Adverse effects of anti-tumor drug, cisplatin, on rat kidney mitochondria: disturbances in glutathione peroxidase activity.
This study was designed to clarify mechanisms responsible for cisplatin-induced nephrotoxicity together with the effect of selenium. Rats were divided into 3 groups: the cisplatin group; cisplatin (60 mg/kg) was administered intraperitoneally once, the cisplatin + Se group; cisplatin (60 mg/kg) once, and selenious acid (10 mumol/kg) were administered intraperitoneally once a day for 5 consecutive days, the control group; untreated. In each group, mitochondrial respiratory function, enzymic activities in mitochondrial respiratory chain and glutathione peroxidase, and plasma creatinine and BUN contents were measured. In the cisplatin group, decreases in mitochondrial respiratory function, enzymic activities in the respiratory chain and glutathione peroxidase, and increases in plasma creatinine and BUN contents were observed compared with the control group, while the cisplatin + Se group lessened these impairments. These results suggested that cisplatin-induced nephrotoxicity was closely related to mitochondrial dysfunction through the impairment of glutathione peroxidase. This toxicity might be ascribed to free radical mediated-injury. We propose here that, with selenium, higher dose administration of cisplatin to patients might be applicable.
Sugiyama
S
S
Department of Biomedical Chemistry, Faculty of Medicine, University of Nagoya, Japan.
Hayakawa
M
M
Kato
T
T
Hanaki
Y
Y
Shimizu
K
K
Ozawa
T
T
D000818:Animals; D002945:Cisplatin / Q000633:toxicity*; D004579:Electron Transport; D005979:Glutathione Peroxidase / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007700:Kinetics; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012643:Selenium / Q000494:pharmacology
D005979:Glutathione Peroxidase; D012643:Selenium; D002945:Cisplatin