Cisplatin nephrotoxicity in cadmium-pretreated rats. Enzymatic, functional and morphological studies.
Treatment of rats with cisplatin or with cisplatin after chronic pre-exposure to cadmium induced a decrease in kidney cytochrome P-450 and glutathione levels, and in glutathione peroxidase and reductase activities. Furthermore, cadmium and cisplatin enhanced lipid peroxidation, oxidized glutathione and N-glucuronyl transferase activity. Glutathione S-transferase (substrate: 1-chloro-2,4-dinitrobenzene) was increased and decreased by cadmium and cisplatin respectively. On morphological observation, cadmium nephrotoxicity was characterized by tubular proximal damage with mitochondrial and lysosomal changes and a widespread vesiculation of tubular cells. A marked focal tubular necrosis associated with cyst formation was observed in cisplatin nephrotoxicity. On the basis of the measured biochemical, functional and histological parameters, it is concluded that cadmium pretreatment did not potentiate the nephrotoxic effect of cisplatin.
Bompart
G
G
INSERM U.133, Faculté de Médecine, Toulouse, France.
Orfila
C
C
Manuel
Y
Y
D000818:Animals; D002105:Cadmium Poisoning / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D005980:Glutathione Reductase / Q000187:drug effects; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008854:Microscopy, Electron; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D010544:Peroxidases / Q000187:drug effects; D051381:Rats; D011914:Rats, Inbred BN; D013997:Time Factors
D008315:Malondialdehyde; D003577:Cytochrome P-450 Enzyme System; D010544:Peroxidases; D005980:Glutathione Reductase; D005978:Glutathione; D002945:Cisplatin