Scavenging activity of indole compounds against cisplatin-induced reactive oxygen species

The antioxidant effects of indole compounds such as melatonin (MLT), tryptophan, and serotonin, on cisplatin (cis-diaminedichloroplatinum, or CDDP)-induced reactive oxygen species (ROS) generation were examined by electron spin resonance (ESR). In addition, DNA fragmentation by CDDP-induced ROS and the effect of MLT on it were analyzed in primary cultures of rat renal tubular epithelial cells. MLT and serotonin had scavenging effects on CDDP-induced hydroxy radicals (*OH), and the scavenging activity of MLT was higher than that of serotonin. The exposure of primary-cultured renal tubular cells to CDDP caused severe cytotoxicity. Tryptophan, serotonin, and 6-OHMLT did not reduce the CDDP-induced cytotoxicity, whereas MLT did. CDDP exposure induced DNA fragmentation in primary-cultured renal tubular cells, but the simultaneous administration of MLT inhibited the DNA fragmentation. These results indicate that MLT inhibits CDDP-induced cytotoxicity by directly scavenging *OH, and that MLT markedly reduces renal cytotoxicity and DNA fragmentation caused by CDDP-induced ROS in vitro. (c) 2006 Elsevier Inc. All rights reserved.