Effect of cisplatin, carboplatin and stobadine on lipid peroxidation of kidney homogenate and phosphatidylcholine liposomes.
The effects of the nephrotoxic, anticancer agents cisplatin (CDDP) and carboplatin (CBDCA), and the free radical scavenger, stobadine, were investigated on lipid peroxidation (LPO) of rat kidney homogenates and phosphatidylcholine (PC) liposomes. Kidney homogenates were incubated in air at 37 degrees C for 6-48 h and lipid peroxidation was detected spectroscopically as absorbance (533 nm) of the thiobarbituric acid-malondialdehyde (TBA-MDA) complex. CDDP (0.3-10 mmol.l-1) increased LPO of the homogenate. CBDCA decreased the TBA-MDA absorbance, yet was found to interfere with MDA, TBA and/or with the TBA-MDA complex. Thus when CBDCA is involved, the TBA-MDA method for detection of LPO is not suitable. Stobadine (0.1 mmol.l-1 and 1 mmol.l-1) inhibited LPO either in the control homogenate and in the homogenate where peroxidation was increased by CDDP. The effect of CDDP and CBDCA on peroxidation of PC liposomes was monitored as oxygen consumption using a Clark-type oxygen electrode. CDDP increased but CBDCA decreased the rate of oxygen consumption during the peroxidation of liposomes induced by FeSO4. The results suggest that the effects of CDDP and CBDCA on LPO may be linked with their nephrotoxicity.
Gergeĺ
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Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava.
Misík
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Ondrias
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D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002243:Carbolines / Q000494:pharmacology*; D016190:Carboplatin / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D004337:Drug Carriers; D005260:Female; D007668:Kidney / Q000378:metabolism* / Q000648:ultrastructure; D015227:Lipid Peroxidation / Q000187:drug effects*; D008081:Liposomes; D008297:Male; D010101:Oxygen Consumption; D010713:Phosphatidylcholines / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D002243:Carbolines; D004337:Drug Carriers; D008081:Liposomes; D010713:Phosphatidylcholines; D016190:Carboplatin; D002945:Cisplatin; C100106:dicarbine