RT Journal Article
SR Electronic
T1 Hepatic glutathione and hepatotoxicity: changes induced by selected narcotics.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 708
OP 714
VO 221
IS 3
A1 R C James
A1 D R Goodman
A1 R D Harbison
YR 1982
UL http://jpet.aspetjournals.org/content/221/3/708.abstract
AB 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.