nitrate production and protein S–nitrosylation. Am J Physiol Heart Circ Physiol. 2010;299(2):H446-53.  PubMed, CrossRef
  35. Mukherjee P, Cinelli MA, Kang S, Silverman RB. Development of nitric oxide synthase inhibitors for neurodegeneration and neuropathic pain. Chem Soc Rev. 2014;43(19):6814–6838. PubMed, PubMedCentral, CrossRef
  36. Genç H, Baysal B, Eren B, Yılmaz BD. The Protective Effect of Amino-guanidine, an Inducible Nitric Oxide Synthase Inhibitor, on Aluminium Sulphate Neuro-toxicity in the Rat (Wistar albino) Cerebellar Purkinje Cells: Stereological Study. Middle Black Sea J Health Sci. 2017;3(3):7-14. CrossRef
  37. Rytlewski K, Olszanecki R, Lauterbach R, Grzyb A, Kiec-Wilk B, Dembinska-Kiec A, Basta A. Effects of oral L-arginine on the pulsatility indices of umbilical artery and middle cerebral artery in preterm labor. Eur J Obstet Gynecol Reprod Biol. 2008;138(1):23-28. PubMed, CrossRef
  38. Tiboni GM, Del Corso A, Marotta F. Progestational agents prevent preterm birth induced by a nitric oxide synthesis inhibitor in the mouse. In vivo. 2008;22(4):447-450. PubMed
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