[Role of hepatoprotectors and immunomodulators in regulation of hepatocyte apoptosis induced by antituberculosis treatment].

UNLABELLED: 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, pyraztinamide).

MATERIALS AND

METHODS

Levels of apoptoasis (TUNEL), expression of CD95 (receptor of tumor necrosis factor - by immunohistochemistry), expression of caspase-8, caspase-3 and pS3 (Western-blotting) were measured.

RESULTS

Exposition offirst-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

Legulation 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.