MECHANISM OF HEPATOCYTE APOPTOSIS IN EXPERIMENTAL TOXIC LIVER INJURY



Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

One of the causes of drug hepatopathy is hepatocyte apoptosis, the mechanisms of which are still unclear. The experiments were performed in 24 Wistar rats to study the role of hepatoprotectors in the regulation of hepatocyte apoptosis in liver damage induced by administration of antituberculosis drugs (ATD). The level of apoptosis (TUNEL) was evaluated, and the expression of apoptosis-associated molecules was detected by immunohistochemistry and Western blotting. It was shown that a signaling cascade induced by ATD involved the activation of cell surface receptors (CD95) and caspase-8, i.e. apoptosis was mediated by extrinsic pathway. In addition, ATD induced p53 oncosuppressor synthesis with further activation of caspase-3 effector. Runihol administration during ATD treatment administration improved the condition of the liver, despite some apoptosis stimulating effect, mediated by an intrinsic pathway. It was found that runihol blocked both FAS- and p53-dependent pathways. Ademethionine during drug intoxication acts as a hepatoprotector, blocking extrinsic and p53-dependent pathways.

Full Text

Restricted Access

About the authors

D. L. Teplyi

Аstrakhan’State University

D. S. Sukhanov

I. I. Mechnikov North-Western Medical University

Email: dmitriysukhanovl@mail.ru

Ye. D. Bazhanova

I. M. Sechenov Institute of Evolu tionary Physiology and Biochemistry

Email: bazhanovae@mail.ru

References

  1. Аметов А. С., Кочергина И. И., Доскина Е. В. и др. Таурин в комплексной терапии метаболического синдрома и сахарного диабета. Тер. арх., 2011, т. 83, № 10, с. 31–36.
  2. Больф С. Б., Суханов Д. С. и Романцов М. Г. Медикаментозные поражения печени при полихимиотерапии туберкулёза. Вестн. Санкт-Петербургск. гос. мед. акад. им. И. И. Мечникова, 2009, № 1, с. 172–176.
  3. Борзакова С. Н., Аксенова Б. А. и Рейзис А. Р. Лекарственные поражения печени у детей, больных туберкулезом. Туберкулез и бол. лёгких, 2010, № 8, с. 3–12.
  4. Дмитриева Е. В., Москалева Е. Ю., Коган Е. А. и др. Роль системы fas/fasl в индукции апоптоза гепатоцитов при хронических вирусных гепатитах. Арх. пат., 2003, т. 65, № 6, с. 13–17.
  5. Суханов Д. С. Антиоксидантные свойства ремаксола, реамберина и адеметионина при лекарственных поражениях печени у больных на фоне противотуберкулезной терапии. Тер. арх., 2012, т. 84, № 11, с. 26–29.
  6. Удут В. В., Венгеровский А. И. и Дыгай A. M. Влияние гепатопротекторов фосфолипидной природы на процессы апоптоза при экспериментальной патологии печени, вызванной изониазидом и парацетамолом. Бюл. экспер. биол., 2012, т. 154, № 11, с. 568–571.
  7. Hazalin N. A., Ramasamy K., Lim S. M. et al. Induction of apoptosis against cancer cell lines by four ascomycetes (endophytes) from Malaysian rainforest. Phytomedicine, 2012, v. 19, № 7, p. 609–617.
  8. Miao H. L., Lei C. J., Wen J. Y. et al. Knockdown of GPC3 inhibits the proliferation of Huh7 hepatocellular carcinoma cells through down-regulation of YAP. J. Cell Biochem., 2013, v. 114, № 3, p. 625–631.
  9. Natori S., Rust C., Stadheim L. M. et al. Hepatocyte apoptosis is a pathologic feature of human alcoholiс hepatitis. J. Hepatol., 2001, v. 34, p. 248–253.
  10. Sakulnarmrat K., Fenech M., Thomas P. and Konczak I. Cytoprotective and pro-apoptotic activities of native Australian herbs polyphenolic-rich extracts. Food Chem., 2013, v. 136, № 1, p. 9–17.
  11. Santini D., Vincenzi B., Massaceisi C. et al. S-Adenosylmethionine supplementation for treatment of chemotherapy-induced liver injury. Anticancer Res., 2003, v. 23 (6D), p. 5173–5179.
  12. Sharma M., Gadang V. and Jaeschke A. Critical Role for Mixed-lineage Kinase 3 in Acetaminophen-induced Hepatotoxicity. Mol. Pharmacol., 2012, v. 82, № 5, p. 1001–1007.
  13. Tomasi M. L., Ryoo M., Skay A. et al. Polyamine and methionine adenosyltransferase 2A crosstalk in human colon and liver cancer. Exp. Cell Res., 2013, v. 319, № 12, p. 1902–1911.
  14. Zhang Y., Zhang B., Zhang A. et al. Synergistic growth inhibition by sorafenib and vitamin K2 in human hepatocellular carcinoma cells. Clinics (Sao Paulo), 2012, v. 67, № 9, p. 1093–1099.
  15. Zhao X., Cong X., Zheng L. et al. Dioscin, a natural steroid saponin, shows remarkable protective effect against acetaminophen-induced liver damage in vitro and in vivo. Toxicol Lett, 2012, v. 214, № 1, p. 69–80.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2013 Eco-Vector


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: № 0110212 от 08.02.1993.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies