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-OH-MLT 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.
Fukutomi
Junya
J
Clinical Trials Center, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, 216-8511, Japan. ctrialc@marianna-u.ac.jp
Fukuda
Atsushi
A
Fukuda
Satoshi
S
Hara
Masayuki
M
Terada
Atsushi
A
Yoshida
Minoru
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D017665:Hydroxyl Radical / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D000970:Antineoplastic Agents; D016166:Free Radical Scavengers; D007211:Indoles; D017665:Hydroxyl Radical; D002945:Cisplatin