MORPHOLOGICAL CHANGES IN THE KIDNEY IN EXPERIMENTAL ANTIPHOSPHOLIPID SYNDROME: EFFECTS OF NITRIC OXIDE SYNTHESIS MODULATORS
DOI:
https://doi.org/10.11603/1811-2471.2020.v.i1.11088Keywords:
antiphospholipid syndrome, kidney, L-arginine, aminoguanidineAbstract
The kidneys are one of the main target organs in all clinical forms of antiphospholipid syndrome (APS).
The aim – to assess the effect of L-arginine, the precursor of nitric oxide synthesis, and NO synthase, the inhibitor of inducible aminoguanidine, on morphofunctional changes in the kidneys in experimental APS.
Material and Methods. The BALB/c female mice modeled with APS were used in the study. L-arginine (25 mg/kg) and aminoguanidine (10 mg/kg) were used for correction. The sampling of the material for microscopic examination was performed according to conventional methods. Kidney tissue samples were stained with hematoxylin and eosin.
Results and Discussion. Microscopic studies of the kidneys of the animals with APS revealed destructive changes in all components and impaired cerebral and circulatory organ flow. Histologic changes of kidneys of the animals modeled with APS, which were administered with L-arginine, were manifested by a decrease in blood supply of organ vessels maintaining the integrity of vascular wall. Microscopic changes of kidneys of the animals with APS administered with aminoguanidine were manifested by enlargement and blood filling of many vessels of predominantly small arteries of the cortical substance.
With the introduction of L-arginine and aminoguanidine, a relative normalization of the vascular component of the organ was revealed in the kidneys of the animals with APS; only the interparticle and interstitial veins were blood filled.
Conclusions. Vascular disorders occur in the kidney in cases of APS that cause significant destructive changes of the nephrons. The application of modulators of nitric oxide synthesis (L-arginine and aminoguanidine), separately and especially when combined, leads to reduction of pathological changes in nephron components in the presence of APS in the BALB/c mice.
References
Granakopoulos, B., & Krilis, S. (2013). The pathogenesis of the antiphospholipid syndrome. The New England Journal of Medicine, 368, 1033-1044. DOI: https://doi.org/10.1056/NEJMra1112830
Kozlovskaya, N.L. (2006). Sosudistoye porazheniye pochek pri antifosfolipidnom sindrome (Obzor literatury) [Vascular damage to the kidneys with antiphospholipid syndrome (review)]. Nefrologiya i dializ – Nephrology and Dialysis, 8(3), 206-216 [in Russian].
Tektonidou, M.G., Sotsiou, F., & Moutsopoulos, H.M. (2008). Antiphospholipid syndrome (APS) nephropathy in catastrophic, primary, and systemic lupus erythematosus-related APS. J. Rheumatol., 35 (10), 1983-1988.
Nasonov, E.L. Antyfosfolipydnyy syndrom [Antiphospholipid syndrome]. Moscow: Litterra [in Russian].
Velásquez, 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 DOI: https://doi.org/10.3389/fphys.2018.01840
Piliponova, V.V., & Slobodianiuk, V.A. (2019). Rol endotelialnoi dysfunktsii nyrok v patohenezi zakhvoriuvan ta yikh uskladnen (Ohliad literatury) [The role of endothelial dysfunction in the pathogenesis of diseases and their complications (Review)]. Zdobutky klinichnoi i eksperymentalnoi medytsyny – Achievements of Clinical and Experimental Medicine, 3, 32-38. doi 10.11603/1811-2471.2019.v.i3.10503 [in Ukrainian].
Ames, P.R., Batuca, J.R., Ciampa, A., Iannaccone, L., & Alves, J.D. (2010). Clinical relevance of nitric oxide metabolites and nitrative stress in thrombotic primary antiphospholipid syndrome. J. Rheumatol., 37 (12), 2523-2530. DOI: https://doi.org/10.3899/jrheum.100494
Wijetilleka, S., Scoble, T., & Khamashta, M. (2012). Novel insights into pathogenesis, diagnosis and treatment of antiphospholipid syndrome. Curr. Opin. Rheumatol., 24 (5), 473-481. DOI: https://doi.org/10.1097/BOR.0b013e328354ae8c
Cella, M., Farina, M.G., Dominguez, A.P., Girolamo, R.D., Ribeiro, M.L., & Franchi, A.M. (2010). Dual effect of nitric oxide on uterine prostaglandin synthesis in a murine model of preterm labour. Br. J. Pharmacol., 161 (4), 844-855. DOI: https://doi.org/10.1111/j.1476-5381.2010.00911.x
Golovach, I.Yu., Yegudina, Ye.D., & Rekalov, D.G. (2019). Porazheniye pochek na fone antifosfolipidnogo sindroma [Kidney damage on the background of antiphospholipid syndrome]. Pochki – Kidneys, 8 (3), 161-173. doi: 10.22141/2307-1257.8.3.2019.176455 [in Russian]. DOI: https://doi.org/10.22141/2307-1257.8.3.2019.176455
Ostryakova, Ye.V., Patrushev, L.I., & Reshetnyak, T.M. (2011). Antifosfolipidnyy sindrom i sistema fibrinoliza [Antiphospholipid syndrome and fibrinolysis system]. Nauchno-prakticheskaya revmatologiya – Scientific and Practical Rheumatology, 6, 57-64 [in Russian].
Krone, K.A., Allen, K.L., & McCrae, K.R. (2010). Impaired fibrinolysis in the antiphospholipid syndrome. Curr. Rheumatol. Rep., 12 (1), 53-57. DOI: https://doi.org/10.1007/s11926-009-0075-4
McDonnell, T., Wincup, C., Buchholz, I., Pericleousc, C., Giles, I., & Ripoll, V. (2019). The role of beta-2-glycoprotein I in health and disease associating structure with function: more than just APS. Blood Reviews, 33, 100610.
Gao, R., Yu, W., Wen, Y., & Li, H. (2016) Beta2-glycoprotein I expression in lupus nephritis patients with antiphospholipid-associated nephropathy. J. Rheumatol., 43, 2026-2032.
Zaichenko, H.V., Larianovska, Yu.B., Deieva, T.V., Shevchenko, O.I., Starokozhko, V.Yu., Kudina, O.V., & Sak, I. Yu. (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].
Horalskyi, L.P., Khomych, V.Т., & Kononskyi, О.І. (2011). Osnovy histolohichnoi tekhniky i morfofunktsionalni metody doslidzhen u normi ta pry patolohii [Fundamentals of histological technique and morphofunctional methods of research in norm and in pathology]. Zhytomyr: Polissia [in Ukrainian].
Zheng, H., Chen, Y., Ao, W., Yan, Shen, Xiao-Wei, Chen, Min, Dai, Xiao-dong, Wang, Yu-Cheng, Yan & Cheng-de, Yang (2009). Antiphospholipid antibody profiles in lupus nephritis with glomerular microthrombosis: a prospective study of 124 cases. Arthritis Res. Ther., 11 (3), 93. doi: 10.1186/ar2736 DOI: https://doi.org/10.1186/ar2736
Gerhardsson, J., Sundelin, B., Zickert, A., Padyukov, L., Svenungsson, E., & Gunnarsson, I. (2015). Histological antiphospholipid-associated nephropathy versus lupus nephritis in patients with systemic lupus erythematosus: an observational cross-sectional study with longitudinal follow-up. Arthritis Res. Ther., 17, 109. doi: 10.1186/s13075-015-0614-5 DOI: https://doi.org/10.1186/s13075-015-0614-5
de Azevedo, F.V.A., Maia, D.G., de Carvalho, J.F., & Rodrigues C.E.M. (2018). Renal involvement in antiphospholipid syndrome. Rheumatol. Int., 38 (10), 1777-1789. doi: 10.1007/s00296-018-4040-2 DOI: https://doi.org/10.1007/s00296-018-4040-2
Smyth, A., Oliveira, G.H., Lahr, B.D., Bailey, K.R., Norby, S.M., & Garovic, V.D. (2010). A systematic review and meta-analysis of pregnancy outcomes in patients with systemic lupus erythematosus and lupus nephritis. Clin. J. Am. Soc. Nephrol., 5 (11), 2060-2068. doi: 10.2215/CJN.00240110 DOI: https://doi.org/10.2215/CJN.00240110
