[Mechanism of hepatocyte apoptosis in experimental toxic liver injury].
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.
D L
DL
Teplyĭ
D S
DS
Sukhanov
E D
ED
Bazhanova
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000096:biosynthesis; D053181:Caspase 8 / Q000096:biosynthesis; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes; D007538:Isoniazid / Q000008:administration & dosage; D020011:Protective Agents / Q000008:administration & dosage*; D011718:Pyrazinamide / Q000008:administration & dosage; D051381:Rats; D012436:S-Adenosylmethionine / Q000008:administration & dosage; D015398:Signal Transduction / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D019014:fas Receptor / Q000096:biosynthesis
D020011:Protective Agents; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor; D011718:Pyrazinamide; D012436:S-Adenosylmethionine; C505528:Casp8 protein, rat; D053148:Caspase 3; D053181:Caspase 8; D007538:Isoniazid