Application of 1-(4-Cl-benzyl)-3-Cl- 4-(CF3-phenylamino)-1H-pyrrole-2,5-dione as a panspecific protein kinase inhibitor for inhibition of hematological complications in experimental chronic cholangitis in rats
DOI:
https://doi.org/10.15407/dopovidi2021.04.094Keywords:
pirole derivative, protein kinases inhibitor, chronic cholangitis, erythrocytes, leukocytes, plateletsAbstract
The effect of a a panspecific inhibitor of pyrrole derivatives (1-(4-Cl-benzyl)-3-Cl-4-(CF3-phenylamino)-1Hpyrrole- 2,5-dione, MI-1), synthesized at the Kyiv National Taras Shevchenko University, on hematological manifestations of experimental α-anaphthyl isothiocyanate-induced chronic cholangitis is studied. It is found that MI-1 reduces the level of inflammation, which is confirmed by the normalization of the total number of leukocytes in blood due to a decrease in the number of eosinophilic and neutrophilic granulocytes and lymphocytes involved in the development of experimental chronic cholangitis. MI-1 restores the number of erythrocytes in blood through the activation of erythropoiesis, that is evident by an increase in the number of reticulocytes in blood of rats with experimental cholangitis. MI-1 normalizes the number of platelets in blood most likely due to inhibition of platelet formation in bone marrow, activated by the development of an inflammatory process in liver. MI-1 reduces the level of hematological complications of experimental chronic cholangitis in rats and with proven low overall and hematoxicity and hepatoprotective effect is promising for further research as a compound with anti-inflammatory activity.
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Galoosian, A., Hanlon, C., Zhang, J., Holt, E. W. & Yimam, K. K. (2020). Clinical updates in primary biliary cholangitis: trends, epidemiology, diagnostics, and new therapeutic approaches. J. Clin. Transl. Hepatol., 8, No. 1, pp. 49-60. https://doi.org/10.14218/JCTH.2019.00049
Pinto, C., Giordano, D. M., Maroni, L. & Marzioni M. (2018). Role of inflammation and proinflammatory cytokines in cholangiocyte pathophysiology. Biochim. Biophys. Acta. Mol. Basis. Dis., 1864, Iss. 4, Pt. B, pp. 1270-1278. https://doi.org/10.1016/j.bbadis.2017.07.024
Gidwaney, N. G., Pawa, S. & Das K. M. (2017). Pathogenesis and clinical spectrum of primary sclerosing cholangitis. World. J. Gastroenterol., 23, No. 14, pp. 2459-2469. https://doi.org/10.3748/wjg.v23.i14.2459
Weiss, G., Ganz, T. & Goodnough, L. T. (2019). Anemia of inflammation. Blood, 133, No. 1, pp. 40-50. https:// doi.org/10.1182/blood-2018-06-856500
Kuznietsova, H. M., Dziubenko, N. V., Lynchak, O. V., Tykhoniuk, O. I., Milokhov, D. S., Khilya, O. V. & Rybalchenko, V. K. (2018). Hepatoprotective effect of protein kinase inhibitor 1-(4-Cl-benzyl)-3-chloro-4- (CF3-phenylamino)-1H-pyrrole-2,5-dione on rats’ acute cholangitis. Dopov. Nac. akad. nauk Ukr., No. 5, pp. 83-90. https://doi.org/10.15407/dopovidi2018.05.083
Fickert, P., Pollheimer, M. J., Beuers, U., Lackner, C., Hirschfield, G., Housset, C., Keitel, V., Schramm, С., Marschall, H.-U., Karlsen, T.H., Melum, E., Kaser, A., Eksteen, B., Strazzabosco, M., Manns, M. & Trauner, M. (2014). Characterization of animal models for primary sclerosing cholangitis (PSC). J. Hepatol., 60, No. 6, pp. 1290-1303. https://doi.org/10.1016/j.jhep.2014.02.006
Snook, J. A., Chapman, R. W., Sachdev, G. K., Heryet, A., Kelly, P. M., Fleming, K. A. & Jewell D. P. (1989). Peripheral blood and portal tract lymphocyte populations in primary sclerosing cholangitis. J. Hepatol., 9, No. 1, pp. 36-41. https://doi.org/10.1016/0168-8278(89)90073-1
Tsuneyama, K., Baba, H., Morimoto, Y., Tsunematsu, T. & Ogawa H. (2017). Primary biliary cholangitis: its pathological characteristics and immunopathological mechanisms. J. Med. Invest., 64, No. 1.2, pp. 7-13. https://doi.org/10.2152/jmi.64.7
Fragulidis, G. P., Vezakis, A. I., Kontis, E. A., Pantiora, E. V., Stefanidis, G. G., Politi, A. N., Koutoulidis, V. K., Mela, M. K. & Polydorou, A. A. (2016). Eosinophilic cholangitis — a challenging diagnosis of benign biliary stricture: a case report. Medicine (Baltimore), 95, No. 1, e2394. https://doi.org/10.1097/ MD.0000000000002394
Byelinska, I. V., Kuznietsova, H. M., Dziubenko, N. V., Lynchak, O. V., Rybalchenko, T. V., Prylutskyy, Yu. I., Kyzyma, O. A., Ivankov, O., Rybalchenko, V. K. & Ritter U. (2018). Effect of С60 fullerenes on the intensity of colon damage and hematological signs of ulcerative colitis in rats. Mater. Sci. Eng. C Mater. Biol. Appl., 93, pp. 505-517. https://doi.org/10.1016/j.msec.2018.08.033
Kapellos, T. S., Bonaguro, L., Gemünd, I., Reusch, N., Saglam, A., Hinkley, E. R. & Schultze J. L. (2019). Human monocyte subsets and phenotypes in major chronic inflammatory diseases. Front. Immunol., 10, 2035. https://doi.org/10.3389/fimmu.2019.02035
Byelinska, I. V., Lynchak, O. V., Rybalchenko, T. V., Yablonska, S. V., Bahurynska, O. M. & Rybalchenko, V. K. (2015). Morphofunctional parame ters of blood cells of a rat with 1,2-dimethylhydrazi ne-induced colon carcino genesis. Cytol. Genet., 49, No. 3, pp. 158-164. https://doi.org/10.3103/S0095452715030044
Scott, M. K. D., Quinn, K., Li, Q., Carroll, R., Warsinske, H., Vallania, F., Chen, S., Carns, M. A., Aren, K., Sun, J., Koloms, K., Lee, J., Baral, J.., Kropski, J., Zhao, H., Herzog, E., Martinez, F. J., Moore, B. B., Hinchcliff, M., Denny, J., Kaminski, N., Herazo-Maya, J. D., Shah, N. H. & Khatri, P. (2019). Increased monocyte count as a cellular biomarker for poor outcomes in fibrotic diseases: a retrospective, multicentre cohort study. Lancet. Respir. Med., 7, pp. 497-508. https://doi.org/10.1016/S2213-2600(18)30508-3
Byelinska, I. V., Rybalchenko, T. V., Tsyvinska, S. M. & Rybalchenko, V. K. (2017). The hematological effects of the protein kinases inhibitor maleimide derivative and 5-fluorouracil. Fiziol Zh., 63, No. 4, pp. 37-47 (in Ukrainian). https://doi.org/10.15407/fz63.04.037
Joshi, N. & Rajeshwari, K. (2009). Deflazacort. J. Postgrad. Med., 55, Iss. 4, pp. 296-300. https://doi. org/10.4103/0022-3859.58942
Lisman, T. & Luyendyk, J. P. (2018). Platelets as modulators of liver diseases. Semin. Thromb. Hemost., 44, No. 2, pp. 114-125. https://doi.org/10.1055/s-0037-1604091
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