HMOX1 GENE EXPRESSION IN THE LIVER OF RATS WITH EXPERIMENTAL TETRACHLOROMETHANE HEPATITIS AND ITS CHANGE UNDER THE INFLUENCE OF HEPATOPROTECTORS

Cover Page

Cite item

Full Text

Abstract

The article presents the comparative effect of hepatoprotective drugs (heptral, mexidol and methyluracil) on the expression of the HMOX1 gene in toxic liver damage induced by carbon tetrachloride (CCl4). Studies were performed on 70 male white outbred rats. Changes in the expression of the HMOX1 gene were more pronounced 72 hours after administration of CCl 4. However, under the influence of drugs, changes in expression multiplicity were most marked after 24 hours. The expression of the HMOX1 gene increased in response to all these treatments. The most pronounced response was obtained with the use of oxymethyluracil. Thus, under the toxic action of CCl4 hepatoprotective drugs enhanced protective and adaptive mechanisms, inducing the activity and expression of the HMOX1 gene.

About the authors

G. F. Mukhammadieva

Ufa Research Institute of Occupational Health and Human Ecology

Author for correspondence.
Email: ufniimt@mail.ru
450106, Ufa Russian Federation

D. O. Karimov

Ufa Research Institute of Occupational Health and Human Ecology

Email: karimovdo@gmail.com
450106, Ufa Russian Federation

A. B. Bakirov

Ufa Research Institute of Occupational Health and Human Ecology

Email: fbun@uniimtech.ru
450106, Ufa Russian Federation

T. G. Kutlina

Ufa Research Institute of Occupational Health and Human Ecology

Email: tanya.kutlina.92@mail.ru
450106, Ufa Russian Federation

Ya. V. Valova

Ufa Research Institute of Occupational Health and Human Ecology

Email: Q.juk@yandex.ru
450106, Ufa Russian Federation

E. R. Kudoyarov

Ufa Research Institute of Occupational Health and Human Ecology

Email: e.kudoyarov@yandex.ru
450106, Ufa Russian Federation

N. Yu. Khusnutdinova

Ufa Research Institute of Occupational Health and Human Ecology

Email: h-n-yu@yandex.ru
450106, Ufa Russian Federation

References

  1. Agzamova G.S., Alieva A.M. Clinical features of toxic hepatitis and its treatment (literature review). Occupational Medicine and Industrial Ecology, 2009. No. 12.- Pp. 44-47 (in Russian).
  2. Dai Y., Cederbaum A.I. Inactivation and degradation of human cytochrome P4502E1 by CCl4 in a transfected HepG2 cell line. J Pharmacol Exp Ther. 1995; 275(3): 1614-22.
  3. Shabanov P.D., Sultanov V.S., Lebedev V.A., Bychkov E.R., Proshin S.N. Effects of the polyprenol drug Roprenol in toxic liver and brain damage in rats: study of the functional state of the liver, behavior and metabolism of monoamines in the brain. Reviews of clinical pharmacology and drug therapy, 2010.- Vol. 8. – Iss. 3.- Pp. 7-30 (in Russian).
  4. Limaye P.B., Apte U.M., Shankar K., Bucci T.J., Warbritton A., Mehendale H.M. Calpain released from dying hepatocytes mediates progression of acute liver injury induced by model hepatotoxicants. Toxicol Appl Pharmacol. 2003; 191(3): 211-26.
  5. Manibusan M.K., Odin M., Eastmond D.A. Postulated carbon tetrachloride mode of action: a review. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2007; 25(3): 185-209.
  6. Sun F., Hamagawa E., Tsutsui C., Ono Y., Ogiri Y., Kojo S. Evaluation of oxidative stress during apoptosis and necrosis caused by carbon tetrachloride in rat liver. Biochim Biophys Acta. 2001; 1535(2): 186-91.
  7. Wu Y., Li L., Wen T., Li Y.Q. Protective effects of echinacoside on carbon tetrachloride-induced hepatotoxicity in rats. Toxicology. 2007; 232(1-2): 50-6.
  8. Shi J., Aisaki K , Ikawa Y , Wake K. Evidence of hepatocyte apoptosis in rat liver after the administration of carbon tetrachloride. Am J Pathol. 1998; 153(2): 515-25.
  9. Katikova O.Yu., Ruzov V.I., Smirnov L.D. Correction with Mexidol hepatotoxicity in rats caused by the introduction of tuberculostatics. Biomedical chemistry, 2004.- Vol. 50.- Iss. 6. Pp. 600-604 (in Russian).
  10. Ragulina V.A., Pokrovsky M.V., Orlova E.A., Konoplya A.I., Avdeeva E.V., Loktionov A.L. Antioxidant effects of 3-hydroxypyridine derivatives in normal and acute tetrachloromethane hepatopathy. Kuban Scientific Medical Bulletin, 2010. Vol. 7.- Pp. 124-127 (in Russian).
  11. Bakirov A.B., Myshkin V.A., Repina E.F., Karimov D.O., Gimadieva A.R., Timasheva G.V. et al. Overcoming hepatotoxicity of persistent organic pollutants: the role of antioxidants of pyrimidine structure. Occupational Health and Medical Ecology, 2016.- Vol. 52. – Iss. 3. Pp. 3-18 (in Russian).
  12. Li Volti G., Sacerdoti D., Di Giacomo C., Barcellona M.L., Scacco A., Murabito P. et al. Natural heme oxygenase-1 inducers in hepatobiliary function. World J Gastroenterol. 2008; 14(40): 6122-32.
  13. Wen T., Guan L., Zhang Y.L., Zhao J.Y. Dynamic changes of heme oxygenase-1 and carbon monoxide production in acute liver injury induced by carbon tetrachloride in rats. Toxicology. 2006; 228(1): 51-7.
  14. Schiaffonati L., Tiberio L. Gene expression in liver after toxic injury: analysis of heat shock response and oxidative stress-inducible genes. Liver. 1997; 17(4): 183-91.
  15. Nakahira K., Takahashi T., Shimizu H., Maeshima K., Uehara K., Fujii H. et al. Protective role of heme oxygenase-1 induction in carbon tetrachloride-induced hepatotoxicity. Biochem Pharmacol. 2003; 66(6): 1091-105.
  16. Petrache I., Otterbein L., Alam J., Wiegand G.W., Choi A.M. Heme oxygenase1- inhibits TNF-α-induced apoptosis in cultured fibroblasts. Am. J. Physiol. Lung. Cell Mol. Physiol.;2000 9-312:(2) 278.
  17. Farombi E.O., Surh Y.J. Heme oxygenase1- as a potential therapeutic target for hepatoprotection. J Biochem Mol Biol. 91-479:(5)39;2006.
  18. Myshkin V.A., Enikeev D.A., Srubilin D.V., Repina E.F., Gimadieva A.R., Gabdrakhmanova I.D. Protection of the liver with oxymethyluracil and succinic acid derivatives when exposed to carbon tetrachloride in the experiment. Pathological Physiology and Experimental Therapy, 2017. Vol. 61.- Iss. 3. – Pp.-97 102 (in Russian).
  19. Farashchuk N.F. Mexidol and hepatitis: experimental results and prospects in the clinic. Bulletin of Experimental Biology and Medicine, 2006.- Annex 1.- Pp. 249-242 (in Russian).
  20. Randle L.E., Goldring C.E., Benson C.A., Metcalfe P.N., Kitteringham N.R., Park B.K. et al. Investigation of the effect of a panel of model hepatotoxins on the Nrf-2 Keap1 defence response pathway in CD1-mice. Toxicology. 60-249:(3)243;2008.
  21. Abraham N., Kappas A. Pharmacological and clinical aspects of Heme Oxygenase. Pharm. reviews. ;2008 127-79:(1)60.
  22. Primiano T., Kensler T.W., Kuppusamy P., Zweier J.L., Sutter T.R. Induction of hepatic heme oxygenase1- and ferritin in rats by cancer chemopreventive dithiolethiones. Carcinogenesis. ;1996 6-2291 :(11)17.
  23. Upadhyay S., Dixit M. Role of Polyphenols and Other Phytochemicals on Molecular Signaling. Oxid Med Cell Longev. 504253:2015; 2015.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2019 Mukhammadieva G.F., Karimov D.O., Bakirov A.B., Kutlina T.G., Valova Y.V., Kudoyarov E.R., Khusnutdinova N.Y.


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 81728 от 11 декабря 2013.