Effect of L-arginine and aminoguanidine on the cytokine profile in obstetric antiphospholipid syndrome

Keywords: nitric oxide; interleukins; pregnancy; mice.

Abstract

Antiphospholipid syndrome (APS) is one of the autoimmune causes of miscarriage in pregnancy. We researched the influence of L-arginine (25 mg/kg), the precursor of nitric oxide synthesis, and aminoguanidine, the inhibitor of inducible NO-synthase (10 mg/kg) on the concentration of IL-1β, IL-6, TNF-α, IL-4, IL-10 in serum of BALB/c mice on the 18th day of pregnancy in cases of APS. In the serum of the pregnant mice with APS, an increase in the concentration of proinflammatory cytokines (IL-1β, IL-6, TNF-α) and a decrease in the concentration of anti-inflammatory cytokines (IL-4 and IL-10) was evidenced, relative to those of the pregnant animals without APS. With the use of L-arginine, a decrease in the concentration of IL-1β, IL-6, TNF-α and an increase in the concentration of IL-4 and IL-10 was established, compared with the indicators of the pregnant mice with APS. The introduction of aminoguanidine, the selective inhibitor of iNOS, did not cause any changes in IL-1β, IL-6 and IL-10 compared with the group of animals with APS. However, a decrease in TNF-α concentration and an increase in IL-4 concentration were proved in this series compared with the group of pregnant animals with APS. Combined administration of L-arginine and aminoguanidine caused a decrease in the concentration of IL-1β, IL-6, TNF-α and an increase in the concentration of IL-4 and IL-10, compared with the indicators of the animals with APS. Thus, the combined administration of L-arginine and aminoguanidine to the pregnant mice with APS contributes to the rebalancing of proinflammatory and anti-inflammatory cytokines in the serum more than their individual use.

References

Abrahams, V. M., Chamley, L. W., & Salmon, J. E. (2017). Emerging treatment models in rheumatology: Antiphospholipid syndrome and pregnancy: Pathogenesis to translation. Arthritis Rheumatology, 69(9), 1710–1721.

Aljameil, N., Tabassum, H., AlMayouf, H, Alshenefy, A., Almohizea, M. M., & Ali, M. N. (2018). Identification of serum cytokines as markers in women with recurrent pregnancy loss or miscarriage using MILLIPLEX analysis. Biomedical Research, 29, 3512–3517.

Ames, P. R. J., Batuca, J. R., Ciampa, A., Ccone, L. І., & Alves, J. D. (2010). Clinical relevance of nitric oxide metabolites and nitrative stress in thrombotic primary antiphospholipid syndrome. The Journal of Rheumatology, 37(12), 2523–2530.

Bicadze, V. O., Hizroeva, D. H., Idrisova, L. J., Abramjan, R. R., Andreeva, M. D., & Makacarija, A. D. (2015). Katastroficheskij antifosfolipidnyj sindrom [Cata­strophic antiphospholipid syndrome]. Voprosy Patogeneza. Akusherstvo, Ginekologija i Reprodukcija, 2, 32–53 (in Russian).

Brann, E., Edvinsson, A., Rostedt Punga, A., Sundström-Poromaa, I., & Skalkidou, A. (2019). Inflammatory and anti-inflammatory markers in plasma: From late pregnancy to early postpartum. Scientific Reports, 9, 1863.

Chighizola, C. B., & Jesus, G. R. (2014). Antiphospholipid antibodies and infertility. Lupus, 23, 1232–1238.

Gomez-Puerta, J. A., & Cervera, R. (2014). Diagnosis and classification of the antiphospholipid syndrome. Journal of Autoimmunity, 48–49, 20–25.

Kiseleva, A. V., Churliaev, I. A., & Grigorev, E. V. (2019). Rol’ oksida azota v povrezhdenii neironov pri kriticheskikh sostoianiiakh [The role of nitric oxi­de in damage to neurons in critical conditions]. Obshchaia Reanimatologiia, 5, 80–84 (in Russian).

Lopez-Pedrera, C., Barbarroja, N., & Jimenez-Gomez, Y. (2016). Oxidative stress in the pathogenesis of atherothrombosis associated with antiphospholipid syndrome and systemic lupus erythematosus: New therapeutic approaches. Rheumatology, 55, 2096–2108.

Makatsariia, A. D., Bitsadze, V. O., & Khizroeva, D. K. (2012). Katastroficheskiy antifosfolipidnyy sindrom v akusherskoy praktike [Catastrophic antiphospholipid syndrome in obstetric practice]. Zhurnal Akusherstva i Zhenskikh Bolezney, 3, 7–21 (in Russian).

Ostapchenko, L. I., Synelnyk, T. B., Rybalchenko, T. V., & Rybalchenko, V. K. (2010). Biokhimichni mekhanizmy apoptozu [Biochemical mechanisms of apoptosis]. Kyiv University, Kyiv (in Ukrainian).

Posokhova, K. A., Sampara, S. R., & Sak, I. Y. (2013). Vplyv tivortinu na perebih vahitnosti, stan plodiv ta novonarodzhenykh pry eksperymentalnomu antyfosfolipidnomu syndromi [Effect of tivortin on pregnancy, fetal and newborn status in experimental antiphospholipid syndrome]. Medychna Khimiia, 15(4), 26–29 (in Ukrainian).

Rahman, A. (2016). Antiphospholipid syndrome in pregnancy. Indian Journal of Rheumatology, 11, 117–121.

Saha, S., Mundia, M. M., Zhang, F., Demers, R. W., Korobova, F., Svitkina, T., Pe­rieteanu, A. A., Dawson, J. F., & Kashina, A. (2010). Arginylation regulates intracellular actin polymer level by modulating actin properties and binding of capping and severing proteins. Molecular Biology of the Cell, 21, 1350–1361.

Salim, T., Sershen, C. L., & May, E. E. (2016). Investigating the role of TNF-α and IFN-γ activation on the dynamics of iNOS gene expression in LPS stimulated macrophages. PLoS One, 11(6), e0153289.

Shchuruk, N. V. (2018). Osoblyvosti balansu tsytokiniv u zhinok iz reproduktyv­nymy vtratamy v anamnezi v dynamitsi uskladnenoji i neuskladnenoji vahitnosti [Features of cytokine balance in women with a history of reproductive loss in the dynamics of complicated and uncomplicated pregnancy]. Aku­sherstvo ta Hinekolohiia, 1, 132–136 (in Ukrainian).

Shejbak, V. M., & Pavljukovec, A. J. (2013). Arginin i immunnaja sistema – vozmozhnye mehanizmy vzaimodejstvija [Arginine and the immune system are possible interaction mechanisms]. Vestnik Vitebskogo Gosudarstvennogo Me­dicinskogo Universiteta, 12(1), 6–13 (in Russian).

Sulagna, D., & Pallav, S. (2017). Defining pregnancy phases with cytokine shift. Journal of Pregnancy and Reproduction, 1(4), 1–3.

Tang, K. T., Hsieh, T. Y., Chao, Y. H., Li, J. P., Lan, J. L., Lin, C. C., & Chen, D. Y. (2019). Apoptosis in patients with primary antiphospholipid antibody syndro­me. International Journal of Rheumatic Diseases, 22(4), 677–685.

Ventskivska, I. B., Bila, V. A., & Zahorodnia, O. S. (2011). Rol’ prykhovanykh trombofilichnykh staniv v patohenezi zahrozy peredchasnykh polohiv [The role of latent thrombophilic conditions in the pathogenesis of the threat of preterm birth]. Zdorove Zhenshchyn, 58, 173–176 (in Ukrainian).

Zaichenko, H. V., Lar’ianovska, I. B., & Deieva, T. V. (2011). Morfolohichnyi stan matky ta platsenty pry eksperymental’nomu modeliuvanni hestatsiinoho antyfosfolipidnoho syndromu na myshakh [Morphological state of the uterus and placenta in experimental modeling of gestational antiphospholipid syndrome in mice]. Ukrainskyi Medychnyi Almanakh, 14(4), 136–141 (in Ukrainian).

Zhang, G. L., Wang, Y. H., Teng, H. L., & Lin, Z. B. (2001). Effects of aminoguanidine on nitric oxide production induced by inflammatory cytokines and endotoxin in cultured rat hepatocytes. World Journal of Gastroenterology, 7(3), 331–334.

Published
2020-02-13
How to Cite
Yaremchuk, O. Z., Posokhova, K. A., Lykhatskyi, P. H., Letniak, N. Y., & Moseychuk, I. P. (2020). Effect of L-arginine and aminoguanidine on the cytokine profile in obstetric antiphospholipid syndrome . Regulatory Mechanisms in Biosystems, 11(1), 123-126. https://doi.org/10.15421/022018