Pharmacological actions of melatonin in acute and chronic inflammation.
A vast number of experimental and clinical studies implicates oxygen-derived free radicals (especially, superoxide and the hydroxyl radical) and high energy oxidants (such as peroxynitrite) as mediators of acute and chronic inflammation. The purpose of this review is to summarize the pharmacological actions of melatonin in acute and chronic inflammation. Reactive oxygen species can modulate a wide range of toxic oxidative reactions. These include initiation of lipid peroxidation, direct inhibition of mitochondrial respiratory chain enzymes, inactivation of glyceraldehyde-3-phosphate dehydrogenase, inhibition of membrane sodium/potassium ATPase activity, inactivation of membrane sodium channels, and other oxidative modifications of proteins. Reactive oxygen species (e.g., superoxide, peroxynitrite, hydrogen peroxide and hydroxyl radical) are all potential reactants capable of initiating DNA single strand breakage, with subsequent activation of the nuclear enzyme poly (ADP ribose) synthetase (PARS), leading to eventual severe energy depletion of the cells, and necrotic-type cell death. These toxic reactions are likely to play a role in the pathophysiology of inflammation. Melatonin has been shown to possess both in vitro and in vivo important antioxidant activities as well as to inhibit the activation of poly (ADP ribose) synthetase. A large number of experimental studies have documented that melatonin exerts important anti-inflammatory actions.
Cuzzocrea
Salvatore
S
Institute of Pharmacology, School of Medicine, University of Messina, Gazzi, Italy. salvator@www.unime.it
Reiter
Russel J
RJ
D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism*; D008550:Melatonin / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
D016877:Oxidants; D017382:Reactive Oxygen Species; D008550:Melatonin