L-alpha-acetylmethadol-induced tissue alterations in mice.
Single oral dosages of the synthetic narcotic analgesic, L-alpha-acetylmethadol (LAAM) increased serum glutamic-pyruvic transaminase (SGPT) levels throughout a two-day observation period and produced a persistent depletion of hepatic and renal glutathione (GSH) levels. These LAAM-induced changes demonstrated dose- and time-dependence within that dosage range producing mortality. Histological evaluation of livers from LAAM-treated mice revealed cytoplasmic and nuclear changes in centrilobular hepatocytes. Interestingly, neither the LAAM-induced histopathological changes nor the depression of hepatic GSH were altered by the induction of hepatic metabolism following pretreatment with either phenobarbital or 3-methylcholanthrene; however, the induction of hepatic drug metabolism did abate the four-day mortality and SGPT elevations.
D000410:Alanine Transaminase / Q000097:blood*; D000818:Animals; D001806:Blood Urea Nitrogen; D005978:Glutathione / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008691:Methadone / Q000031:analogs & derivatives*; D008692:Methadyl Acetate / Q000031:analogs & derivatives* / Q000633:toxicity*; D008748:Methylcholanthrene / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009336:Necrosis; D010634:Phenobarbital / Q000494:pharmacology; D013997:Time Factors
C020783:paracymethadol; D008748:Methylcholanthrene; D000410:Alanine Transaminase; D005978:Glutathione; D008692:Methadyl Acetate; D008691:Methadone; D010634:Phenobarbital