Melatonin is a scavenger of peroxynitrite.
Peroxynitrite is a toxic oxidant formed from the reaction of superoxide and nitric oxide under conditions of inflammation and oxidant stress. Here we demonstrate that the pineal neurohormone melatonin inhibits peroxynitrite-mediated oxidant processes. Melatonin caused a dose-dependent inhibition of the oxidation of dihydrorhodamine 123 to rhodamine in vitro. Moreover, in cultured J774 macrophages, melatonin inhibited the development of DNA single strand breakage in response to peroxynitrite and reduced the suppression of mitochondrial respiration. Thus, melatonin appears to be a scavenger of peroxynitrite. This action may contribute to the antioxidant and antiinflammatory effects of melatonin in various pathophysiological conditions.
Gilad
E
E
Children's Hospital Medical Center, Division of Critical Care, Cincinnati, Ohio 45229, USA.
Cuzzocrea
S
S
Zingarelli
B
B
Salzman
A L
AL
Szabó
C
C
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D004249:DNA Damage / Q000187:drug effects; D004277:DNA, Single-Stranded / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009566:Nitrates / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D012235:Rhodamines / Q000378:metabolism
D000975:Antioxidants; D004277:DNA, Single-Stranded; D009566:Nitrates; D012235:Rhodamines; C058319:dihydrorhodamine 123; C039642:peroxynitric acid; D008550:Melatonin