Prevention of acetaminophen hepatotoxicity by propylthiouracil in the glutathione depleted rat.
This study was designed to investigate the protective effect of PTU pretreatment against acetaminophen hepatotoxicity in rats whose hepatic GSH had been depleted by prior diethylmaleate (DEM) administration. A single injection of DEM depleted hepatic GSH showing lowest level after 90 min in both control and PTU pretreated rats. Triple injection schedule kept the hepatic GSH concentrations consistently very low up to 6 hr. Whereas a toxic dose of acetaminophen administration did not effect SGOT and SGPT levels after 30 hr in PTU pretreated rats given either a single or multiple injections of DEM, the same dose of acetaminophen in the control rats raised these transaminases to a very high level. High activity of transaminases was associated with significant histological hepatic damage. Our results suggest that PTU pretreatment affords significant protection against acetaminophen hepatotoxicity even under conditions when hepatic GSH concentrations have been significantly depleted prior to acetaminophen administration.
D000082:Acetaminophen / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D005609:Free Radicals; D005978:Glutathione / Q000172:deficiency; D007037:Hypothyroidism / Q000503:physiopathology; D008099:Liver / Q000187:drug effects*; D008297:Male; D008298:Maleates / Q000494:pharmacology; D011441:Propylthiouracil / Q000494:pharmacology*; D051381:Rats
D005609:Free Radicals; D008298:Maleates; D000082:Acetaminophen; D011441:Propylthiouracil; C014476:diethyl maleate; D005978:Glutathione