Perturbation of hepatic glutathione level and glutathione-related enzyme activities by repeated administration of aminopyrine in rats.
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.
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*
D000632:Aminopyrine; D005979:Glutathione Peroxidase; D005723:gamma-Glutamyltransferase; D005978:Glutathione; D003545:Cysteine; D019803:Glutathione Disulfide