Peroxynitrite is a toxic oxidant formed from the reaction of superoxid
e 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-depe
ndent 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 peroxyni
trite 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 melatoni
n in various pathophysiological conditions.