Increased reduced glutathione and glutathione S-transferase activity in chronic cephaloridine nephrotoxicity studies in the rat.
The effect of repeated cephaloridine treatment on renal glutathione and related enzymes has been investigated in young adult male and female Sprague-Dawley rats. Animals were given intraperitoneally daily doses of either 750 mg/kg for two weeks or 500 or 750 mg/kg for three months. Measurement of blood and urinary parameters (electrolytes, urea, creatinine) did not reveal any renal function impairment and histological examination confirmed the absence of renal damage. By contrast, an increase in reduced glutathione (2 to 3-fold) and glutathione S-transferase activity (1.5 to 2-fold) was observed. These results are consistent with the development of an adaptative phenomenon to cephaloridine subchronic treatment in the rat, leading to a tolerance to high repeated doses.
Olivier
M F
MF
Laboratoire de Toxicologie, Faculté de Pharmacie, Paris.
Dutertre-Catella
H
H
Thevenin
M
M
Martin
C
C
Warnet
J M
JM
Claude
J R
JR
D000118:Acetylglucosaminidase / Q000378:metabolism; D000626:Aminopeptidases / Q000378:metabolism; D000818:Animals; D018826:CD13 Antigens; D002509:Cephaloridine / Q000008:administration & dosage / Q000633:toxicity*; D003404:Creatinine / Q000097:blood / Q000652:urine; D004334:Drug Administration Schedule; D004573:Electrolytes / Q000097:blood / Q000652:urine; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D008871:Microvilli / Q000201:enzymology; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014508:Urea / Q000097:blood / Q000652:urine; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D004573:Electrolytes; D014508:Urea; D003404:Creatinine; D005723:gamma-Glutamyltransferase; D005982:Glutathione Transferase; D000118:Acetylglucosaminidase; D000626:Aminopeptidases; D018826:CD13 Antigens; D005978:Glutathione; D002509:Cephaloridine