Hepatoprotective effect of protein kinase inhibitor 1-(4-Cl-benzyl)-3-chloro-4-(CF3-phenylamino)-1H-pyrrole-2,5-dione on rats' acute cholangitis

1Kuznietsova, HM, 1Dziubenko, NV, 1Lynchak, OV, 1Tykhoniuk, OI, 1Milokhov, DS, 1Khilya, OV, 1Rybalchenko, VK
1ESC "Institute of Biology and Medicine", Taras Shevchenko National University of Kyiv
Dopov. Nac. akad. nauk Ukr. 2018, 5:83-90
Section: Biology
Language: Ukrainian

The effect of protein kinase inhibitor 1-(4-Cl-benzyl)-3-chloro-4-(CF3-phenylamino)-1H-pyrrole-2,5-dione (MI-1) on liver states of rats experienced α-naphthyl isothiocyanate-induced acute cholangitis in comparison with an tiinflammatory drug prednisolone is investigated. Both prednisolone and MI-1 attenuated cholangitis manifestations and partially restored the liver functional activity: prednisolone decreased serum transaminases acti vities, while MI-1 leveled direct and total bilirubin, which could indicate its effectiveness for correcting the investigated pathology.

Keywords: 1-(4-Cl-benzyl)-3-chloro-4-CF3-phenylamino)-1H-pyrrole-2;5-dione, acute cholangitis, prednisolone
  1. Molodecky, N. A., Kareemi, H., Parab, R., Barkema, H. W., Quan, H., Myers, R. P. & Kaplan, G. G. (2011). Incidence of primary sclerosing cholangitis: a systematic review and meta-analysis. Hepatology, 53, pp. 1590-1599. doi: https://doi.org/10.1002/hep.24247
  2. Cullen, S. & Chapman, R. (2003). Primary sclerosing cholangitis. Autoimmun. Rev., 2, No. 6, pp. 305-312. doi: https://doi.org/10.1016/S1568-9972(03)00030-2
  3. Zhu, G. Q., Shi, K. Q., Huang, G. Q., Wang, L. R., Lin, Y. Q., Braddock, M., Chen, Y. P., Zhou, M. T. & Zheng, M. H. (2015). A network meta-analysis of the efficacy and side effects of UDCA-based therapies for primary sclerosing cholangitis. Oncotarget, 6, No. 29, pp. 26757-26769. doi: https://doi.org/10.18632/oncotarget.5610
  4. Batskov, S. S. (2014). Gastroenterology and hepatology. St.-Petersburg: Polytechnika-Service (in Russian).
  5. Karlsen, T., Folseraas, T., Thorburn, D. & Vesterhus, M. (2017) Primary sclerosing cholangitis — a com prehensive review. J. Hepatology, 67, pp. 1298-1323. doi: https://doi.org/10.1016/j.jhep.2017.07.022
  6. Chung, B. K., Karlsen, T. H., & Folseraas, T. (2017). Cholangiocytes in the pathogenesis of primary sclerosing cholangitis and development of cholangiocarcinoma. Biochim. Biophys. Acta, pii: S0925-4439(17)30302-2. doi: https://doi.org/10.1016/j.bbadis.2017.08.020
  7. Fickert, P., Pollheimer, M. J., Beuers, U., Lackner, C., Hirschfield, G., Housset, C., Keitel, V., Schramm, S., 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, pp. 1290-1303. doi: https://doi.org/10.1016/j.jhep.2014.02.006
  8. Dubinina, G. G., Chupryna, O. O., Platonov, M. O., Borisko, P. O., Ostrovska, G. V., Tolmachov, A. O. & Shtil, A. A. (2007). In silico design of protein kinase inhibitors: successes and failures. Anticancer Agents Med. Chem., 7, No. 2, pp. 171-188. doi: https://doi.org/10.2174/187152007780058704
  9. Dubinina, G., Golovach, S., Kozlovsky, V., Tolmachov, A. O. & Volovenko, Yu. M. (2007). Antiproliferative action of the new derivatives of l-(4-R-benzyl)-3-R1-4-(R2-phenylamino)-1H-pyrrol-2,5-dione. Zurn. organ. ta farmacevt. khimii, 5, No. 1, pp. 39-49 (in Ukrainian).
  10. Kuznietsova, H. M., Lynchak, O. V., Danylov, M. O., Kotliar, I. P. & Rybalchenko, V. K. (2013). Effect of dihydropyrrol and maleimide derivatives on the state of liver and colon in normal rats and those with colorectal carcinogenesis induced by dimethylhydrazine. Ukr. Biochem. J., 85, No. 3, pp.74-84.
  11. Kuznietsova, H. M., Yena, M. S., Kotlyar, I. P., Ogloblya, O. V. & Rybalchenko, V. K. (2016). Antiinflammatory effects of protein kinase inhibitor pyrrol derivate. Sci. World J., 2016, 2145753. doi: https://doi.org/10.1155/2016/2145753
  12. Chapman, R. W. (2017). Update on primary sclerosing cholangitis. Clin. Liver Disease, 9, No. 5, pp.107-110. doi: https://doi.org/10.1002/cld.633
  13. Hall, C., Sato, K., Wu, N., Zhou, T., Kyritsi, K., Meng, F., Glaser, S. & Alpini, G. (2017). Regulators of cho langiocyte proliferation. Gene Expr., 17, No. 2, pp. 155-171. doi: https://doi.org/ 10.3727/ 105221616X692568
  14. Lesage, G., Glaser, S., Ueno, Y., Alvaro, D., Baiocchi, L., Kanno, N., Phinizy, J. L., Francis, H. & Alpini, G. (2001). Regression of cholangiocyte proliferation after cessation of ANIT feeding is coupled with increased apoptosis. Am. J. Physiol. Gastrointest. Liver Physiol., 281, No. 1, pp. G182-G190. doi: https://doi.org/10.1152/ ajpgi.2001.281.1.G182
  15. Fabris, L., Cadamuro, M., Fiorotto, R., Roskams, T., Spirli, C., Melero, S., Sonzogni, A., Joplin, R.E., Oko licsanyi, L. & Strazzabosco, M. (2006). Effects of angiogenic factor overexpression by human and rodent cholan giocytes in polycystic liver diseases. Hepatology, 43, No. 5, pp. 1001-1012. doi: https://doi.org/10.1002/hep.21143