Hepatic glutathione and hepatotoxicity: changes induced by selected narcotics.
Propoxyphene and morphine lowered hepatic glutathione and increased serum glutamic-pyruvic transaminase (SGPT) activity when administered to male mice. Maximal changes were seen at 3 to 6 hr after administration, but the effects lasted for as long as 18 hr. Morphine-induced hepatic changes potentiated both acetaminophen and cocaine-induced hepatotoxicity. Naltrexone, a narcotic antagonist, abolished the glutathione depletion produced by both propoxyphene and morphine, but did not alter the propoxyphene-induced elevations of SGPT. Naltrexone also was tested against other narcotic agonists we have previously demonstrated to be hepatotoxic. Naltrexone pretreatment of antagonized L-alpha-acetylmethadol (LAAM)-induced depletion of glutathione and elevations of SGPT. Similarly, naltrexone antagonized norLAAM-induced depletion of glutathione and elevations of SGPT, but only lessened the magnitude of the changes induced by SKF525-A. The narcotic agonists morphine, LAAM, norLAAM and propoxyphene lower hepatic glutathione and induce hepatocellular damage, but these two effects appear to be unrelated.
D000082:Acetaminophen / Q000633:toxicity; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism*; D003042:Cocaine / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009294:Narcotics / Q000494:pharmacology*; D011335:Proadifen / Q000494:pharmacology; D013997:Time Factors
D009294:Narcotics; D000082:Acetaminophen; D011335:Proadifen; D000410:Alanine Transaminase; D005978:Glutathione; D003042:Cocaine