Antioxidant And Pro-oxidant Activities Of Melatonin In The Presence Of Copper And Polyphenols

Melatonin,a pineal hormone,regulates biorhythms and is used as a supplement for sleep aid.The present study investigated the influence of melatonin on reactive oxygen species(ROS)generated from polyphenol autoxidation in the presence of copper.We showed that melatonin enhanced ROS formation in a redox system containing low concentrations of copper and quercetin(Que)or(-)-epigallocatechin-3-gallate(EGCG),due to reduction of cupric to cuprous ion by melatonin.Addition of DNA to this system inhibited ROS production,because DNA bound to copper and inhibited copper reduction by melatonin.When melatonin was added to a system containing high concentrations of copper and Que or EGCG,it diminished hydroxyl radical formation.Upon addition of DNA to high concentrations of copper and Que,this pro-oxidative system generated ROS and caused DNA damage,which was not prevented by typical scavenger of hydroxyl radical DMSO or mannitol.Under these conditions,melatonin or bathocuproine disulfonate(a copper chelator)protected the DNA from damage by chelating copper.Finally,the influence of melatonin on hepatotoxicity of copper and polyphenols was further studied by using in vivo models of diethyldithiocarbamate(DEDTC,a copper ionophore)and EGCG,and it was found that melatonin could significantly inhibit hepatotoxicity and DNA damage evoked by EGCG plus DEDTC.Overall,the present study demonstrates the pro-oxidant and antioxidant activities of melatonin in the redox system of copper and polyphenols,and the pro-oxidant effect is inhibited by the presence of DNA,which prevents copper reduction by melatonin.Interestingly,in vivo melatonin protects against copper/polyphenol-induced DNA damage via acting as an antioxidant rather than a pro-oxidant,and melatonin probably via acting as a copper-chelating agent rather than a hydroxyl radical scavenger.