Modification of cisplatin toxicity by antioxidants.

cis-Diamminedichloroplatinum II (cisplatin) is a potent anticancer chemotherapeutic agent. The major limitation in its use is nephrotoxicity, caused by an unknown mechanism. Injection of cisplatin into rats caused a decrease in body weight and an increase in blood urea nitrogen (BUN). These effects were modified by giving a radical scavenger, alpha-tocopherol, before the cisplatin injection. N-N'-diphenyl-p-phenylenediamine, another powerful radical scavenger, also attenuated the increase in BUN induced by cisplatin. These results suggest that the toxic effects of cisplatin may be related to free radical induced damage.