BGP-15 Protects Mitochondria in Acute, Acetaminophen Overdose Induced Liver Injury

• Published in: Pathology oncology research Vol. 26; no. 3; pp. 1797 - 1803
• Main Authors: Sarnyai, Farkas, Szekerczés, Timea, Csala, Miklós, Sümegi, Balázs, Szarka, András, Schaff, Zsuzsa, Mandl, József
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.07.2020; Springer Nature B.V
• Subjects: Acetaminophen; Acetaminophen - toxicity; Analgesics; Analgesics, Non-Narcotic - toxicity; Animals; Autophagy; Biomedical and Life Sciences; Biomedicine; Cancer Research; Chemical and Drug Induced Liver Injury - pathology; Drug overdose; Enzyme Inhibitors - pharmacology; Hepatotoxicity; Immunohistochemistry; Immunology; Liver; Liver - drug effects; Liver - pathology; Mice; Mitochondria; Mitochondria - drug effects; Oncology; Original; Original Article; Overdose; Oximes - pharmacology; Pathology; Phagocytosis; Piperidines - pharmacology; Transcription factors; Reduced glutathione; Jun-kinase; BGP-15; Acetaminophen; Mitochondrium; Liver injury
• ISSN: 1219-4956; 1532-2807
• DOI: 10.1007/s12253-019-00721-1

Acetaminophen (APAP) induced hepatotoxicity involves activation of c-Jun amino-terminal kinase (JNK), mitochondrial damage and ER stress. BGP-15, a hydroximic acid derivative, has been reported to have hepatoprotective effects in APAP overdose induced liver damage. Effect of BGP-15 was further investigated on mitochondria in APAP-overdose induced acute liver injury in mice. We found that BGP-15 efficiently preserved mitochondrial morphology, and it caused a marked decrease in the number of damaged mitochondria. Attenuation of mitochondrial damage by BGP-15 is supported by immunohistochemistry as the TOMM20 label and the co-localized autophagy markers detected in the livers of APAP-treated mice were markedly reduced upon BGP-15 administration. This effect, along with the observed prevention of JNK activation likely contribute to the mitochondrial protective action of BGP-15.