Cisplatin nephrotoxicity in lead-pretreated rats: enzymatic and morphological studies.
Treatment of rats with cisplatin or with cisplatin after chronic pre-exposure to lead induced a decrease in cytochrome P-450, reduced glutathione (GSH), GSH-S-transferase, reductase and peroxidase activities, and an increase in N-glucuronyl transferase, lipid peroxidation and oxidized glutathione (GSSG). On histological examination, rats treated by lead or cisplatin and by lead + cisplatin revealed significant proximal tubular lesions which varied from minimal changes to severe necrosis. Lead toxicity was characterized by irregularity and thickening of glomerular basement membranes, and by tubular mitochondrial alterations associated with the presence of intranuclear inclusions. Cisplatin injury showed more extensive lesions with cellular disorganization. Except for an increase in N-glucuronyl transferase activity, lead did not exert any significant effect on these biochemical and histological parameters and did not significantly modify the deleterious effects of further therapy by cisplatin.
Bompart
G
G
INSERM U-133, Toulouse, France.
Orfila
C
C
D058186:Acute Kidney Injury / Q000139:chemically induced*; D000818:Animals; D001485:Basement Membrane / Q000187:drug effects / Q000648:ultrastructure; D002945:Cisplatin / Q000493:pharmacokinetics / Q000633:toxicity*; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D008658:Inactivation, Metabolic; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D007854:Lead / Q000493:pharmacokinetics / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D010544:Peroxidases / Q000037:antagonists & inhibitors; D051381:Rats
D065607:Cytochrome P-450 Enzyme Inhibitors; D007854:Lead; D003577:Cytochrome P-450 Enzyme System; D010544:Peroxidases; D005978:Glutathione; D002945:Cisplatin