Methotrexate-induced apoptosis in hepatocytes after partial hepatectomy

European Journal of Pharmacology
Kaoru KobayashiIkuyo Tsukamoto

Abstract

To investigate apoptosis induced by methotrexate in hepatocytes in vivo, rats received a single injection of methotrexate immediately after partial hepatectomy and apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) and gel electrophoresis of DNA. Characteristic DNA fragmentation was obvious at 2 h and peaked at 4 h after partial hepatectomy with methotrexate injection. TUNEL-positive staining was observed in nuclei and nuclear fragments of hepatocytes in the methotrexate-injected liver (partial hepatectomy with methotrexate), with negligible background staining in the control (partial hepatectomy only) and in the methotrexate-injected normal (normal with methotrexate) rat liver. The involvement of the c-Jun N-terminal kinase (JNK) activator protein 1 (AP-1) pathway and p53 in apoptosis was also examined. The activity of JNK increased at 15 min and peaked at 1 h after partial hepatectomy. This increase was repressed by methotrexate injection. Western blot analysis showed that the levels of c-Fos and c-Jun protein expression, which increased at 1 h after partial hepatectomy, were also reduced by methotrexate. The levels of p53 protein were markedly increased after partial hepate...Continue Reading

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Citations

Nov 10, 2013·The Journal of Veterinary Medical Science·Jing SunSatoshi Furukawa
May 26, 2011·Canadian Journal of Physiology and Pharmacology·Nancy ChenGideon Koren
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Dec 12, 2020·Journal of Biomolecular Structure & Dynamics·Amira AkachaLazhar Zourgui
Oct 12, 2021·Drug and Chemical Toxicology·Meltem ÖzgöçmenAli Mustafaoğlu

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