title: Perturbation of hepatic glutathione level and glutathione-related enzyme activities by repeated administration of aminopyrine in rats.
abstract: The influence of repeated administration of aminopyrine on the tissue glutathione level and related enzyme activities was investigated in rats. Reduced glutathione level in the liver was not changed after 5 days of treatment but a significant increase was seen after 15 days of aminopyrine treatment. Oxidized glutathione level was unaltered throughout the experiment. Repeated administration of aminopyrine for 5 days caused a marked increase in gamma-glutamyl transpeptidase activities in liver whole homogenates as well as in the nuclear fraction, but not in liver microsomes. These results suggest that gamma-glutamyl transpeptidase located in plasma membrane may be induced by repeated administration of aminopyrine for 5 days. The activities of cytosolic glutathione peroxidase, which modulates glutathione level, were also significantly increased by aminopyrine treatment. Under the same conditions, glutathione peroxidase activity with H2O2 as a substrate was unaltered, while a time-dependent increase in the activity was found when cumene hydroperoxide was used as a substrate, even after a single administration of aminopyrine. The intracellular cysteine level was increased accompanying the increased gamma-glutamyl transpeptidase activities. Therefore, induced gamma-glutamyl transpeptidase may play a role in the reclamation of extracellular oxidized glutathione.
mesh_terms: D000284:Administration, Oral; D000632:Aminopyrine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D003545:Cysteine / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism*; D019803:Glutathione Disulfide; D005979:Glutathione Peroxidase / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013347:Subcellular Fractions / Q000201:enzymology; D013997:Time Factors; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
chemical_list: D000632:Aminopyrine; D005979:Glutathione Peroxidase; D005723:gamma-Glutamyltransferase; D005978:Glutathione; D003545:Cysteine; D019803:Glutathione Disulfide