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- Title
Acetaminophen-induced hepatotoxicity: different mechanisms of acetaminophen-induced ferroptosis and mitochondrial damage.
- Authors
Yamada, Naoya; Komada, Takanori; Ohno, Nobuhiko; Takahashi, Masafumi
- Abstract
APAP administration induces hepatotoxicity, lipid peroxidation, and glutathione (GSH) depletion, and these were markedly suppressed by the ferroptosis-specific inhibitor Ferrostatin-1 (Fer-1), the iron chelator deferoxamine, and -tocopherol (vitamin E), indicating that ferroptosis in hepatocytes contributes to the development of APAP-induced hepatotoxicity. Because APAP is metabolized by the CYP2E1 and generates I N i -acetyl I p i -benzoquinone imine (NAPQI), which binds to GSH and leads to GSH depletion (Jaeschke [9]), it is likely that mitochondria is involved in APAP-induced ferroptosis. To explore the involvement of mitochondria in APAP-induced ferroptosis and hepatotoxicity, we performed transmission electron microscopy (TEM) to analyze morphological change of mitochondria in hepatocytes of mice treated with APAP with or without Fer-1.
- Subjects
HEPATOTOXICOLOGY; OMEGA-6 fatty acids; GOLGI apparatus; MONOUNSATURATED fatty acids; HEART cells; UNSATURATED fatty acids
- Publication
Archives of Toxicology, 2020, Vol 94, Issue 6, p2255
- ISSN
0340-5761
- Publication type
Letter
- DOI
10.1007/s00204-020-02722-5