PROOXIDANT-ANTIOXIDANT SYSTEM OF KIDNEYS IN CASE OF EXPERIMENTAL ANTIFOSPHOLIPID SYNDROME AND NITRIC OXIDE SYNTHESIS MODULATORS EFFECT
Introduction. Antiphospholipid syndrome (APS) is one of the most urgent multidisciplinary issues of contemporary medicine. The frequency of kidney damage in cases of APS is 25–78 %.
The aim of the study – to investigate the combined effect of L-arginine and aminoguanidine on the indicators of free radical oxidation and tissue respiration in the kidneys in cases of experimental APS as well as in pregnant animals with this disorder.
Research Methods. The BALB/c female mice with simulated APS were used in the study. L-arginine (25 mg/kg) and aminoguanidine (10 mg/kg) were used for APS correction. The activity and content of antioxidant system components (superoxidedismutase, catalase, reduced glutathione)), the content of lipid hydroperoxides and TBA-reactive substances, the activity of succinatedehydrogenase and cytochromeoxidase in the kidneys of animals with APS were evaluated before pregnancy and on the 18th day of pregnancy.
Results and Discussion. The study results proved that lipid peroxidation processes in the kidneys of BALB/c mice with APS were activated, the prooxidant-antioxidants system was misbalanced. During the research on the 18th day of pregnancy in the kidneys of animals with APS a significant increase in free radical oxidation was revealed, as well as a decrease in the antioxidant enzymes activity and respiratory chain of mitochondria, compare to the control group of pregnant mice. In cases of combined administration of L-arginine and aminoguanidine to the animals with APS, a decrease in the content of TBA-reactive substances by 33 % as well as in superoxidedismutase activity by 15 %, an increase in activity of catalase by 12 %, of succinatedehydrogenase by 16 %, of cytochromeoxidase by 13 % as well as in reduced glutathione content by 23 %, respectively, took place in the animals’ kidneys, compare to the animals with APS only. A combined effect of L-arginine and aminoguanidine caused decreased activity of free-radical oxidation processes as well as activation of antioxidant protection was evidenced in the kidney tissue of the pregnant mice with APS. A significant increase in activity of succinatedehydrogenase by 18 % and cytochromeoxidas by 75 % was proved, compare to the pregnant females with APS.
Conclusions. In experimental APS in the kidney tissue of non-pregnant and pregnant BALB/c mice, the activation of free radical oxidation took place, prooxidant-antioxidant system was misbalanced. In cases of combined administration of L-arginine and aminoguanidine in APS in both groups of animals with APS (pregnant and non-pregnant), the reducing of oxidative stress manifestations.
Tektonidou, M.G., Adrogue, H.E., & Vaidya, S. (2012). Task force report on non-criteria manifestation: nephropathy. Antiphospholipid syndrome: insights and highlights from the 13th International Congress on antiphospholipid antibodies. Erkan, D., & Pierangeli, S. (Ed.). Springer, New York, 207-222.
Golovach, I.Iu., Egudina, E.D., Rekalov, D.G. (2019). Porazhenie pochek na fone antifosfolipidnogo sindroma [Kidney damage on the background of antiphospholipid syndrome]. Kidneys, 8 (3), 161-173. doi: 10.22141/2307-12126.96.36.1999.176455 [in Russian].
Kozlovskaya, N.L., Zakharova, E.V., Zverev, D.V., Sukhanov, A.V., Koen, A., Avdeyeva, O.N., & Epifanova, S.N. (2007). Osobennosti porazheniya pochek, obuslovlennogo sochetaniyem glomerulonefrita i AFS-assotsiirovannoy nefropatii pri sistemnoy krasnoy volchanke (obzor literatury i sobstvennoe nablyudenie) [Features of kidney damage due to a combination of glomerulonephritis and APS-associated nephropathy with systemic lupus erythematosus (review and own observation)]. Nefrologiya i dializ – Nephrology and Dialysis, 9 (4), 439-446 [in Russian].
Azevedo de, 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.
Tektonidou, M.G. (2018). Antiphospholipid syndrome nephropathy: from pathogenesis to treatment. Front. Immunol., 9, 1181-7.
Iuliano, L., Practico, D., & Ferro D. (1997). Enhanced lipid peroxidation in patients positive for antiphospholipid antibodies. Blood, 90 (10), 3931-3935.
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.
Perez-Sanchez, C., Ruiz-Limon, P., & Aguirre, M.A. (2012). Mitochondrial dysfunction in antiphospholipid syndrome: implications in the pathogenesis of the disease and effects of coenzyme Q10 treatment. Blood, 119 (24), 5859-5870.
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.
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.
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].
Gavrilov, V.B., & Mishkorudnaya, M.I. (1983). Spektrofotometricheskoye opredelenie soderzhaniya gidroperekisey lipidov v plazme krovi [Spectrophotometric determination of the content of lipids hydroperoxides in blood plasma]. Lab. delo – Lab. Work, 3, 33-35 [in Russian].
Andreeva, L.I., Kozhemyakin, L.A., & Kishkun, A.A. (1988). Modifikatsiya metoda opredeleniya perekisey lipidov v teste s tiobarbiturovoy kislotoy [Modification of the method for determining lipid peroxides in a test with thiobarbituric acid]. Lab. delo – Lab. Work, 11, 41-43 [in Russian].
Chevari, S., Chaba, I., & Sekey, I. (1985). Rol superoksiddismutazy v okislitelnykh protsessakh kletki i metod opredeleniya ee v biologicheskikh materialakh [The role of superoxide dismutase in the oxidative processes of the cell and the method for its determination in biological materials]. Lab. delo – Lab. Work, 11, 678-681 [in Russian].
Korolyuk, M.A., Ivanova, L.I., & Mayorova, I.G. (1988). Metod opredeleniya aktivnosti katalazy [Method for determining the activity of catalase]. Lab. delo – Lab. Work, 1, 16-19 [in Russian].
Ellman, G.L. (1959). Tissue sulfhydryl groups. Arch. Biochem. Biophys, 82, 70-77.
Eshchenko, N.D., & Volskii, G.G. (1982). Opredeleniye kolichestva yantarnoy kisloty i aktivnosti suktsinatdegidrogenazy [Determination of amber acid and succinate dehydrogenase activity]. Metody biokhimicheskikh issledovaniy – Methods of Biochemical Research. Leningrad: Izd-vo Leningradskogo universiteta [in Russian].
Krivchenkova, R.S. (1977). Opredelenie aktivnosti tsitokhromoksidazy v suspenzii mitokhondriy [Determination of the activity of cytochrome oxidase in suspension of mitochondria]. Sovremennye metody v biokhimii – Modern Methods in Biochemistry. Orekhovich, V.N. (Eds.). Moscow: Meditsina [in Russian].
Lowry, О.М., Rosebrough, N.J., Farr, A.L., & Randall, R.J. (1951). Protein measurement with the Folin phenol reagent. J. Biol. Chem., 193 (1), 265-275.
Yaremchuk, O.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].
Pope, S., Land, J.M., & Heales, S.J.R. (2008) Oxidative stress and mitochondrial dysfunction in neurodegeneration; cardiolipin a critical target? Biochim. et Biophysica Acta., 1777 (7-8), 794-799.