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Carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone-induced toxicities in rats: comparative study with other mitochondrial uncouplers (2,4-dinitrophenol, OPC-163493 and tolcapone).


ABSTRACT: FCCP (carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone) is known to inhibit oxidative phosphorylation as a protonophore, dissipating the proton gradient across the inner mitochondrial membrane. To understand the toxicity of FCCP, 3-day, 2- and 4-week repeated oral dose studies were performed in male rats. In the 3-day and 2-week repeated dose toxicity studies, observations included salivation, increased body temperature, and dead and moribund animals. Increased liver weight was observed in conjunction with hydropic degeneration and centrilobular necrosis of hepatocytes. In addition, pathological changes were observed in the pancreas, testis, epididymal duct, stomach and parotid gland. Electron microscopic examination revealed mitochondrial pleomorphism in the hepatocytes. Swelling of m

SUBMITTER: Inoue Y 

PROVIDER: S-EPMC10541353 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature