Melatonin prevents the increase in hydroxyl radical-spin trap adduct formation caused by the addition of cisplatin in vitro

We studied the generation of reactive oxygen species (ROS) caused by cisplatin administration and the preventive effect of melatonin, the main secretory product of the pineal gland, on the reaction in vitro using electron spin resonance spectroscopy. Cisplatin induced generation of the hydroxyl radical (OH*) in phosphate buffer in pH 7.4 as a dose-dependent manner. However, OH* was not generated in phosphate buffer containing chloride ions at concentration exceeding 120 mM. The induction of OH. production by cisplatin was completely inhibited by the addition of melatonin, but not by the addition of 6-hydroxymelatonin, which is a hepatic metabolite of melatonin. Furthermore, melatonin was the most effective agent for preventing of OH* formation among various well-known antioxidants including mannitol and reduced glutathione. These results indicate that melatonin may scavenge OH. directly and thereby prevent renal tissue damage caused by OH* produced in response to cisplatin treatment.