Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, U.S.A.
Address for correspondence: Russel J. Reiter, Department of Cellular and Structural Biology, Mail Code 7762, The University of Texas Health Science Center At San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, U.S.A. Voice: 210/567-3859; fax: 210/567-6948.
Reiter{at}uthscsa.edu
This review briefly summarizes the multiple actions by which
melatonin reduces the damaging effects of free radicals and
reactive oxygen and nitrogen species. It is well documented
that melatonin protects macromolecules from oxidative damage
in all subcellular compartments. This is consistent with the
protection by melatonin of lipids and proteins, as well as both
nuclear and mitochondrial DNA. Melatonin achieves this widespread
protection by means of its ubiquitous actions as a direct free
radical scavenger and an indirect antioxidant. Thus, melatonin
directly scavenges a variety of free radicals and reactive species
including the hydroxyl radical, hydrogen peroxide, singlet oxygen,
nitric oxide, peroxynitrite anion, and peroxynitrous acid. Furthermore,
melatonin stimulates a number of antioxidative enzymes including
superoxide dismutase, glutathione peroxidase, glutathione reductase,
and catalase. Additionally, melatonin experimentally enhances
intracellular glutathione (another important antioxidant) levels
by stimulating the rate-limiting enzyme in its synthesis,
-glutamylcysteine
synthase. Melatonin also inhibits the proxidative enzymes nitric
oxide synthase and lipoxygenase. Finally, there is evidence
that melatonin stabilizes cellular membranes, thereby probably
helping them resist oxidative damage. Most recently, melatonin
has been shown to increase the efficiency of the electron transport
chain and, as a consequence, to reduce election leakage and
the generation of free radicals. These multiple actions make
melatonin a potentially useful agent in the treatment of neurological
disorders that have oxidative damage as part of their etiological
basis.
