Yaremchuk O. Z.

INFLUENCE OF L-ARGININE AND AMINOGUANIDINE ON THE CASPASE-3 AND β-ACTIN CONTENT IN EXPERIMENTAL PREGNANT MOUSE MODEL WITH ANTIPHOSPHOLIPID SYNDROME


About the author:

Yaremchuk O. Z.

Heading:

CLINICAL AND EXPERIMENTAL MEDICINE

Type of article:

Scentific article

Annotation:

Research purpose. Antiphospholipid syndrome (APS) is an autoimmune disease that is characterized by arterial or venous thrombosis, miscarriage, thrombocytopenia. APS is one of the autoimmune causes of pregnancy miscarriage. The purpose of our study was to evaluate the effect of L-arginine and aminoguanidine on caspase-3 and β-actin content in the liver of BALB/c mice on day 18 of pregnancy under APS. Object and research methods. The experimental animals were divided into 5 groups: the 1st – control; the 2nd – animals with experimental APS, the 3rd – animals with APS and administration of L-arginine hydrochloride (Larginine) (25 mg/kg), the 4th – animals with APS and administration of aminoguanidine (10 mg/kg), the 5th – animals with APS administered L-arginine together with aminoguanidine. L-arginine and aminoguanidine were administered intraperitoneally once a day, on a daily basis for 10 days before fertilization and for 17 days during pregnancy. After APS confirmation (day 10), the females of all groups were mated with the males. The animals were removed from the experiment on the 18th day of pregnancy. The content of caspase-3 and β-actin in liver tissue was determined by Western blot analysis. Research results and their discussion. Caspase-3 content in the liver increased 2.9-fold, while β-actin increased 1.8-fold, compared to control. One of the regulators of apoptosis and a molecular mediator between the two types of cell death is nitric oxide (NO). Violation of the NO bioavailability during APS can be associated with a decrease in the concentration of substrate (L-arginine), as well as with the increase in the formation of superoxide-anion, which quickly binds and inactivates NO with the formation of toxic peroxynitrite. L-arginine supplementation decreased caspase-3 content by 44%, β-actin content by 10%, comparing with the values obtained from pregnant mice with APS. The introduction of aminoguanidine was not accompanied by changes in β-actin content, compared with the group of animals with APS. However, there was a 63% reduction in caspase-3 content in aminoguanidine group comparing to the APS animal group. Combined administration of L-arginine and aminoguanidine in the liver revealed a decrease in caspase-3 content by 77% and β-actin by 29%, compared to the values from animals with APS. Additionally, combined supplementation with L-arginine and aminoguanidine caused a more profound decrease in the content of caspase-3 and β-actin in the liver relatively to the indices of groups of animals that were administered L-arginine and aminoguanidine separately. Conclusion. Thus, the combined administration of L-arginine, the precursor for the synthesis of NO, and an inhibitor of inducible NOS, aminoguanidine, in pregnant APS mice had more profound effect than their individual use, as related to restoration of caspase-3 and β-actin content in the liver

Tags:

antiphospholipid syndrome, pregnancy, nitric oxide, apoptosis.

Bibliography:

  1. Shchuruk NV. Osoblyvosti balansu tsytokiniv u zhinok iz reproduktyvnymy vtratamy v anamnezi v dynamitsi uskladnenoi i neuskladnenoi vahitnosti. Akusherstvo ta hinekolohiia. 2018;1:132-6. [in Ukrainian].
  2. Chighizola CB, Jesus GR. Antiphospholipid antibodies and infertility. Lupus. 2014;23:1232-8.
  3. Tang KT, Hsieh TY, Chao YH, Li JP, Lan JL, Lin CC, Chen DY. Apoptosis in patients with primary antiphospholipid antibody syndrome. Int J Rheum Dis. 2019;22(4):677-85. DOI: 10.1111/1756-185X.13468
  4. Ostapchenko LI, Synelnyk TB, Rybalchenko TV, Rybalchenko VK. Biokhimichni mekhanizmy apoptozu. Navchalnyi posibnyk. 2010. 314 s. [in Ukrainian].
  5. Ames PRJ, Batuca JR, Ciampa A, Ccone LІ, Alves JD. Clinical Relevance of Nitric Oxide Metabolites and Nitrative Stress in Thrombotic Primary Antiphospholipid Syndrome. The Journal of Rheumatology. 2010;37(12):2523-30. DOI: 10.3899/jrheum.100494C1
  6. Kiseleva AV, Churliaev IuA, Grigorev EV. Rol oksida azota v povrezhdenii neironov pri kriticheskikh sostoianiiakh. Obshchaia reanimatologiia. 2019;5:80-4. DOI: 10.15360/1813-9779-2009-5-80 [in Russian].
  7. Popov SS, Pashkov AN, Agarkov AA, Shulgin KK. Intensivnost protcessov apoptoza, aktivnost akonitatgidratazy i uroven tcitrata u patcientov s sakharnym diabetom 2 tipa, oslozhnennym steatogepatitom, pri primenenii epifamina na fone bazisnogo lecheniia. Biomeditcinskaia khimiia. 2015;61(3):400-6. DOI: 10.18097/PBMC20156103400 [in Russian].
  8. Zaichenko HV, Lar’ianovska IuB, Deieva TV. Morfolohichnyi stan matky ta platsenty pry eksperymentalnomu modeliuvanni hestatsiinoho antyfosfolipidnoho syndromu na myshakh. Ukrainskyi medychnyi almanakh. 2011;14(4):136-41. [in Ukrainian].
  9. Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc. Natl. Acad. Sci. USA. 1979;76(9):4350-4.
  10. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 1976;72:248-54.
  11. Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970;227(5259):680-5.
  12. Marushchak M, Krynytska I, Milevska L, Miz A, Mialiuk O. The changes of activity of effector caspase cascade components in case of alimentary obesity in rats. Bangladesh Journal of Medical Science. 2017;16(2):252-8.
  13. Lopez-Pedrera Ch, Barbarroja N, Jimenez-Gomez Y. Oxidative stress in the pathogenesis of atherothrombosis associated with antiphospholipid syndrome and systemic lupus erythematosus: new therapeutic approaches. Rheumatology. 2016;55:2096-108.
  14. Chen H, Leng Y, Li Z. Beta-actin in the signaling of transmembrane TNF-alfa-mediated cytotoxicity. Methods Mol Biol. 2014;1155:55-68.
  15. Xie X, Venit T, Drou N, Percipalle P. In mitochondria actin regulates mtDNA transcription and is required for mitochondrial quality control. iScience. 2018;25(3):226-37.
  16. Saha S, Mundia MM, Zhang F, Demers RW, Korobova F, Svitkina T, et al. Arginylation regulates intracellular actin polymer level by modulating actin properties and binding of capping and severing proteins. Molecular Biology of the Cell. 2010;21:1350-61.
  17. Dingman A, Lee SY, Derugin N, Wendland MF, Vexler ZS. Aminoguanidine inhibits caspase-3 and calpain activation without affecting microglial activation following neonatal transient cerebral ischemia. Journal of Neurochemistry. 2006;96:1467-79.

Publication of the article:

«Bulletin of problems biology and medicine» Issue 1 (155), 2020 year, 215-218 pages, index UDK 547.495.9:546.172.6-06:616.36-002.43:618.3:616-005.6]-092.9

DOI: