ROLE OF HEPATOPROTECTORS AND IMMUNOMODULATORS IN REGULATION OF HEPATOCYTE APOPTOSIS INDUCED BY ANTITUBERCULOSIS TREATMENT

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Abstract


It was currently shown that hepatopathy due to drug toxicity is associated with increased apoptosis of hepatocytes. Therefore, development of drugs which regulate cell death is of great importance. Aim: to involve some hepatoprotectors (ademethionine, reamberin, remaxol) and immunomodulators (cycloferon) into regulation of apoptosis in experimental models of liver first-line antituberculousis drugs (isoniazid, rifampicin, pyrazinamide). Materials and methods: levels of apoptosis (TUNEL), expression of CD95 (receptor of tumor necrosis factor ― by immunohistochemistry), expression of caspase-8, caspase-3 and p53 (Western-blotting) were measured. Results: exposition of first-line antituberculousis drugs leads to dysthrophia of liver parenchyma cells with increased apoptosis of hepatocytes and activation of CD95, caspase-8 (external way) and overexpression of p53 and caspase-3. It was found that reamberin, cycloferon and remaxol have hepatoprotective effect improving liver histology; ademethionine administered by intraperitoneal injection showed no positive effects. Reamberin demonstrated apoptosis-inhibiting effect in the experiment whereas other drugs were found to be apoptosis inductors for hepatocytes in toxic hepatopathy. Conclusions: regulation of apoptosis by cycloferon and remaxol mediated by external and p53-dependent pathway is confirmed by increased expression of CD95 and p53 protein. Ademethionine might induce apoptosis by the intrinsic pathway.

 


D. S. Sukhanov

Sechenov Institute of Evolutionary Physiology and Biochemistry, St. Petersburg, Russian Federation

Author for correspondence.
Email: dmitriysukhanovl@mail.ru

Russian Federation MD, associate professor of the Department of Phthisiopulmonology and Thoracic Surgery, I.I. Mechnikov North-Western State Medical University. Address: St. Petersburg, Kirochnaya Street, 41; tel.: (812) 303-50-00

E. D. Bazhanova

Mechnikov Northwest Medical University, St. Petersburg, Russian Federation

Email: bazhanovae@mail.ru

Russian Federation PhD, leading research scientist of the Laboratory of Comparative Somnology and Neuroendocrinology, I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS. Address: 194223, St. Petersburg, Thorez avenue, 44; tel.: (812) 552-32-27

D. L. Teplyi

Аstrakhan State University, Russian Federation

Email: dima.tepliy@yandex.ru

Russian Federation PhD, professor, member of RANS, Head of the Department of Animal and Human Morphology and Physiology of Astrakhan State University. Address: 414040, Astrakhan, Tatishchev Street, 20a; tel.: (8512) 22-93-47

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