INFLUENCE OF L-ARGININE AND AMINOGUANIDIN ON THE LEVEL OF SYNTHESIS OF NITRIC OXIDE IN THE CEREBELLUM AND CEREBRAL HEMISPHERES IN EXPERIMENTAL ANTIPHOSPHOLIPID SYNDROME

Authors

  • O. Z. Yaremchuk I. HORBACHEVSKY TERNOPIL NATIONAL MEDICAL UNIVERSITY
  • K. A. Posokhova I. HORBACHEVSKY TERNOPIL NATIONAL MEDICAL UNIVERSITY
  • I. P. Kuzmak I. HORBACHEVSKY TERNOPIL NATIONAL MEDICAL UNIVERSITY

DOI:

https://doi.org/10.11603/mcch.2410-681X.2019.v.i4.10696

Keywords:

antiphospholipid syndrome, pregnancy, nitric oxide, cerebellum, cerebral hemispheres

Abstract

Introduction. Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the presence of antiphospholipid antibodies, arterial and venous thrombosis, thrombocytopenia, miscarriage.

The aim of the study – to investigate the effect of the combined effect of L-arginine and aminoguanidine on the content of nitrite anions (NO2) and nitrate anions (NO3) in the cerebellum and cerebral hemispheres of BALB/c mice with APS before pregnancy and on the 18th day of pregnancy.

Research Methods. The study was performed on female BALB/c mice, for which APS was simulated. L-arginine (25 mg/kg) in combination with aminoguanidine (10 mg/kg) was used for correction. The content of NO in the homogenates of cerebellum and cerebral hemispheres of the animals with APS before pregnancy and on the 18th day of pregnancy was determined by the number of its stable metabolites of nitrite anions (NO2) and nitrate anions (NO3).

Results and Discussion. The content of stable metabolites of nitric oxide NO2 and NO3 in the cerebellum and cerebral hemispheres increased in the BALB/c mice with APS compare to the intact animals. In cases of experimental APS, on the 18th day of pregnancy, an increase in the content of NO2 and NO3 in the cerebellum was evidenced, as well as a decrease in NO2 and NO3 in the brain hemispheres of the animals with APS compare to the controls. In case of the combined administration of precursor of synthesis of NO L-arginine and a selective inhibitor of iNOS aminoguanidine into the animals with APS, a decrease in the content of NO2 and NO3 in the cerebellum (by 28 % and 17 %) and cerebral hemispheres (by 16 % and 10 %) was evidenced comparing to the animals with APS. In the pregnant BALB/c mice with APS administered with L-arginine in combination with aminoguanidine, a decrease of NO2 by 29 % and NO3 by 25 % in cerebellum, an increase of NO2 by 21 % and NO3by 22 % in the cerebral hemispheres was evidenced comparing to those of the pregnant females with APS.

Conclusions. It has been established that the combined use of the precursor of synthesis of NO L-arginine and a selective inhibitor iNOS aminoguanidine leads to normalization of the level of stable metabolites of NO2 and NO3 nitric oxide synthesis in the cerebellum and cerebral hemispheres of the BALB/c mice with APS before pregnancy and on the 18th day of pregnancy.

References

Vasilyev, D.V., Chernobay, L.V., & Vasilyeva, O.V. (2019). Antifosfolipidnyy sindrom: klinika i genetika tromboticheskikh proiavleniy [Antiphospholipid syndrome: clinic and genetics of thrombotic manifestations]. Ukrainskyi zhurnal medytsyny, bіolohіi ta sportu – Ukrainian Journal of Medicine, Biology and Sport, 2 (4), 161-167 [in Russian].

Yaremchuk, O.Z., Posokhova, K.A., Bryk, A.R., Kulitska, M.I., Kuzmak, I.P., & Mehno, N.Ya. (2017). Pokaznyky prooksydantno-antyoksydantnoi systemy pechinky pry eksperymentalnomu antyfosfolipidnomu syndromi ta zastosuvanni L-arhininu [Parameters of liver prooxidative-antioxidant system in cases of experimental antiphospholipid syndrome and L-arginin administration]. Medychna ta klinichna khimiia – Medical and Clinical Chemistry, 19 (3), 63-70 [in Ukrainian].

Ulyanova, O.V., Kutashov, V. A., & Khabaro­va, T.Yu. (2016). Osobennosti nevrologicheskikh proyav­leniy u patsientov s antifosfolipidnym sindromom [Featu­­res of neurological manifestations in patients with anti­phos­pholipid syndrome]. Vestnik KazNMU – Bulletin of KazNMU, 2, 333-338 [in Russian].

Yaremchuk, О.Z., Posokhova, K.A., & Kulitska, M.I. (2018). Vplyv L-arhininu ta aminohuanidynu na pokaznyky vilnoradykalnoho okysnennia u nyrkakh pry ekspery­mentalnomu antyfosfolipidnomu syndromi [Influence of L-arginin and aminoguanidine on renal free-radical oxidation rates in cases of experimental antiphospolipid syndrome]. Svit medytsyny ta biolohii – World of Medicine and Biology, 3 (65), 210-214 [in Ukrainian].

Kalashnikova, L.A., & Dzhamantaeva, B.D. (2015). Antifosfolipidnyy sindrom s nevrologicheskimi proyav­leniyami, imitiruyushchimi rasseyannyy skleroz [Antiphos­pholipid syndrome with neurological manifestations that mimic multiple sclerosis]. Neirokhirurgiya i nevrologiya Kazakhstana – Neurosurgery and Neurology of Kazakh­stan, 1 (38), 15-23 [in Russian].

Etemadifar, M., Dehghani, L., Tahani, S., Toghia­nifar, N., Rahaimi, M., & Eskandari, N. (2013). Neurological manifestations in patients with antiphospholipid syndrome. Iran J. Neurol., 12 (4), 172-175.

Ahluwalia, J., & Sreedharanunni, S. (2017). The Laboratory diagnosis of the antiphospholipid syndrome. Indian J. Hematol. Blood Transfus., 33 (1), 8-14. doi: 10.1007/s12288-016-0739-y

D’Angelo, C., Franch, O., Fernández-Paredes, L., Oreja-Guevara, C., Núñez-Beltrán, M., Comins-Boo, A., … Sanchez-Ramon S. (2019). Antiphospholipid anti­bodies overlapping in isolated neurological syndrome and multiple sclerosis: neurobiological insights and diagnostic challenges. Front. Cell. Neurosci, 13, 107. doi: 10.3389/fncel.2019.00107

McDonnell, T., Wincup, C., Buchholz, I., Peri­cleous, C., Giles, I., Ripoll, V., ...Rahman, A. (2019). The role of beta-2-glycoprotein I in health and disease associating structure with function: more than just APS. Blood Reviews., 33, 100610 doi:10.1016/j.blre.2019. 100610

Posokhova, K.A., Sak, I.Yu., & Sampara, S.R. (2014). Akusherskyi antyfosfolipidnyi syndrom i systema oksydu azotu (ohliad literatury i rezultaty vlasnykh do­slidzhen) [Obstetric antiphospholipid syndrome and system of nitric oxide (review and results of own re­search)]. Medychna khimiia – Medical Chemistry, 16 (1), 73-80 [in Ukrainian].

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. doi:10.3899/jrheum.100494C1.

Lopez-Pedrera, Ch., Barbarroja, N., Jimenez-Gomez, Y., Collantes-Estevez, E., Aguirre, M.A., & Cuad­rado, M.J. (2016). Oxidative stress in the pathogenesis of atherothrombosis associated with antiphospholipid syndrome and systemic lupus erythematosus: new therapeutic approaches. Rheumatology, 55, 2096-2108. doi: 10.1093/rheumatology/kew054

Alves, J.D., Mason, L.J., & Ames P.R.J. (2005). Antiphospholipid antibodies are associated with enhan­ced oxidative stress, decreased plasma nitric oxide and paraoxonase activity in an experimental mouse model. Rheumatology, 44, 1238-1244. doi: 10.1093/rheuma­tology/keh722

Velasquez, M., Rojas, M., Abrahams, V.M., Escudero, C., & Cadavid, A.P. (2018). Mechanisms of Endothelial Dysfunction in Antiphospholipid Syndrome: Association with Clinical Manifestations. Front. Physiol., 21 (9), 1840. doi: 10.3389/fphys.2018.01840 (2018)

Nasonov, E.L. (2014). Antifosfolipidnyy sindrom [Antiphospholipid syndrome]. Moscow: Litterra [in Russian].

Reutov, V. P., Sorokina, E.G., & Samosudo­va, N.V. (2017). Gemodinamika mozga: glutama­ter­gicheskaya sistema i tsikl oksida azota v regulyatsii mozgovogo krovoobrashcheniya. Novaya kontseptsiya [Brain hemodynamics: glutamatergic system and nitric oxide cycle in the regulation of cerebral circulation. New concept]. Tikhookeanskiy meditsinskiy zhurnal – Pacific Medical Journal, 3, 37-45 [in Russian].

Kurovska, V.O., Pishak, V.P., & Tkachuk, S.S. (2008). Rol oksydu azotu v ishemichnykh i ishemich­noreperfuziinykh ushkodzhenniakh holovnoho mozku [The role of nitric oxide in ischemic and ischemic reper­fusion brain damage]. Bukovynskyi medychnyi visnyk – Bukovyna Medical Bulletin, 12 (4), 143-149 [in Ukrainian].

Zaichenko, H.V., Larianovska, Iu.B., & Deieva, T.V. (2011). Morfolohichnyi stan matky ta platsenty pry eks­perymentalnomu 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 – Ukrainian Medical Almanac, 14 (4), 136-141 [in Ukrainian].

Kamyshnikov, V.S. (2004). Spravochnik po kliniko-biokhimicheskim issledovaniyam i laboratornoy diagnostike [Manual on clinical biochemical research and laboratory diagnostics]. Moscow: MEDpress-inform [in Russian].

Green, L.C., David, A.W., Golawski, J., Skip­per, P.L., Wishnok, J.S., & Tannenbaum, S.R. (1982). Analisis of nitrate, nitrite and [15N] nitrate in biological fluids. Anal. Biochem., 126 (1), 131-138. doi: 10.1016/ 0003-2697(82)90118-x

Kiselyk, I.O., Lutsyk, M.D., & Shevchenko, L.Yu. (2001). Osoblyvosti vyznachennia nitrativ ta nitrytiv u krovi khvorykh na virusni hepatyty ta zhovtianytsi inshoi etiolohii [Features of determination of nitrates and nitrites in blood of patients with viral hepatitis and jaundice of other etiology]. Lab. diahnostyka – Lab. Diagnostics, 3, 43-45 [in Ukrainian].

Ramesh, S., Morrell, C. N., Tarango, C., Tho­mas, G.D., Yuhanna, I.S., Girardi G., … Mineo, Ch. (2011). Antiphospholipid antibodies promote leukocyte-endothelial cell adhesion and thrombosis in mice by antagonizing eNOS via beta2GPI and apoER2. J. Clin. Invest., 121 (1), 120-131. doi: 10.1172/JCI39828.

Maksimovich, N.E. (2003). Poniatie o nitroksi­dergicheskoу sisteme mozga (rol neyronalnykh istoch­nikov) [The concept of the nitroxidergic system of the brain (the role of neuronal sources)]. Zhurnal GGMU – Magazine GSMU, 4, 7-10 [in Russian].

Kiseleva, A.V., Churlyaev, Yu.A., & Grigoryev, E.V. (2019). Rol oksida azota v povrezhdenii neyronov pri kriticheskikh sostoyaniyakh [The role of nitric oxide in damage to neurons in critical conditions]. Obshchaya reanimatologiya – General Resuscitation, 5, 80-84 [in Russian]. doi: 10.15360/1813-9779-2009-5-80

Svenungsson, E., Andersson, M., Brundin, L., van Vollenhoven, R., Khademi, M., Tarkowski, A., ...Olsson, T. (2001). Increased levels of proinflammatory cytokines and nitric oxide metabolites in neuropsychiatric lupus erythematosus. Ann. Rheum. Dis., 60, 372-379. doi: 10.1136/ard.60.4.372

Severyanova, L.A., & Bobyntsev, I.I. (2006). Mekhanizmy deystviya aminokisloty L-arginina na nerv­nuyu i immunnuyu reguliatornye sistemy [The mechanisms of action of the amino acid L-arginine on the nervous and immune regulatory systems]. Kurskiy nauchno-prak­ticheskiy vestnik “Chelovek i ego zdorove” – Kursk Scientific and Practical Bulletin “People and his Health”, 3, 60-75 [in Russian].

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 J. Gastroenterol., 7 (3), 331-334. doi: 10.3748 / wjg.v7.i3.331

Heush, P., Aker, S., Boenger, K., Deindl, E., van de Sand, A., Klein, K., ...Schulz, R. (2010). 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., 299 (2), 446-453. doi: 10.1152/ajpheart.01034.2009

Published

2020-01-30

How to Cite

Yaremchuk, O. Z., Posokhova, K. A., & Kuzmak, I. P. (2020). INFLUENCE OF L-ARGININE AND AMINOGUANIDIN ON THE LEVEL OF SYNTHESIS OF NITRIC OXIDE IN THE CEREBELLUM AND CEREBRAL HEMISPHERES IN EXPERIMENTAL ANTIPHOSPHOLIPID SYNDROME. Medical and Clinical Chemistry, (4), 105–112. https://doi.org/10.11603/mcch.2410-681X.2019.v.i4.10696

Issue

Section

ORIGINAL INVESTIGATIONS