CASPASE-3 CONTENT IN THE LIVER TISSUE IN ANTIPHOSPHOLIPID SYNDROME AND USE OF NITRIC OXIDE SYNTHESIS MODULATORS
DOI:
https://doi.org/10.11603/1811-2471.2019.v.i4.10697Keywords:
antiphospholipid syndrome, liver, nitric oxide, caspase-3Abstract
Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the presence of antibodies to negatively charged membrane phospholipids in the blood. The prevalence of APS is around 40–50 cases per 100,000 persons.
The aim of the research is to investigate the effect of L-arginine and aminoguanidine on the content of caspase-3, nitrite anions (NO2–) and nitrate anions (NO3–) in the liver tissue in APS.
Material and Methods. The study was performed on BALB/c female mice which were simulated with APS. L-arginine (25 mg/kg) and aminoguanidine (10 mg/kg) were used for correction. The content of caspase-3 in the liver tissue was assessed by Western blot analysis. The content of NO in the liver homogenates of the animals with APS was determined by the number of its stable metabolites NO2– and NO3–.
Results. An increase in the content of the active form of caspase-3 by 48 %, a decrease in the content of NO2– and an increase in the content of NO3– in the liver of the BALB/c mice with APS were established compare to control group. L-arginine caused a decrease in the content of caspase-3 by 16 %, an increase in the content of NO2– and NO3– in the liver compare to those in the group of animals with APS. Regarding introduction of aminoguanidine, the content of caspase-3 and NO2– in the liver did not change significantly, and the content of NO3– increased compare to the group of animals with APS. In the case of combined use of L-arginine and aminoguanidine, a decrease in the content of caspase-3 by 22 % was evidenced, as well as a normal content of NO2– and NO3– in the liver.
Conclusions. The use of NO L-arginine synthesis precursor alone and in combination with aminoguanidine, a selective iNOS inhibitor, leads to decreased caspase-3 content and to normalizing the levels of stable metabolites of nitric oxide NO2– and NO3– in the liver of BALB/c mice with APS.
References
Clark, K., & Giles, I. (2018). Antiphospholipid syndrome. Medicine, 46 (2), 118-125. DOI: https://doi.org/10.1016/j.mpmed.2017.11.006
Lishchuk-Iakymovych, Kh.O. (2016). Antyfosfolipidnyi syndrom u praktytsi likaria-reproduktoloha [Antiphospholipid syndrome in the practice of a reproductive physician]. Akusherstvo. Hinekolohiia. Henetyka – Obstetrics. Gynecology. Genetics, 1, 1-3 [in Ukrainian].
Ambrosino, P., Lupoli, R., Spadarella, G., Tarantino, P., Minno, A. Di., & Tarantino, L. (2015). Autoimmune liver diseases and antiphospholipid antibodies positivity: A meta-analysis of literature studies. J Gastrointestin. Liver Dis. March, 24, (1), 25-34. DOI: https://doi.org/10.15403/jgld.2014.1121.amb
Favaloro, E.J. (2013). Variability and diagnostic utility of antiphospholipid antibodies including lupus anticoagulants. Int. Jnl. Lab. Hem., 35, 269-274. DOI: https://doi.org/10.1111/ijlh.12072
Hubskyi, Yu.I., Levytskyi, Ye.L., & Horiushko, H.H. (2008). Mekhanizmy toksychnoi dii (nekroz, apoptoz) khloralkaniv na fraktsii yadernoho khromatynu klityn pechinky [Mechanisms of toxic action (necrosis, apoptosis) of chloroalkanes on nuclear chromatin fractions of liver cells]. Sovremennye problemy toksykologii – Current Problems of Toxicology, 2, 8-16 [in Ukrainian].
Kiseleva, A.V., Churlyaev, Yu.A., & Grigorev, E.V. (2019). Rol oksida azota v povrezhdenii neiyronov pri kriticheskikh sostoyaniiakh [The role of nitric oxide in damage to neurons in critical conditions]. Obshchaya reanimatologiya – General Resuscitation, 5, 80-84. doi: 10.15360/ 1813-9779-2009-5-80 [in Russian].
Aksenenko, M.B., Shestakova, L.A., & Ruksha, T.G. (2013). Ekspressiya kaspazy-3 v tkanyakh eksperimentalnoy melanomy i ee metastazov pri ingibirovanii matriksnoi metalloproteinazy [Caspase-3 expression in the tissues of experimental melanoma and its metastases during matrix metalloproteinase inhibition]. Arkhiv patologii – Pathology Archive, 1, 19-23 [in Russian].
Marushchak, M.I., Hryshchuk, L.A., & Yarema N.I. (2012). Kaspaznyi mekhanizm aktyvatsii apoptozu v patohenezi hcl-indukovanoho hostroho urazhennia lehen v eksperymenti [Caspase mechanism of apoptosis activation in the pathogenesis of hcl-induced acute lung injury in experiment]. Eksperymentalna i klinichna medytsyna – Experimental and Clinical Medicine, 2 (55), 9-13 [in Ukrainian].
Popov, S.S., Pashkov, A.N., Agarkov, A.A., & Shulgin, K.K. (2015). Intensivnost protsessov apoptoza, aktivnost akonitatgidratazy i uroven tsitrata u patsiyentov s sakharnym diabetom 2 tipa, oslozhnennym steatogepatitom, pri primenenii epifamina na fone bazisnogo lecheniya [The intensity of apoptosis processes, the activity of aconitate hydratase and the level of citrate in patients with type 2 diabetes mellitus complicated by steatohepatitis when using epifamine against the background of basic treatment]. Biomeditsinskaia khimiya – Biomedical Chemistry, 61, 3, 400-406. [in Russian]. DOI: https://doi.org/10.18097/PBMC20156103400
Guicciardi, M.E., & Gores, G.J. (2010). Apoptosis as a mechanism for liver disease progression. Semin. Liver Dis., 30 (4), 402-410. DOI: https://doi.org/10.1055/s-0030-1267540
Lei Cao, Xi-Bing Quan, Wen-Jiao Zeng, Xiao-Ou Yang and Ming-Jie Wang (2016). Mechanism of hepatocyte apoptosis. Journal of Cell Death, 9, 19- 29. DOI: https://doi.org/10.4137/JCD.S39824
Golubova, O.A. (2007). Porazhenie pecheni pri antifosfolipidnom sindrome [Liver damage in antiphospholipid syndrome]. Mystetstvo lіkuvannia: zhurnal suchasnoho lіkaria – The Art of Healing: The Journal of the Modern Doctor, 3, 35-41 [in Ukrainian].
Tsutsumi, M., Dand Takao Koike, M.D. (2000). Hepatic Manifestations of the antiphospholipid syndrome. Internal Medicine, 39, (1), 5-7. DOI: https://doi.org/10.2169/internalmedicine.39.6
Volkmann, X., Anstaett, M., & Hadem, J. (2008). Caspase activation is associated with spontaneous recovery from acute liver failure. Hepatology, 47 (5), 1624-1633. DOI: https://doi.org/10.1002/hep.22237
Tokin, I. I., Tokin, I.B., Sologub, T.V., Filimonova, G.F., Khussar, P. (2014). Immunogistokhimicheskiy analiz aktivnosti kaspazy-3 v biopsiyakh pecheni patsiyentov pri mono- i smeshannykh infektsiyakh [Immunohistochemical analysis of caspase-3 activity in liver biopsies of patients with mono- and mixed infections]. Klinitsist – The Clinician, 2, 29-32 [in Russian].
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].
Khomenko, A.V. (2013). Hidroksyliuvannia kholekaltsyferolu v hepatotsytakh shchuriv za dii prednizolonu [Hydroxylation of cholecalciferol in rat hepatocytes by the action of prednisolone]. Ukrainskyi biokhimichnyi zhurnal – Ukrainian Biochemical Journal, 85, 3, 73-78 [in Ukrainian].
Bradford, M.M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem, 72, 248-254. DOI: https://doi.org/10.1016/0003-2697(76)90527-3
Laemmli, U.K. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, 227, 5259, 680-685. DOI: https://doi.org/10.1038/227680a0
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 DOI: https://doi.org/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].
Rauch, J., Subang, R., D’Agnillo, P., Koh, J. S., Levine, J. S. J. (2000). Apoptosis and the antiphospholipid syndrome. Autoimmun., 15 (2), 231-235. DOI: https://doi.org/10.1006/jaut.2000.0396
Andreoli, L., Fredi, M., Nalli, C., Franceschini, F., Meroni P. L., & Tincani, A. (2013). Antiphospholipid antibodies mediate autoimmunity against dying cells. Autoimmunity, 46 (5), 302-306. DOI: https://doi.org/10.3109/08916934.2013.783025
Fan, T.J., Han, L.H., Cong, R.S., & Liang, J. (2005) Caspase family proteases and apoptosis. Acta Biochim Biophys Sin (Shanghai), 37 (11), 719-727. DOI: https://doi.org/10.1111/j.1745-7270.2005.00108.x
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. DOI: https://doi.org/10.1172/JCI39828
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. DOI: https://doi.org/10.3899/jrheum.100494C1
Saran, U., Mani, K.P., Balaguru, U.M., Swaminathan, A., Nagarajan, S., Dharmarajan, A.M., & Chatterjee, S. (2017). sFRP4 signalling of apoptosis and angiostasis uses nitric oxide-cGMP-permeability axis of endothelium. Nitric Oxide, 66, 30-42. doi: 10.1016/j.niox.2017.02.012. Epub 2017 Mar 4. DOI: https://doi.org/10.1016/j.niox.2017.02.012
Zhang, N., Diao, Y., Hua, R., Wang, J., Han, S., Li, J., & Yin, Y. (2017). Nitric oxide-mediated pathways and its role in the degenerative diseases. Front Biosci (Landmark Ed), 22, 824-834. DOI: https://doi.org/10.2741/4519
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].
Lopez-Pedrera, Ch., 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. DOI: https://doi.org/10.1093/rheumatology/kew054
Wiest, R., & Groszmann, R.J. (2002). The paradox of nitric oxide in cirrhosis and portal hypertension: too much, not enough. Hepatology, 35 (2), 478-491. DOI: https://doi.org/10.1053/jhep.2002.31432
Svenungsson, E., Andersson, M., Brundin, L., Vollenhoven, R., Khademi, M., Tarkowski, A., Greitz, D., Dahlström, M., Lundberg, I., & Klareskog, L. (2001). Increased levels of proinflammatory cytokines and nitric oxide metabolites in neuropsychiatric lupus erythematosus. Ann. Rheum. Dis, 60, 372-379. DOI: https://doi.org/10.1136/ard.60.4.372
Oleshchuk, O.M. (2014). Stan systemy oksydu azotu pry eksperymentalnomu tsyrozi pechinky [The state of the system of nitric oxide in experimental cirrhosis of the liver]. Visnyk problem biolohii i medytsyny – Bulletin of Problems of Biology and Medicine, 3, 2 (111), 198-202 [in Ukrainian].
Stepanov, Iu.M.,. Kononov, I.N., Zhurbina, A.I., & Filippova, A.Iu. (2004). Arginin v meditsinskoy praktike [Arginine in medical practice]. Zhurnal AMN Ukrainy – Journal of the Academy of Medical Sciences of Ukraine, 10, (1), 340–352 [in Ukrainian].
