Microcystin-induced 8-hydroxydeoxyguanosine in DNA and its reduction by melatonin, vitamin C, and vitamin E in mice.
Microcystin LR (MC-LR), a liver-specific toxin synthesized by Microcystis aeruginosa, was investigated. MC-LR initiated reactive oxygen species formation followed by damaging DNA and some other cellular components. We investigated the ability of MC-LR to induce oxidative DNA damage by examining the formation of 8-hydroxydeoxyguanosine (8-OH-dG) using HPLC with electrochemical detection. Melatonin, vitamin C (ascorbate), and vitamin E (as Trolox), all of which are free radical scavengers, markedly inhibited the formation of 8-OH-dG in a concentration-dependent manner. The concentration that reduced DNA damage by 50% (IC(50)) was 0.55, 31.4, and 36.8 microM for melatonin, ascorbate, and Trolox, respectively. The results show that melatonin is 60- and 70-fold more effective than vitamin C or vitamin E, respectively, in reducing oxidative DNA damage. These findings are consistent with the conclusion that melatonin's highly protective effect against microcystin toxicity relates, at least in part, to its direct hydroxyl radical scavenging ability.
Al-Jassabi
S
S
Department of Biological Sciences, Yarmouk University, Irbid, Jordan. sjassabis@hotmail.com
Khalil
A M
AM
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D052998:Microcystins / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D010084:Oxidation-Reduction / Q000187:drug effects; D014810:Vitamin E / Q000494:pharmacology*; D014815:Vitamins / Q000494:pharmacology
D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D052998:Microcystins; D014815:Vitamins; D014810:Vitamin E; C078588:microcystin; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D008550:Melatonin; D001205:Ascorbic Acid