Pathways of apoptosis regulation in hepatocytes induced by first-line antitubercular drugs.

ABSTRACT

We studied pathways of apoptosis regulation during experimental hepatopathy caused by treatment with antitubercular drugs and involvement of some hepatoprotectors and immunomodulators in the regulation of hepatocyte apoptosis induced by antitubercular drugs. The intensity of apoptosis and expression of apoptosis-associated molecules were evaluated. It was shown that antitubercular drugs induce apoptosis in hepatocytes by triggering external signaling pathway and p53-dependent signaling pathway and simultaneously reducing the level of anti-apoptotic Bcl-2 protein. Runihol, remaxol, and cycloferon reduced degenerative effects in the liver, though the level of apoptosis remained high. Ademetionine in tablets and reamberin improved the microstructure of the liver by inhibiting both apoptotic pathways induced by the antitubercular drugs; in other words, they have distinct hepatoprotective and apoptosis-protective effects, which is especially important at the late stages of ontogeny.