Effects of phenethyl isothiocyanate on acetaminophen metabolism and hepatotoxicity in mice

Toxicology and Applied Pharmacology
Y LiC S Yang

Abstract

Phenethyl isothiocyanate (PEITC), a compound derived from cruciferous and other vegetables, is a potent inhibitor of cytochrome P450 2E1. This enzyme catalyzes the bioactivation of acetaminophen (APAP) and many other xenobiotics. The present study investigated the effects of PEITC on APAP metabolism and associated hepatotoxicity in Swiss-Webster mice. When PEITC (19-150 micromol/kg) was given to mice intragastrically 1 hr before or immediately prior to a toxic dose of APAP, the APAP-induced hepatotoxicity was significantly decreased or was completely prevented. The extent of toxicity was evaluated by mortality, serum levels of glutamic-pyruvic transaminase, lactate dehydrogenase, and liver histopathology. Pretreatment of mice with ethanol enhanced APAP hepatotoxicity; this enhanced toxicity could also be prevented by the administration of PEITC. PEITC treatment prevented the depletion of hepatic glutathione levels caused by oxidized APAP metabolites. PEITC treatment also significantly decreased the plasma levels of oxidized APAP metabolites (analyzed as APAP-glutathione, APAP-cysteine, and APAP-N-acetylcysteine) and reduced the urinary excretion of APAP-cysteine. In microsomal incubations, PEITC effectively inhibited the rate o...Continue Reading

Citations

Feb 24, 2001·Drug Metabolism and Drug Interactions·T J Smith, C S Yang
Jan 4, 2001·Drug Metabolism Reviews·S S Hecht
Jul 5, 2005·Expert Opinion on Investigational Drugs·J WuM A Zern
Sep 5, 2006·Journal of Pineal Research·Tatsuya MatsuraYoshiji Ohta
Feb 11, 2014·Molecular Nutrition & Food Research·Parul GuptaSanjay K Srivastava
Aug 28, 2004·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·K H JanbazA H Gilani
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