Reducing oxidative/nitrosative stress: a newly-discovered genre for melatonin

References

• Abdel-Wahab MH, Akoul EMS and Abdel-Aziz AH. 2000. Modulatory effects of melatonin and vitamin E in doxorubicin-induced cardiotoxicity in Ehrlich ascites carcinoma-bearing mice. Tumori 86:157–162.
   Google Scholar
• Abe M, Reiter RJ, Orhii P, Hara M and Poeggeler B. 1994. Inhibitory effects of melatonin on cataract formation in newborn rats: evidence for an antioxidative role for melatonin. J Pineal Res 17:94–100.
   PubMed Web of Science ®Google Scholar
• Abe M, Itoh MT, Miyata M, Ishikawa S and Sumi Y. 1999. Detection of melatonin, its precursors and related enzyme activities in rabbit lens. Exp Eye Res 68:255–262.
   PubMed Web of Science ®Google Scholar
• Abecia JA, Forcada F and Zuniga O. 2002. The effect of melatonin on the secretion of progesterone in sheep and on the development of ovine embryos in vitro. Vet Res Commun 26:151–158.
   PubMed Web of Science ®Google Scholar
• Acuna-Castroviejo D, Reiter RJ, Menendez-Pelaez A, Pablos MI and Burgos A. 1994. Characterization of high affinity melatonin binding sites in purified cell nuclei of rat liver. J Pineal Res 16: 100–112.
   PubMed Web of Science ®Google Scholar
• Albarran MT, Lopez-Burrillo S, Pablos MI, Reiter RJ and Agapito MT. 2001. Endogenous rhythms of melatonin, total antioxidant status and superoxide dismutase activity in several tissues of chick and their inhibition by light. J Pineal Res 30:227–233.
   PubMed Web of Science ®Google Scholar
• Allegra M, Reiter RJ, Tan DX, Gentile C, Tesoriere L and Livrea MA. 2003. The chemistry of melatonin interaction with reactive species. J Pineal Res 34:1–10.
   PubMed Web of Science ®Google Scholar
• Antolin I, Obst B, Burkhardt S and Hardeland R. 1997. Antioxidative protection in a high-melatonin organism: the dinoflagellate Gonyaulax polyedra is rescued from lethal oxidative stress by strongly elevated, but physiologically possible concentrations of melatonin. J Pineal Res 23:182–190.
   PubMed Web of Science ®Google Scholar
• Antunes F, Barclay LR, Ingold KU, King M, Norris JQ, Scaiano JC and Xi F 1999. On the antioxidant activity of melatonin. Free Radic Biol Med 26:117–128.
   PubMed Web of Science ®Google Scholar
• Arendt J. 1997. Safety of melatonin in long-term use (?). J Biol Rhythms 12:673–681.
   PubMed Web of Science ®Google Scholar
• Arendt J. 2005. Melatonin as a chronobiotic. Sleep Med Rev 9:25–39.
   PubMed Web of Science ®Google Scholar
• Axelrod J, Wurtman RJ and Winget CM. 1964. Melatonin synthesis in the hen pineal gland and its control by light. Nature 201:1134.
   PubMedGoogle Scholar
• Axelrod J, Wurtman RJ and Snyder SH. 1965. Control of hydroxyindole-O-methyltransferase activity in the rat pineal gland by environmental lightening. J Biol Chem 240:949–954.
   PubMed Web of Science ®Google Scholar
• Bandyopadhyay D, Biswas K, Bandyopadhyay U, Reiter RJ and Banerjee RK. 2000. Melatonin protects against stress-induced gastric lesions by scavenging hydroxyl radicals. J Pineal Res 29:143–151.
   PubMed Web of Science ®Google Scholar
• Barlow-Walden LR, Reiter RJ, Abe M, Pablos MI, Menedez-Pelaez A, Chen LD and Poeggeler B. 1995. Melatonin stimulates brain glutathione peroxidase activity. Neurochem Int 26:497–502.
   PubMed Web of Science ®Google Scholar
• Barrett P, Conway S and Morgan PJ. 2003. Digging deep – structure-function relationships in the melatonin receptor family. J Pineal Res 35:3221–3230.
   Google Scholar
• Baydas G, Canatan H and Turkoglu A. 2002a. Comparative analysis of the protective effects of melatonin and vitamin E on streptozotocin-induced diabetes mellitus. J Pineal Res 32:225–230.
   PubMed Web of Science ®Google Scholar
• Baydas G, Gursu MF, Yilmaz S, Canpolat S, Yasar A, Cikim G and Canatan H. 2002b. Daily rhythm of glutathione peroxidase activity, lipid peroxidation and glutathione levels in tissues of pinealectomized rats. Neurosci Lett 323:195–198.
   PubMed Web of Science ®Google Scholar
• Beckman JS and Koppenol WH. 1996. Nitric oxide, superoxide, and peroxynitrite: The good, the bad and the ugly. Am J Physiol 271:C1424–C1437.
   PubMed Web of Science ®Google Scholar
• Benitez-King G. 2006. Melatonin as a cytoskeletal modulator: implications for cell physiology and disease. J Pineal Res 40:1–9.
   PubMed Web of Science ®Google Scholar
• Bertrand S, Faivre B and Sorci G. 2006. Do carotenoid-based sexual traits signal the availability of non-pigmentary antioxidants? J Exp Biol 209:4414–4419.
   PubMedGoogle Scholar
• Bjorneboe A, Bjorneboe GA and Drevon CA. 1990. Absorption, transport and distribution of vitamin E. J Nutr 120:233–242.
   PubMed Web of Science ®Google Scholar
• Blanchard B, Pompon D and Ducrocq C. 2000. Nitrosation of melatonin by nitric oxide and peroxynitrite. J Pineal Res 29:184–192.
   PubMed Web of Science ®Google Scholar
• Blask DE, Dauchy RT and Sauer LA. 2005. Putting cancer to sleep at night: the neuroendocrine/circadian melatonin signal. Endocrine 27:179–188.
   PubMed Web of Science ®Google Scholar
• Blickenstaff RT, Brandstadter SM, Reddy S and Witt R. 1994. Potential radioprotective agents. 1. Homologs of melatonin. J Pharm Sci 83:216–218.
   PubMed Web of Science ®Google Scholar
• Brizel DM. 2007. Pharmacologic approaches to radiation protection. J Clin Oncol 25:4084–4089.
   PubMed Web of Science ®Google Scholar
• Brömme HJ, Mörke W, Peschke E, Ebelt H and Peschke D. 2000. Scavenging effect of melatonin on hydroxyl radicals generated by alloxan. J Pineal Res 29:201–208.
   PubMed Web of Science ®Google Scholar
• Bubenik GA. 2002. Gastrointestinal melatonin: localization, function and clinical relevance. Dig Dis Sci 47:2336–2348.
   PubMed Web of Science ®Google Scholar
• Bubenik GA, Hacker RR, Brown GM and Bartos L. 1999. Melatonin concentrations in the luminal fluid, mucosa, and muscularis of the bovine and porcine gastrointestinal tract. J Pineal Res 26:56–63.
   PubMed Web of Science ®Google Scholar
• Cadenas S and Barja G. 1999. Resveratrol, melatonin, vitamin E, and PBN protect against renal oxidative damage induced by the kidney carcinogen KBrO3. Free Radic Biol Med 26:1531–1537.
   PubMed Web of Science ®Google Scholar
• Cahill GM and Besharse JC. 1992. Light sensitive melatonin synthesis by Xenopus photoreceptors after destruction of the inner retina. Vis Neurosci 8:487–490.
   PubMed Web of Science ®Google Scholar
• Cardinali DP, Esquifino AI, Srinivasan V and Pandi-Perumal SP. 2008. Melatonin and the immune system in aging. Neuroimmunomodulation 15:272–278.
   PubMed Web of Science ®Google Scholar
• Ceraulo L, Ferrugia M, Tesoriere L, Segreto S, Livera MA and Turco Liveri V. 1999. Interactions of melatonin with membrane models: portioning of melatonin in AOT and lecithin reversed micelles. J Pineal Res 26:108–112.
   PubMed Web of Science ®Google Scholar
• Cerutti PA. 1994. Oxy-radicals and cancer. Lancet 344:862–863.
   PubMed Web of Science ®Google Scholar
• Chang HM, Huang YL, Lan CT, Wu UI, Hu ME and Youn SC. 2008. Melatonin preserves superoxide dismutase activity in hypoglossal motoneurons of adult rats following peripheral nerve injury. J Pineal Res 44:172–180.
   Google Scholar
• Chen Z, Chua CC, Gao J, Chau KW, Ho HS, Hamdy RC and Chau BHL. 2009. Prevention of ischemia/reperfusion-induced cardiac apoptosis and injury by melatonin is independent of glutathione peroxidase 1. J Pineal Res 46:235–241.
   PubMed Web of Science ®Google Scholar
• Cheung RTF. 2003. Oxidative damage in the central nervous system: protection by melatonin. Progr Neurobiol 56:359–384.
   Google Scholar
• Clapp-Lilly KL, Smith MA, Perry G, Harris PL, Zhu X and Duffy LK. 2001. Melatonin acts as a pro-oxidant in an organotypic slice culture model of Alzheimer’s disease. Neuroreport 12:1277–1280.
   PubMed Web of Science ®Google Scholar
• Clark IA, Chaudhri G and Cowden WB. 1989. Some roles of free radicals in malaria. Free Radic Biol Med 6:315–321.
   PubMed Web of Science ®Google Scholar
• Conti A, Conconi S, Hertens E, Skwarlo-Sonta KI, Markowska M and Maestroni GJM. 2000. Evidence for melatonin synthesis in mouse and human bone marrow. J Pineal Res 28:193–204.
   PubMed Web of Science ®Google Scholar
• Cuzzocrea S and Reiter RJ. 2001. Pharmacological action of melatonin in shock, inflammation and ischemia/reperfusion injury. Eur J Pharmacol 426:1–10.
   PubMed Web of Science ®Google Scholar
• de Almeida EA, Martinez GR, Klitzke CF, de Medeiros MH and Di Mascio P. 2003. Oxidation of melatonin by singlet oxygen (O2 (1 delta g)) produces N1-acetyl-N2-formyl-5-methoxykynuramine. J Pineal Res 35:131–137.
   Google Scholar
• Dey S, Guha M, Alan A, Goyal M, Binder S, Pal C, Maity P, Mitra K and Bandyopadhyay U. 2009. Malarial infection develops mitochondrial pathology and mitochondrial oxidative stress to promote hepatocyte apoptosis. Free Radic Biol Med 46:271–281.
   Google Scholar
• Dobsak P, Siegelova J, Eicher JC, Jancik J, Svacinova H, Vasku J, Kuchtickova S, Horky M and Wolf JE. 2003. Melatonin protects against ischemia-reperfusion injury and inhibits apoptosis in isolated working rat heart. Pathophysiology 9:179–187.
   PubMedGoogle Scholar
• Dominguez-Rodriguez A, Abreu-Gonzalez P, Garcia-Gonzalez MJ, Kashi JC, Reiter RJ and Jimenez-Sosa A. 2007. A unicenter, randomized, double-blind, parallel-group, placebo-controlled study of Melatonin as an Adjunct in patients with acute myocaRdial Infarction undergoing Angioplasty. The Melatonin Adjunct in the acute myocaRdial Infarction treated with Angioplasty (MARIA) trial: study design and rationale. Contemp Clin Trials 28:532–539.
   PubMed Web of Science ®Google Scholar
• Dominguez-Rodriguez A, Abreu-Gonzalez P, Garcia-Gonzalez MJ, Samimi-Fard S, Kashi JC and Reiter RJ. 2008. Light/dark patterns of soluble vascular cell adhesion molecule-1 in relation to melatonin in patients with ST-segment elevation myocardial infarction. J Pineal Res 44:65–69.
   PubMedGoogle Scholar
• Dubocovich ML and Markowska M. 2005. Functional MT1 and MT2 melatonin receptors in mammals. Endocrine 27:101–110.
   PubMed Web of Science ®Google Scholar
• Ebelt H, Peschke D, Brömme HJ, Mörke W, Blume R and Peschke E. 2000. Influence of melatonin on free radical-induced changes in rat pancreatic beta-cells in vitro. J Pineal Res 28:65–72.
   PubMedGoogle Scholar
• El-Sokkary GH, Reiter RJ, Cuzzocrea S, Caputi AP, Hassanein HF and Tan DX. 1999. Role of melatonin in the reduction of lipid peroxidation and peroxynitrite formation in non-specific shock induced by zymosan. Shock 12:402–408.
   PubMedGoogle Scholar
• Escames G, Guerrero JM, Reiter RJ, Garcia JJ, Munoz-Hoyos A, Ortiz GG and Oh CS. 1997. Melatonin and vitamin E limit nitric oxide-induced lipid peroxidation in rat brain homogenates. Neurosci Lett 230:147–150.
   PubMed Web of Science ®Google Scholar
• Esposito E, Iacono A, Muia C, Crisafulli C, Mattace Raso G, Bramanti P, Meli R and Cuzzocrea S. 2008. Signal transduction pathways involved in protective effects of melatonin in C6 glioma cells. J Pineal Res 44:78–87.
   PubMed Web of Science ®Google Scholar
• Esrefoglu M, Gül M, Ates B, Batcioglu K and Selimoglu MA. 2006. Antioxidant effect of melatonin, ascorbic acid and N-acetylcysteine on caerulein-induced pancreatitis and associated liver injury in rats. World J Gastroenterol 14:259–264.
   Google Scholar
• Fischer TW, Sweatman TW, Semak I, Sayre RM, Wortsman J and Slominski A. 2006. Constitutive and UV-induced metabolism of melatonin in keratinocytes and cell-free systems. FASEB J 20:1564–1566.
   PubMed Web of Science ®Google Scholar
• Fischer TW, Slominski A, Zmijewski MA, Reiter RJ and Paus R. 2008. Melatonin as a major skin protectant: from free radical scavenging to DNA damage repair. Exp Dermatol 17:713–730.
   PubMed Web of Science ®Google Scholar
• Fowler G, Daroszewska M and Ingold KU. 2003. Melatonin does not “directly scavenge hydrogen peroxide”: demise of another myth. Free Radic Biol Med 34:77–83.
   PubMed Web of Science ®Google Scholar
• Fuhrberg B, Hardeland R, Poeggeler B and Behrmann G. 1997. Dramatic rises of melatonn and 5-methoxyyptamine in Gonyaulax exposed to decreased temperature. Biol Rhythm Res 28:144–150.
   Web of Science ®Google Scholar
• Fukutomi J, Fukuda A, Fukuda S, Hara M, Terada A and Yoshida M. 2006. Scavenging activity of indole compounds against ciplatin-induced reactive oxygen species. Life Sci 80:254–257.
   PubMed Web of Science ®Google Scholar
• Fulia F, Gitto E, Cuzzocrea S, Reiter RJ, Dugo L, Gitto P, Barberi S, Cardano S and Barberi I. 2001. Increased levels of malondialdehyde and nitrite/nitrate in the blood of asphyxiated newborns: reduction by melatonin. J Pineal Res 31:343–349.
   PubMed Web of Science ®Google Scholar
• Gilad E, Cuzzocrea S, Zingarella B, Salzman AL and Szabo C. 1997. Melatonin is a scavenger of peroxynitrite. Life Sci 60:PL169–PL174.
   PubMed Web of Science ®Google Scholar
• Gitto E, Reiter RJ, Karbownik M, Tan DX and Barberi I. 2001a. Respiratory distress syndrome in the newborn: role of oxidative stress. Inten Care Med 27:1116–1123.
   PubMed Web of Science ®Google Scholar
• Gitto E, Karbownik M, Reiter RJ, Dugo L, Gitto P, Barberi S, Cardaro S and Barberi I. 2001b. Effects of melatonin treatment in septic newborns. Pediatr Res 50:756–760.
   PubMed Web of Science ®Google Scholar
• Gitto E, Reiter RJ, Karbownik M, Tan DX, Gitto P, Barberi S, Barberi I. 2002. Causes of oxidative stress in the pre- and perinatal period. Biol Neonate 81:146–157.
   PubMedGoogle Scholar
• Gitto E, Reiter RJ, Cardaro SP, La Rosa M, Chiurazzi P, Trimarchi G, Gitto P, Calabro MP and Barberi I. 2004a. Oxidative and inflammatory parameters in respiratory distress syndrome of preterm newborns: beneficial effects of melatonin. Am J Perinatol 21:209–216.
   PubMed Web of Science ®Google Scholar
• Gitto E, Romeo C, Reiter RJ, Impellizzeri P, Pesce S, Basile M, Antonuccio P, Trimarchi G, Gentile C, and Barberi I. 2004b. Melatonin reduces oxidative stress in surgically-treated newborns. J Pediatr Res 39:184–189.
   Google Scholar
• Gitto E, Pellegrino S, Gitto P, Barberi I and Reiter RJ. 2009. Oxidative stress of the newborn in the pre- and postnatal period and the clinical utility of melatonin. J Pineal Res 46:128–139.
   PubMed Web of Science ®Google Scholar
• Giusti P, Franceschini D, Petrone M, Manev H and Floreani M. 1996. In vitro and in vivo protection against kainate-induced excitotoxicity by melatonin. J Pineal Res 20:226–231.
   PubMed Web of Science ®Google Scholar
• Gorfine T and Zisapil N. 2009. Late evening brain activation patterns and their relation to the internal biological time, melatonin, and homeostatic sleep debt. Human Brain Mapp 30:541–552.
   PubMed Web of Science ®Google Scholar
• Guardiola-Le Maitre B. 1997. Toxicology of melatonin. J Biol Rhythms 12:697–706.
   Google Scholar
• Guenther AL, Schmidt SI, Laatsch H, Fotso S, Ness H, Ressmeyer AR, Poeggeler B and Hardeland R. 2005. Reactions of melatonin metabolite AMK (N1-acetyl-5-methoxykynuramine) with reactive nitrogen species: formation of novel compounds, 3-acetamidomethyl-5-methoxycinnolinone and 3-nitro-AMK. J Pineal Res 39:251–260.
   PubMed Web of Science ®Google Scholar
• Guha M, Kumar S, Choubey V, Maity P and Bandyopadhyay U. 2006. Apoptosis in liver during malaria: role of oxidative stress and implication of mitochondrial pathway. FASEB J 20:1224–1226.
   PubMed Web of Science ®Google Scholar
• Guha M, Marty P, Choubey V, Mitra K, Reiter RJ and Bandyopadhyay U. 2007. Melatonin inhibits free radical-mediated mitochondrial-dependent hepatocyte apoptosis and liver damage induced during malarial infection. J Pineal Res 43:372–381.
   PubMed Web of Science ®Google Scholar
• Gultekin F, Delibas N, Yasar S and Kilinc I. 2001. In vivo changes in antioxidant systems and the protective role of melatonin and a combination of vitamin C and vitamin E on oxidative damage in erythrocytes induced by chlorpyrifos-ethyl in rats. Arch Toxicol 75:88–96.
   PubMed Web of Science ®Google Scholar
• Halliwell B. 1997. Antioxidants and human disease: a general introduction. Nutr Rev 55:S44–S49.
   Web of Science ®Google Scholar
• Halliwell B. 2009. The wanderings of a free radical. Free Radic Biol Med 46:531–542.
   PubMed Web of Science ®Google Scholar
• Hardeland R. 2008. Melatonin, hormone of darkness and more: occurrence, control mechanisms, actions and bioactive substances. Cell Mol Life Sci 65:2001–2018.
   PubMed Web of Science ®Google Scholar
• Hardeland R and Pandi-Perumal SR. 2005. Melatonin, a potent agent in antioxidative defense: actions as a natural food constituent, gastrointestinal factor, drug and prodrug. Nutr Metab 2:22–37.
   Google Scholar
• Hardeland R and Poeggeler B. 2003. Non-vertebrate melatonin. J Pineal Res 34:233–241.
   PubMed Web of Science ®Google Scholar
• Hardeland R, Reiter RJ, Poeggeler B and Tan DX. 1993. The significance of the metabolism of the neurohormone melatonin: antioxidative protection and formation of bioactive substances. Neurosci Biobehav Rev 17:347–357.
   PubMed Web of Science ®Google Scholar
• Hardeland R, Balzer I, Poeggeler B, Fuhrberg B, Uria H, Behrmann G, Wolf R, Meyer TJ and Reiter RJ. 1995. On the primary functions of melatonin in evolution: mediation of photoperiodic signals in a unicell, photooxidation, and scavenging of free radicals. J Pineal Res 18:104–111.
   PubMed Web of Science ®Google Scholar
• Hardeland R, Poeggeler B, Niebergall R and Zelasko V. 2003. Oxidation of melatonin by carbonate radicals and chemiluminescence emitted during pyrrole ring cleavage. J Pineal Res 34:17–25.
   PubMed Web of Science ®Google Scholar
• Hardeland R, Pandi-Perumal SR and Cardinali DP. 2006. Melatonin. Int J Biochem Cell Biol 38:313–316.
   PubMed Web of Science ®Google Scholar
• Hevia D, Sainz RM, Blanca D, Quiros I, Tan DX, Rodriguez C, and Mayo JC. 2008. Melatonin uptake in prostate cancer cells: intracellular transport versus simple passive diffusion. J Pineal Res 45:247–257.
   Google Scholar
• Hirata F, Hayaiski O, Tokuyama T and Seno SJ. 1974. In vitro and in vivo formation of two new metabolites of melatonin. J Biol Chem 249:1311–1313.
   PubMed Web of Science ®Google Scholar
• Hoffman RA and Reiter RJ. 1965a. Pineal gland: influence on gonads of male hamsters. Science 148:1609–1611.
   PubMed Web of Science ®Google Scholar
• Hoffman RA and Reiter RJ. 1965b. Influence of compensatory mechanisms and the pineal gland upon light-induced gonadal atrophy in male hamsters. Nature 207:658–659.
   Google Scholar
• Hong RT, Xu JM and Mei Q. 2009. Melatonin ameliorates hepatic fibrosis induced by carbon tetrachloride in rats. World J Gastroenterol 15:1452–1458.
   PubMed Web of Science ®Google Scholar
• Hosseinimehr SJ. 2007. Trends in the development of radioprotective agents. Drug Discov Today 12:794–805.
   PubMed Web of Science ®Google Scholar
• Ishizuka B, Kuribayashi Y, Murai K, Amemiya A and Itoh MT. 2000. The effect of melatonin on in vitro fertilization and embryo development. J Pineal Res 28:48–51.
   PubMed Web of Science ®Google Scholar
• Itoh MP, Ishizuka B, Kuribayashi Y, Amemiya A and Sumi Y. 1999. Melatonin, its precursors, and synthesizing enzymes in the human ovary. Mol Human Reprod 5:402–408.
   PubMed Web of Science ®Google Scholar
• Itoh MT, Takahashi N, Abe M and Shimizu K. 2007. Expression and cellular localization of melatonin-synthesizing enzymes in the rat lens. J Pineal Res 42:92–96.
   PubMed Web of Science ®Google Scholar
• Jahnke G, Marr M, Myers C, Wilson R, Travalos G and Price C. 1999. Maternal and developmental toxicity evaluation of melatonin administered orally to pregnant Sprague-Dawley rats. Toxicol Sci 50:271–279.
   PubMed Web of Science ®Google Scholar
• Jan JE, Wasdell MB, Freeman RD and Bax M. 2007. Evidence supporting the use of melatonin in short gestation infants. J Pineal Res 42:22–27.
   PubMed Web of Science ®Google Scholar
• Jan JE, Reiter RJ, Wasdell MB and Bax M. 2009. The role of thalamus in sleep, pineal melatonin production, and circadian rhythm sleep disorders. J Pineal Res 46:1–7.
   PubMed Web of Science ®Google Scholar
• Jou MJ, Jou SB, Chen HM, Lin CH and Peng TI. 2002. Critical role of mitochondrial reactive oxygen species formation in visible laser irradiation-induced apoptosis in rat brain astrocytes (RBA-1). J Biomed Sci 9:507–518.
   Google Scholar
• Jou MJ, Peng TI, Reiter RJ, Jou SB, Wu HY and Wen ST. 2004. Visualization of the antioxidative effects of melatonin at the mitochondrial level during oxidative stress induced apoptosis of rat brain astrocytes. J Pineal Res 37:55–70.
   PubMed Web of Science ®Google Scholar
• Jou MJ, Peng TI, Yu PZ, Jou SB, Reiter RJ, Chen JY, Wu HY, Chen CC and Hsu LF. 2007. Melatonin protects against common deletion of mitochondrial DNA-augmented mitochondrial oxidative stress and apoptosis. J Pineal Res 43:389–403.
   PubMed Web of Science ®Google Scholar
• Kaneko S, Okumura K, Numaguchi Y, Matsiu H, Murase K, Mokuno S, Morishima I, Hira K, Toki Y, Ito T, and Hayakawa T. 2000. Melatonin scavenges hydroxyl radical and protects isolated rat hearts from ischemic reperfusion injury. Life Sci 67:101–112.
   Web of Science ®Google Scholar
• Kara H, Cevik A, Konar V, Dayangac A and Servi K. 2008. Effect of selenium with vitamin E and melatonin on cadmuin-induced oxidative damage in rat liver and kidneys. Biol Trace Elem Res 125:236–244.
   Google Scholar
• Karbownik M and Reiter RJ. 2000. Antioxidative effects of melatonin in protection against cellular damage caused by ionizing radiation. Proc Soc Exp Biol Med 225:9–22.
   PubMed Web of Science ®Google Scholar
• Karbownik M, Reiter RJ, Qi W, Garcia JJ, Tan DX, Manchester LC, and Vijayalaxmi 2000. Protective effects of melatonin against oxidation of guanine bases in DNA and deceased microsomal membrane fluidity in rat liver induced by whole body ionizing radiation. Mol Cell Biochem 211:137–144.
   PubMed Web of Science ®Google Scholar
• Khansari N, Shakiba Y and Mahmoudi M. 2009. Chronic inflammation and oxidative stress as a major cause of age-related diseases and cancer. Rec Patents Inflamm Allergy Drug Discov 3:73–80.
   PubMedGoogle Scholar
• King TS and Steinlechner S. 1985. Pineal indolalkylamine synthesis and metabolism: kinetic considerations. Pineal Res Rev 3:69–114.
   Google Scholar
• Kitay JI and Altschule MD. 1954. The Pineal Gland. Cambridge, MA: Harvard University Press.
   Google Scholar
• Koh PO. 2008. Melatonin attenuates the focal ischemia injury by inhibiting the dissociation of pBad from 14-3-3. J Pineal Res 44:101–106.
   PubMed Web of Science ®Google Scholar
• Koppisetti S, Jenigiri B, Terron MP, Tengattini S, Tamura H, Flores LJ, Tan DX and Reiter RJ. 2008. Reactive oxygen species and the hypomobility of the gallbladder as targets for the treatment of gallstones with melatonin: a review. Dig Dis Sci 53:2592–2603.
   Google Scholar
• Korkmaz A, Topal T, Oter S, Tan DX and Reiter RJ. 2008. Hyperglycemia-related pathophysiologic mechanisms and potential beneficial actions of melatonin. Mini-Rev Med Chem 8:1144–1153.
   PubMedGoogle Scholar
• Korkmaz A, Sanchez-Barcelo E, Tan DX and Reiter RJ. 2009a. Role of melatonin in the epigenetic regulation of breast cancer. Breast Cancer Res Treat, 115:13–27.
   PubMed Web of Science ®Google Scholar
• Korkmaz A, Reiter RJ, Topal T, Manchester LC, Oter S and Tan DX. 2009b. Melatonin: an established antioxidant worthy of use in clinical trials. Mol Med 15:43–50.
   PubMed Web of Science ®Google Scholar
• Kouvaris JR, Kouloulias VL and Vlahos LJ. 2007. Amifostine: the first selective-target and broad-spectrum radioprotector. Oncologist 12:738–747.
   PubMed Web of Science ®Google Scholar
• Kucukakin B, Lykkesfeldt J, Nielsen JJ, Reiter RJ, Rosenburg J and Gogenur I. 2008. Utility of melatonin to treat surgical stress after major vascular surgery – a safety study. J Pineal Res 44:426–431.
   PubMed Web of Science ®Google Scholar
• Kurokawa Y, Hayashi Y, Mackawa A, Takahashi M, Kokubo T and Odashima S. 1983. Carcinogenicity of potassium bromate administered orally to F344 rats. J Natl Cancer Inst 71:965–972.
   PubMed Web of Science ®Google Scholar
• Kvetnoy I. 2002. Extrapineal melatonin in pathology: new perspectives for diagnosis, prognosis and treatment of illness. Neuroendocr Lett 23 (suppl. 1):92–96.
   Google Scholar
• Lagneux C, Joyeux M, Demenge P, Ribuot C and Godin-Ribuot D. 2000. Protective effects of melatonin against ischemia-reperfusion injury in the isolated rat heart. Life Sci 66:603–609.
   Google Scholar
• Lee YM, Chen HR, Hsaao G, Shou JR, Wang JJ and Yen MH. 2002. Protective effects of melatonin on myocardial ischemia/reperfusion injury in vivo. J Pineal Res 33:72–80.
   PubMed Web of Science ®Google Scholar
• Leon J, Acuna-Castroviejo D, Saenz RM, Mayo JC, Tan DX and Reiter RJ. 2004. Melatonin and mitochondrial function. Life Sci 75:765–790.
   PubMed Web of Science ®Google Scholar
• Leon J, Acuna-Castroviejo D, Escames G, Tan DX and Reiter RJ. 2005. Melatonin mitigates mitochondrial malfunction. J Pineal Res 38:1–9.
   PubMed Web of Science ®Google Scholar
• Leon J, Escames G, Rodriguez MI, Lopez LC, Tapias V, Enterna A, Camacho E, Carrion MD, Gallo MA, Espinosa A, Tan DX, Reiter RJ, and Acuna-Castroviejo D. 2006. Inhibition of neuronal nitric oxide synthase activity by N1-acetyl-5-methoxykynuramine, a brain metabolite of melatonin. J Neurochem 98:2023–2033.
   PubMed Web of Science ®Google Scholar
• Lerner AB and Wright RM. 1960. In vitro frog skin assay for agents that darken and lighten melanocytes. Meth Biochem Anal 8:295–307.
   PubMedGoogle Scholar
• Lerner AB, Case JD, Takahashi Y, Lee Y and Mori W. 1958. Isolation of melatonin, the pineal gland factor that lightens melanocytes. J Amer Chem Soc 80:2587.
   Web of Science ®Google Scholar
• Lerner AB, Case JD and Heinzelmann RV. 1959a. Structure of melatonin. J Amer Chem Soc 81:6084–6085.
   Web of Science ®Google Scholar
• Lerner AB, Case JD, Mori W and Wright MR. 1959b. Melatonin in peripheral nerve. Nature 27:1826.
   Google Scholar
• Lerner AB, Case JD and Takahashi Y. 1960. Isolation of melatonin and 5-methoxyindole-3-acetic acid from bovine pineal gland. J Biol Chem 235:1992–1997.
   PubMed Web of Science ®Google Scholar
• Li XJ, Gu J, Lu SD and Sun FY. 2002. Melatonin attenuates MPTP-induced dopaminergic neuronal injury associated with scavenging hydroxyl radicals. J Pineal Res 32:47–52.
   Google Scholar
• Li ZR, Reiter RJ, Fujimori O, Ho CS and Duan YP. 1997. Cataractogenesis and lipid peroxidation in newborn rats treated with buthionine-sulfoximine: prevented actions of melatonin. J Pineal Res 22:117–123.
   PubMed Web of Science ®Google Scholar
• Liepnitz G, Solano AF, Seminotti B, Amaral AU, Fernandes CG, Beskow AP, Dutro Filho CS and Weiner M. 2009. Glycine provokes lipid oxidative damage and reduces the antioxidant defenses in brain cortex of young rats. Cell Mol Neurobiol 29:253–261.
   Google Scholar
• Lincoln GA, Andersonn H and Loudon A. 2003. Clock genes in calendar cells as the basis of annual timekeeping in mammals – a unifying hypothesis. J Endocrinol 79:1–13.
   Google Scholar
• Livrea MA, Tesoriere L, D’Arpa D and Morreale M. 1997. Reaction of melatonin with hydroxyl radicals in phospholipid bilayers. Free Radic Biol Med 5:706–711.
   Google Scholar
• Lopez-Burillo S, Tan DX, Mayo JC, Sainz RM, Manchester LC and Reiter RJ. 2003. Melatonin, xanthurenic acid, resveratrol, EGCG, vitamin C and alpha-lipoic acid differentially reduce oxidative DNA damage induced by Fenton reagents: a study of their individual and synergistic actions. J Pineal Res 34:269–277.
   PubMed Web of Science ®Google Scholar
• Ma X, Idle JR, Krauez KW, Tan DX, Ceraulo L and Gonzalez FJ. 2006. Urinary metabolites and antioxidant products of exogenous melatonin in the mouse. J Pineal Res 40:343–349.
   PubMed Web of Science ®Google Scholar
• Mahal HS, Sharma HS and Mukerjee T. 1999. Antioxidant properties of melatonin: a pulse radiolysis study. Free Radic Biol Med 26:557–565.
   PubMed Web of Science ®Google Scholar
• Maldonado MD, Murrillo-Cabezas F, Calvo JR, Lardone PJ, Tan DX, Guerrero JM and Reiter RJ. 2007. Melatonin as pharmacologic support in burn patients: a proposed solution to thermal injury-related lymphocytopenia and oxidative damage. Crit. Care Med. 35:1177–1185.
   Web of Science ®Google Scholar
• Maldonado MD, Perez-San-Gregorio MA and Reiter RJ. 2009. The role of melatonin in the immune-neuro-psychology of mental disorders. Rec Patents CNS Drug Disc 4:61–69.
   PubMedGoogle Scholar
• Manchester LC, Poeggeler B, Alvarez FL, Ogden GB and Reiter RJ. 1995. Melatonin immunoreactivity in the prokaryote Rhodospirillum rubrum: implications for an ancient antioxidant system. Cell Mol Biol Res 41:391–395.
   PubMedGoogle Scholar
• Manda K, Ueno M and Anzai K. 2007. AFMK, a melatonin metabolite, attenuates x-ray induced oxidation damage to DNA, proteins and lipids in mice. J Pineal Res 42:386–393.
   PubMed Web of Science ®Google Scholar
• Manda K, Ueno M and Anzai K. 2008. Melatonin mitigates oxidative damage and apoptosis in mouse cerebellum by high-LET 56Fe particle irradiation. J Pineal Res 44:189–196.
   PubMed Web of Science ®Google Scholar
• Mansouri A, Demeilliers C, Amsellem S, Pessayre D and Fromenty B. 2001. Acute ethanol administration oxidatively damages and depletes mitochondrial DNA in mouse liver, brain, heart, and skeletal muscle: protective effects of melatonin. J Pharmacol Exp Ther 298:737–743.
   PubMed Web of Science ®Google Scholar
• Markowska M, Bentkowski P, Kloc M and Pijanowska J. 2009. Presence of melatonin in Daphnia magna. J Pineal Res 46:242–243.
   PubMed Web of Science ®Google Scholar
• Marshall KA, Reiter RJ, Poeggeler B, Aruoma OI and Halliwell B. 1996. Evaluation of the antioxidant activity of melatonin in vitro. Free Radic Biol Med 21:307–315.
   PubMed Web of Science ®Google Scholar
• Martin MJ, Macias M, Escames G, Leon J and Acuna-Castroviejo D. 2000a. Melatonin but not vitamins C and E maintains glutathione homeostasis in t-butyl-hydroperoxide-induced mitochondrial oxidative stress. FASEB J 14:1677–1679.
   PubMed Web of Science ®Google Scholar
• Martin MJ, Macias M, Escames G, Reiter RJ, Agapito MP, Ortiz GG and Acuna-Castroviejo D. 2000b. Melatonin induced increased activity of the respiratory chain complexes I and IV can prevent mitochondrial damage induced by ruthenium red in vivo. J Pineal Res 28:193–248.
   Google Scholar
• Martinez-Cruz F, Pozo D, Osuna C, Espinar A, Merchante C and Guerrero JM. 2002. Oxidative stress induced by phenylketonuria in the rat: prevention by melatonin, vitamin E and vitamin C. J Neurosci Res 69:550–558.
   PubMed Web of Science ®Google Scholar
• Martinez-Cruz F, Osuna C and Guerrero JM. 2006. Mitochondrial damage induced by fetal hyperphenylalaninemia in the rat brain and liver: its prevention by melatonin, vitamin E and vitamin C. Neurosci Lett 392:1–4.
   PubMed Web of Science ®Google Scholar
• Masson-Pevet M. 2007. Melatonin in the circadian system (in French). J Soc Biol 201:77–83.
   PubMedGoogle Scholar
• Matuszak Z, Reszka K and Chignell CF. 1997. Reaction of melatonin and related indoles with hydroxyl radicals: EPR and spin trapping investigations. Free Radic Biol Med 23:367–372.
   PubMed Web of Science ®Google Scholar
• Matuszak Z, Bilska MA, Reszka KJ, Chignell CF and Bilski P. 2003. Interaction of singlet molecular oxygen with melatonin and related indoles. Photochem Photobiol 78:449–455.
   PubMed Web of Science ®Google Scholar
• McCord CP and Allen FB. 1917. Evidence associating pineal gland function with alterations in pigmentation. J Exp Zool 23:207–224.
   Google Scholar
• Melchiorri D, Reiter RJ, Attia AM, Hara M, Burgos A and Nistico G. 1994. Potent protective effect of melatonin on in vivo paraquat-induced oxidative damage in rats. Life Sci 56:83–89.
   Google Scholar
• Messner M, Huether G, Lorf T, Ramadori G and Schwörer H. 2001. Presence of melatonin in the human hepatobiliary- gastrointestinal tract. Life Sci 69:543–551.
   PubMed Web of Science ®Google Scholar
• Mogler KH. 1958. Das Endokrine System des Syrischen Goldhamster unter Beriicksichtigung des Natürlichen und Experimentellen Winterschlöf. Z Morphol Okeol Tiere 47:267–308.
   Google Scholar
• Monobe M, Hino M, Sumi M, Uzawa A, Hirayama R, Ando K, Kojima J. 2005. Protective effects of melatonin on gamma-ray induced intestinal damage. Int J Radiat Biol 81:855–860.
   PubMed Web of Science ®Google Scholar
• Montilla P, Cruz A, Padillo FJ, Tunez I, Gascon F, Munoz MC, Gomez M and Pera C. 2001. Melatonin versus vitamin E as protective treatment against oxidative stress after extra-hepatic bile duct ligation in rats. J Pineal Res 31:138–144.
   PubMed Web of Science ®Google Scholar
• Nesic O, Lee J, Unabia GC, Johnson K, Ye Z, Vergara L, Hulsebosch CE and Perez-Polo JR. 2008. Aquaporin 1 – a novel player in spinal cord injury. J Neurochem 105:628–640.
   PubMed Web of Science ®Google Scholar
• Noda Y, Mori A, Liburty R and Packer L. 1999. Melatonin and its precursor scavenge nitric oxide. J Pineal Res 27:159–163.
   PubMed Web of Science ®Google Scholar
• Okatani Y, Okamoto K, Hayashi K, Wakatsuki A, Tamura S and Sagara V. 1998. Maternal-fetal transfer of melatonin in pregnant women near term. J Pineal Res 25:129–134.
   PubMed Web of Science ®Google Scholar
• Osseni RA, Rat P, Bogdan A, Warnet JM and Touitov Y. 2000. Evidence of a pro-oxidant and antioxidant action of melatonin on human liver cell line HepG2. Life Sci 68:387–399.
   PubMed Web of Science ®Google Scholar
• Pablos MI, Agapito MT, Guiterrez R, Recio JM, Reiter RJ, Barlow-Walden LR, Acuna-Castroviejo D and Menendez-Pelaez A. 1995. Melatonin stimulates the activity of the detoxifying enzyme glutathione peroxidase in several tissues of chicks. J Pineal Res 19:111–115.
   PubMed Web of Science ®Google Scholar
• Pacher P, Beckman JS and Liaudet L. 2007. Nitric oxide and peroxynitrite in health and disease. Physiol Rev 87:315–424.
   PubMed Web of Science ®Google Scholar
• Pandi-Perumal SR, Srinivasan V, Maestroni GJ, Cardinali DP, Poeggeler B and Hardeland R. 2006. Melatonin: nature’s most versatile biological signal? FEBS J 273:2813–2838.
   PubMed Web of Science ®Google Scholar
• Pang SF and Allen AE. 1986. Extra-pineal melatonin in the retina: its regulation and physiological function. Pineal Res Rev 4:55–96.
   Google Scholar
• Pappolla MA, Chyan YJ, Poeggeler B, Frangione B, Wilson G, Ghiso J and Reiter RJ. 2000. An assessment of the antioxidant and the antiamyloidogenic properties of melatonin: implications for Alzheimer’s disease. J Neural Transm 107:203–231.
   PubMed Web of Science ®Google Scholar
• Paul S, Sharma AV, Mahapatra PD, Bhattacharya M, Reiter RJ and Swarnakar S. 2008. Role of melatonin in regulating matrix metalloproteinase-9 via tissue inhibitors of metalloproteinase-1 during protection against endometriosis. J Pineal Res 44:439–449.
   PubMed Web of Science ®Google Scholar
• Peschke E. 2008. Melatonin, endocrine pancreas and diabetes. J Pineal Res 44:26–40.
   PubMed Web of Science ®Google Scholar
• Peyrot F and Ducrocq C. 2008. Potential role of tryptophan derivatives in stress responses characterized by the generation of reactive oxygen and reactive nitrogen species. J Pineal Res 45:235–246.
   PubMed Web of Science ®Google Scholar
• Peyrot F, Martin MT, Migault J and Ducrocq C. 2003. Reactivity of peroxynitrite with melatonin as a function of pH and CO2 content. Eur J Org Chem 1:172–181.
   Google Scholar
• Pieri C, Marra M, Moroni F, Recchioni R and Marcheselli F. 1994. Melatonin: a peroxyl radical more effective than vitamin E. Life Sci 55:PL271–PL276.
   PubMed Web of Science ®Google Scholar
• Poeggeler B. 2005. Melatonin, aging and age-related diseases: perspectives for prevention, intervention, and therapy. Endocrine 27:201–212.
   PubMedGoogle Scholar
• Pozo D, Reiter RJ, Calvo JR and Guerrero JM. 1994. Physiological concentrations of melatonin inhibit nitric oxide synthase in rat cerebellum. Life Sci 55:PL455–PL460.
   PubMed Web of Science ®Google Scholar
• Pozo D, Reiter RJ, Calvo JR and Guerrero JM. 1997. Inhibitor of cerebellar nitric oxide synthase and cyclic GMP production by melatonin via complex formation with calmodulin. J Cell Biochem 65:430–442.
   PubMed Web of Science ®Google Scholar
• Qi W, Reiter RJ, Tan DX, Manchester LC, Siu AW and Garcia JJ. 2000a. Increased levels of damaged DNA induced by chromium (III) and H2O2: protection by melatonin and related molecules. J Pineal Res 29:54–61.
   PubMed Web of Science ®Google Scholar
• Qi W, Reiter RJ, Tan DX, Garcia JJ, Manchester LC, Karbownik M and Calvo JR. 2000b. Chromium (III)-induced 8- hydroxydeoxyguanosine in DNA and its reduction by antioxidants: comparative efforts of melatonin, ascorbate and vitamin E. Environ Health Perspect 108:399–402.
   PubMed Web of Science ®Google Scholar
• Qi W, Reiter RJ, Tan DX, Manchester LC and Calvo JR. 2001. Melatonin prevents δ-aminolevulinic acid-induced oxidative DNA damage in the presence of Fe2+. Mol Cell Biochem 218:87–92.
   Google Scholar
• Quay WB. 1956. Volumetric and cytologic variation in the pineal body of Peromyscus leucopus (Rodentia) with respect to sex, captivity and daylength. J Morphol 98:471–475.
   Google Scholar
• Quay WB. 1964. Circadian and estrous rhythms in pineal melatonin and 5-hydroxyindole-3- acetic acid. Proc Soc Exp Biol Med 115:710–713.
   PubMed Web of Science ®Google Scholar
• Reiter RJ. 1973a. Pineal control of a seasonal reproductive rhythm in male golden hamsters exposed to natural daylight and temperature. Endocrinology 92:423–430.
   PubMed Web of Science ®Google Scholar
• Reiter RJ. 1973b. Comparative physiology: pineal gland. Annu Rev Physiol 35:305–328.
   PubMed Web of Science ®Google Scholar
• Reiter RJ. 1974. Circannual reproductive rhythms in mammals related to photoperiod and pineal function. Chronobiologia 1:365–395.
   PubMedGoogle Scholar
• Reiter RJ. 1991. Melatonin: the chemical expression of darkness. Mol Cell Endocrinol 79:C153–C158.
   PubMed Web of Science ®Google Scholar
• Reiter RJ. 1995. Oxidative processes and antioxidative defense mechanisms in the aging brain. FASEB J 9:526–533.
   PubMed Web of Science ®Google Scholar
• Reiter RJ. 1998. Oxidative damage in the central nervous system: protection by melatonin. Progr Neurobiol 56:359–384.
   PubMed Web of Science ®Google Scholar
• Reiter RJ. and Hester RJ. 1966. Interrelationships of the pineal gland, the superior cervical ganglia and the photoperiod in the regulation of the endocrine systems of hamsters. Endocrinology 79:1168–1170.
   Google Scholar
• Reiter RJ and Korkmaz A. 2008. Clinical aspects of melatonin. Saudi Med J 29:1537–1547.
   PubMed Web of Science ®Google Scholar
• Reiter RJ and Tan DX. 2003. What constitutes a physiological concentration of melatonin? J Pineal Res 34:79–80.
   PubMed Web of Science ®Google Scholar
• Reiter RJ, Tan DX, Osuna C and Gitto E. 2000. Actions of melatonin in the reduction of oxidative stress: a review. J Biomed Res 7:444–458.
   Google Scholar
• Reiter RJ, Tan DX, Manchester LC and Qi W. 2001. Biochemical reactivity of melatonin with reactive oxygen and nitrogen species: a review of the evidence. Cell Biochem Biophys 34:237–246.
   PubMed Web of Science ®Google Scholar
• Reiter RJ, Tan DX, Manchester LC, Lopez-Burillo S, Sainz RM and Mayo JC. 2003. Melatonin: detoxification of oxygen and nitrogen-based reactants. Adv Exp Med Biol 527:539–548.
   PubMed Web of Science ®Google Scholar
• Reiter RJ, Tan DX and Pappolla MA. 2004. Melatonin relieves the neural oxidative burden that contributes to dementias. Ann NY Acad Sci 1035:179–195.
   PubMed Web of Science ®Google Scholar
• Reiter RJ, Tan DX, Leon J, Kilic U and Kilic E. 2005a. When melatonin gets on your nerves: its beneficial actions in experimental models of stroke. Exp Biol Med 230:104–117.
   PubMed Web of Science ®Google Scholar
• Reiter RJ, Manchester LC and Tan DX. 2005b. Melatonin in walnuts: influence on levels of melatonin and total antioxidant capacity of blood. Nutrition 21:920–924.
   PubMed Web of Science ®Google Scholar
• Reiter RJ, Tan DX and Maldonado MD. 2005c. Melatonin as an antioxidant: physiology versus pharmacology. J Pineal Res 39:215–216.
   PubMed Web of Science ®Google Scholar
• Reiter RJ, Tan DX, Jou MJ, Korkmaz A, Manchester LC and Paredes SD. 2008a. Biogenic amines in the reduction of oxidative stress: melatonin and its metabolites. Neuroendocrinol Lett 29:391–398.
   PubMed Web of Science ®Google Scholar
• Reiter RJ, Paredes S, Korkmaz A, Jou MJ and Tan DX. 2008b. Melatonin combats molecular terrorism at the mitochondrial level. Interdisc Toxicol 1:137–149.
   PubMedGoogle Scholar
• Reiter RJ, Paredes SD, Korkmaz A, Manchester LC and Tan DX. 2008c. Melatonin in relation to the “strong” and “weak” versions of the free radical theory of aging. Adv Med Sci 53:1–11.
   Google Scholar
• Rodriquez C, Mayo JC, Sainz RM, Antolin I, Herrera F, Martin V and Reiter RJ. 2004. Regulation of antioxidant enzymes: a significant role for melatonin. J Pineal Res 36:1–9.
   PubMedGoogle Scholar
• Rosales-Corral S, Tan DX, Reiter RJ, Valdivia-Velazquez M, Martinez-Barboza G, Acosta-Martinez JP and Ortiz GG. 2003. Orally administered melatonin reduces oxidative stress and proinflammatory cytokines induced by amyloid-β peptide in rat brain: a comparative, in vivo study versus vitamin C and E. J Pineal Res 35:80–84.
   PubMed Web of Science ®Google Scholar
• Rosen J, Than NN, Koch D, Poeggeler B, Laatsch H and Hardeland R. 2006. Interactions of melatonin and its metabolites with ABTS cation radical: extension of the radical scavenger cascade and formation of a novel class of oxidation products, C2-substituted 3-indolinones. J Pineal Res 41:374–381.
   PubMed Web of Science ®Google Scholar
• Ross R. 1999. Atherosclerosis – an inflammatory disease. N Engl J Med 340:115–126.
   PubMed Web of Science ®Google Scholar
• Rozov SV, Filatova EV, Orlov AA, Volkova AV, Zhloba ARA, Blashko EL and Pozdeyev NV. 2003. N1-acetyl-N2-formyl-5-methoxykynuramine is a product of melatonin oxidation in rats. J Pineal Res 35:245–250.
   Google Scholar
• Sadir S, Deveci S, Korkmaz A and Oter S. 2007. Alpha-tocopherol, beta-carotene and melatonin administration protects cyclophosphamide-induced oxidative damage in bladder tissue of rats. Cell Biochem Funct 25:521–526.
   Web of Science ®Google Scholar
• Sahna E, Olimez E and Acet A. 2002. Effects of physiological and pharmacological concentrations of melatonin on ischemia-reperfusion arrhythmias in rats: can the incidence of sudden cardiac death be reduced? J Pineal Res 32:194–198.
   PubMed Web of Science ®Google Scholar
• Sahna E, Parkohpinar H, Ozer MK, Ozturk F, Ozugurlu F and Acet A. 2003. Melatonin protects against myocardial doxorubicin toxicity in rats: role of physiologic concentrations. J Pineal Res 35:357–361.
   Google Scholar
• Sai K, Takagi A, Umemura T, Hasegawa R and Kurokawa Y. 1991. Relation of 8-hydroxydeoxyguanosine formation in rat kidney to lipid peroxidation, glutathione level and relative organ weight after a single administration of potassium bromate. Jpn J Cancer 82:165–169.
   PubMedGoogle Scholar
• Samantaray S, Sribnick EA, Das A, Knaryan VH, Matzelle DD, Yallapragada AV, Reiter RJ, Ray SK and Banik N. 2008. Melatonin attenuates calpain upregulation; axonal damage and neuronal death in spinal cord injury in rats. J Pineal Res 44:348–357.
   PubMed Web of Science ®Google Scholar
• Sener G, Sehirli AO and Ayanoglu-Dulger G. 2003. Protective effect of melatonin, vitamin E and N-acetylcysteine against acetaminophen toxicity in mice: a comparative study. J Pineal Res 35:61–68.
   PubMed Web of Science ®Google Scholar
• Sewerynek E, Melchiorri D, Reiter RJ, Ortiz GG and Lewinski A. 1995a. Lipopolysaccharide-induced hepototoxicity is inhibited by the antioxidant melatonin. Eur J Pharmacol 293:327–334.
   PubMedGoogle Scholar
• Sewerynek E, Melchiorri D, Chen L and Reiter RJ. 1995b. Melatonin reduces both basal and bacterial lipopolysaccharide-induced lipid peroxidation in rats. Free Radic Biol Med 19:903–909.
   PubMed Web of Science ®Google Scholar
• Sharma S and Haldar C. 2009. Comparative effect of melatonin and vitamin E on phenylhydrazine-induced toxicity in the spleen of Funambulus pennanti. Environ Toxicol 24:1–9.
   Google Scholar
• Shirazi A, Ghobadi G and Ghazi-Khanasari M. 2007. A radiobiological review on melatonin: a novel radioprotecor. J Radiat Res (Tokyo) 48:263–272.
   PubMed Web of Science ®Google Scholar
• Shiu SYW. 2007. Towards rational and evidence-based use of melatonin in prostate cancer prevention and treatment. J Pineal Res 43:1–9.
   Google Scholar
• Siddiqi NJ and Pandey VC. 1999. Studies on hepatic oxidative stress and antioxidative defense systems during arteether treatment of Plasmodium yoelii nigeriensis infected mice. Mol Cell Biochem 196:169–173.
   PubMed Web of Science ®Google Scholar
• Silva SO, Ximenes VF, Catalani IH and Campa A. 2000. Myeloperoxidase-catalyzed oxidation of melatonin by activated neutrophils. Biochem Biophys Res Commun 279:657–662.
   Google Scholar
• Silva SO, Rodrigues MR, Carvalho SR, Catalani LH, Campo A and Ximenes VF. 2004. Oxidation of melatonin and its catabolites, N1-acetyl-N2-formyl-5-methoxykynuramine and N1-acetyl-5-methoxykynuramine by activated leucocytes. J Pineal Res 37:171–175.
   PubMed Web of Science ®Google Scholar
• Simko F. and Paulis L. 2007. Melatonin as a potent antihypertensive treatment. J Pineal Res 42:319–322.
   PubMed Web of Science ®Google Scholar
• Siu AW, Maldonado MD, Sanchez-Hidalgo M, Tan DX and Reiter RJ. 2006. Potential effects of melatonin in experimental free radical-related ocular diseases. J Pineal Res 40:101–109.
   PubMed Web of Science ®Google Scholar
• Siwicka A, Reiter RJ, Tan DX, Wojtasiewicz KI, Leniewski A, Maurin JK, Blachot D and Czarnocki Z. 2004. The structure of NO-diacetyl derivative of cyclic 3-hydroxymelatonin is unambiguously proven. Centr Eur J Chem 2:425–433.
   Google Scholar
• Siwicka A, Moleda Z, Wojtasiewicz K, Zawadzka A, Maurin JK, Panasiewicz M, Pacuszka T and Czarnocki Z. 2008. The oxidation products of melatonin derivatives exhibit acetylcholinesterase and butyrylcholinesterase inhibiting activity. J Pineal Res 45:40–49.
   Google Scholar
• Skinner DC and Malpaux B. 1999. High melatonin concentrations in the third ventricular cerebrospinal fluid are not due to Galen vein blood recirculating through the choroid plexus. Endocrinology 14:4399–4405.
   Google Scholar
• Slominski A, Baker J, Rosano TG, Guisti LW, Ermak G, Grande M and Gaudet SJ. 1996. Metabolism of serotonin, to N-acetylserotonin, melatonin and 5-methoxytryptamine in hamster skin. J Biol Chem 271:12281–12286.
   PubMed Web of Science ®Google Scholar
• Slominski A, Pisarchik A, Semak I, Sweatman T, Wortsman J, Szczesniewski A, Slugocki G, McNulty J, Kauser S, Tobin DJ, Jing C, and Johansson O. 2002. Serotoninergic and melatoninergic systems are fully expressed in human skin. FASEB J 16:896–898.
   PubMed Web of Science ®Google Scholar
• Slominski A, Tobin DJ, Zmijewski MA, Wortsman J and Paus R. 2007. Melatonin in skin: synthesis, metabolism and functions. Trends Endocrinol Metab 19:17–24.
   Google Scholar
• Sofic E, Rimpapa Z, Kundurovic Z, Sapcanin A, Tahirovic I, Rustembegovic A and Gao G. 2005. Antioxidant capacity of the neurohormone melatonin. J Neural Transm 112:349–358.
   Google Scholar
• Spector A and Garner WH., 1981. Hydrogen peroxide and human cataract. Exp Eye Res 33:673–681.
   PubMed Web of Science ®Google Scholar
• Starkov AA. 2008. The role of mitochondria in reactive oxygen species metabolism and signaling. Ann NY Acad Sci 1147:37–52.
   PubMed Web of Science ®Google Scholar
• Stasica P, Ulanski P and Rosiak JM. 1998. Melatonin as a hydroxyl radical scavenger. J Pineal Res 25:65–66.
   PubMed Web of Science ®Google Scholar
• Stasica P, Paneth P and Rosiak JM. 2000. Hydroxyl radical reaction with melatonin molecule: a computational study. J Pineal Res 29:125–127.
   PubMed Web of Science ®Google Scholar
• Stefulj J, Hörtner M, Ghosh M, Schavenstein I, Rinner I, Wölfier A, Semmler J and Liebmann PM. 2001. Gene expression of the key enzymes of melatonin synthesis in extrapineal tissues of the rat. J Pineal Res 30:243–247.
   PubMed Web of Science ®Google Scholar
• Tamarkin L, Baird CJ and Almeida OF. 1985. Melatonin: a coordinating signal for mammalian reproduction. Science 227:714–720.
   PubMed Web of Science ®Google Scholar
• Tamura H, Nakamura Y, Terron MP, Flores LJ, Manchester LC, Tan DX, Sugino N and Reiter RJ. 2008a. Melatonin and pregnancy in the human. Reprod Toxicol 25:291–303.
   PubMed Web of Science ®Google Scholar
• Tamura H, Takasaki A, Miwa I, Taniguchi K, Maekawa R, Asada H, Taketani T, Matsuoka A, Yamagata Y, Shimamura L. Morioka H, Ishikawa H, Reiter RJ, and Sugino N. 2008b. Oxidative stress impairs oocyte quality and melatonin protects oocytes from free radical damage and improves fertilization rate. J Pineal Res 44:280–287.
   PubMed Web of Science ®Google Scholar
• Tamura H, Nakamura Y, Korkmaz A, Manchester LC, Tan DX, Sugino N and Reiter RJ. 2009. Melatonin and the ovary: physiology and pathophysiological implications. Fertil Steril, in press.
   Google Scholar
• Tan DX, Chen LD, Poeggeler B, Manchester LC and Reiter RJ. 1993. Melatonin: a potent, endogenous hydroxyl radical scavenger. Endocrine J 1:57–60.
   Google Scholar
• Tan DX, Reiter RJ and Chen LD. 1994. Both physiological and pharmacological level of melatonin reduce DNA adduct formation induced by the carcinogen safrole. Carcinogenesis 15: 215–218.
   PubMed Web of Science ®Google Scholar
• Tan DX, Manchester LC, Reiter RJ, Plummer BF, Hardies LJ, Weintraub ST, Vijayalaxmi and Shepherd AMM. 1998a. A novel melatonin metabolite, cyclic 3-hydroxymelatonin, and biomarker of in vivo hydroxyl radical generation. Biochem Biophys Res Commun 253:614–620.
   PubMed Web of Science ®Google Scholar
• Tan DX, Manchester LC, Reiter RJ, Qi W, Kim SJ and El-Sokkary GH. 1998b. Ischemia/reperfusion-induced arrhythmias in isolated rat heart: prevention my melatonin. J Pineal Res 25:184–191.
   PubMed Web of Science ®Google Scholar
• Tan DX, Manchester LC, Reiter RJ, Qi W, Hanes MA and Farley NJ. 1999a. High physiological levels of melatonin in the bile of mammals. Life Sci 65:2523–2529.
   Google Scholar
• Tan DX, Manchester LC, Reiter RJ, Qi W, Zhang M, Weintraub ST, Cabrera J, Sainz RM and Mayo JC. 1999b. Identification of highly elevated levels of melatonin in bone marrow: its origin and significance. Biochem Biophys Acta 1472:206–214.
   PubMed Web of Science ®Google Scholar
• Tan DX, Manchester CC, Reiter RJ, Plummer BF, Limson J, Weintraub ST and Qi W. 2000. Melatonin directly scavenges hydrogen peroxide: a potentially new metabolic pathway of melatonin biotransformation. Free Radic Biol Med 29:177–1185.
   Google Scholar
• Tan DX, Reiter RJ, Manchester LC, Yan MT, El-Sawi M, Sainz RM, Mayo JC, Cohen R, Allegra M and Hardeland R. 2002. Chemical and physical properties and potential mechanisms: melatonin as a broad spectrum antioxidant and free radical scavenger. Curr Top Med Chem 2:181–197.
   PubMedGoogle Scholar
• Tan DX, Hardeland R, Manchester LC, Poeggeler B, Lopez-Burillo S, Mayo JC, Sainz RM and Reiter RJ. 2003. Mechanistic and comparative studies of melatonin and classic antioxidants in terms of their interactions with ABTS cation radical. J Pineal Res 34:249–259.
   PubMed Web of Science ®Google Scholar
• Tan DX, Manchester LC, Terron MP, Flores LJ and Reiter RJ. 2007a. One molecule, many derivatives: a never-ending interaction of melatonin with reactive oxygen and nitrogen species. J Pineal Res 42:28–42.
   PubMed Web of Science ®Google Scholar
• Tan DX, Manchester LC, Di Mascio P, Martinez GR, Prado FM and Reiter RJ. 2007b. Novel rhythms of N1-acetyl-N2-formyl-5-methoxykynuramine and its precursor melatonin in water hyacinth: importance in phytoremediation. FASEB J 21:1724–1729.
   PubMed Web of Science ®Google Scholar
• Tan DX, Manchester LC, Helton P and Reiter RJ. 2007c. Phytoremediative capacity of plants enriched with melatonin. Plant Sign Behav 2:514–516.
   PubMedGoogle Scholar
• Tengattini S, Reiter RJ, Tan DX, Terron MP, Rodella LF and Rezzani R. 2008. Cardiovascular disease: protective effects of melatonin. J Pineal Res 44:16–25.
   PubMed Web of Science ®Google Scholar
• Tesoriere L, Avellone G, Ceraulo L, D’Arpa D, Allegra M and Livrea MA. 2001. Oxidation of melatonin by oxoferryl hemoglobin: a mechanistic study. Free Radic Res 35:633–642.
   PubMed Web of Science ®Google Scholar
• Than NN, Heer C, Laatsch H and Hardeland R. 2006. Reactions of the melatonin metabolite, N1-acetyl-5-methoxykynuramine (AMK) with the ABTS cation radical: identification of new oxidation products. Redox Rep 11:15–24.
   PubMed Web of Science ®Google Scholar
• Thieblot L and Le Bars H. 1955. Le Glande Pineole an Epiphyes. Paris: Maloine.
   Google Scholar
• Tilden AR, Becker MA, Amma LL, Arcinceger J and McGaw AK. 1997. Melatonin production in an aerobic photosynthetic bacterium: an evolutionary early association with darkness. J Pineal Res 22:102–106.
   Google Scholar
• Tomas-Zapico C and Coto-Montes A. 2005. A proposed mechanism to explain the stimulatory effect of melatonin on antioxidative enzymes. J Pineal Res 39:99–104.
   PubMed Web of Science ®Google Scholar
• Topal T, Oztas Y, Korkmaz A, Sadir S, Oter S, Coskun O and Bilgic H. 2005. Melatonin ameliorates bladder damage induced by cyclophosphamide in rats. J Pineal Res 38:272–277.
   PubMed Web of Science ®Google Scholar
• Troiani ME, Reiter RJ, Vaughan MK, Oakin S and Vaughan GM. 1988a. Swimming depresses nighttime melatonin content without changing N-acetyltransferase activity in the rat pineal gland. Neuroendocrinology 47:55–60.
   PubMed Web of Science ®Google Scholar
• Troiani ME, Reiter RJ, Tannenbaum MG, Puig-Domingo M, Guerrero JM and Menendez-Pelaez A. 1988b. Neither the pituitary nor the sympathetic nervous system is responsible for eliciting the large drop in elevated rat pineal melatonin levels due to swimming. J Neurol Transm 74:14–460.
   Google Scholar
• Tunez I, Munoz MC, Medina FJ, Salcedo M, Feijoo M and Montilla P. 2007. Comparison of melatonin, vitamin E and L-carnitine in the treatment of neuro- and hepatotoxicity induced by thioacetamide. Cell Biochem Funct 25:119–127.
   PubMedGoogle Scholar
• Turjanski AG, Rosenstein RE and Estrin DA. 1998. Reactions of melatonin and related indoles with free radicals: a computational study. J Med Chem 41:3684–3689.
   PubMed Web of Science ®Google Scholar
• Turjanski AG, Saenz DA, Doctorovich F, Estrin DA and Rosenstein RE. 2001. Nitrosation of melatonin by nitric oxide: a computational study. J Pineal Res 33:31–36.
   Google Scholar
• Urata Y, Honma S, Goto S, Todoroki S, Iida T, Cho S, Honma K and Kondo T. 1999. Melatonin induces gamma-glutamyl cysteine synthase mediated by activator protein-1 in human vascular endothelial cells. Free Rad Biol Med 27:838–847.
   PubMed Web of Science ®Google Scholar
• Valeyrie-Allanore I, Poulalhon W, Fagot JP, Sekula P, Anidovici B, Sidorff A, Mockenhaupt M. 2008. Stevens-Johnson syndrome and toxic experimental necrolysis induced by amifostine during head and neck radiotherapy. Radiother Oncol 87:300–303.
   PubMedGoogle Scholar
• Velkov ZA, Velkov YZh, Galunska BT, Paskalev DN and Todjer AV. 2009. Melatonin: quantum-chemical and biochemical investigation of antioxidant activity. Eur J Med Chem, 44: 2834–2839.
   Google Scholar
• Vijayalaxmi, Reiter RJ and Meltz ML. 1995a. Melatonin protects human blood lymphocytes from radiation induced chromosome damage. Mutat Res 346:23–31.
   PubMed Web of Science ®Google Scholar
• Vijayalaxmi, Reiter RJ, Sewerynek E, Poeggeler B, Leal BZ and Meltz JL. 1995b. Marked reduction in radiation-induced micronuclei in human blood lymphocytes pretreated with melatonin. Radiat Res 43:102–106.
   Google Scholar
• Vijayalaxmi, Reiter RJ, Leal BZ and Meltz ML. 1996a. Effect of melatonin on mitotic and proliferative indices, and sister chromatid exchange in human blood lymphocytes. Mutat Res 351:187–192.
   PubMed Web of Science ®Google Scholar
• Vijayalaxmi, Reiter RJ and Meltz ML. 1996b. Melatonin and radioprotection from genetic damage: in vivo/in vitro studies with human volunteers. Mutat Res 371 221–228.
   PubMed Web of Science ®Google Scholar
• Vijayalaxmi, Reiter RJ, Herman TS and Meltz ML. 1996c. Melatonin and radioprotection from genetic damage: in vivo/in vitro studies with cells from human volunteers. Mutat Res 371:221–228.
   PubMed Web of Science ®Google Scholar
• Vijayalaxmi, Meltz ML, Reiter RJ and Herman TS. 1999a. Melatonin and protection from genetic damage in blood and bone marrow: whole body radiation studies in mice. J Pineal Res 27:221–225.
   PubMed Web of Science ®Google Scholar
• Vijayalaxmi, Meltz ML, Reiter RJ, Herman TS and Kumar S. 1999b. Melatonin and protection from whole body radiation: survival studies in mice. Mutat Res 425:21–27.
   PubMed Web of Science ®Google Scholar
• Vijayalaxmi, Meltz ML, Reiter RJ and Herman TS. 1999c. Melatonin and protection from genetic damage in blood and bone marrow: whole-body irradiation studies in mice. J Pineal Res 27:221–225.
   PubMed Web of Science ®Google Scholar
• Vijayalaxmi, Reiter RJ, Tan DX, Herman TS and Thomas Jr CR. 2004. Melatonin as a radioprotective agent: a review. Int J Radiat Oncol Biol Phys 59:639–653.
   PubMed Web of Science ®Google Scholar
• Vivien-Roels B and Pevet P. 1993. Melatonin, presence and formation in invertebrates. Experientia 49:642–647.
   Google Scholar
• Wakatsuki A, Okatani Y, Shinohara K, Ikenoue N and Fukaya T. 2001. Melatonin protects against ischemia/reperfusion induced oxidative damage to mitochondria in fetal rat brain. J Pineal Res 31:167–172.
   PubMed Web of Science ®Google Scholar
• Weaver DR. 1997. Reproductive safety of melatonin: a “wonder drug” to wonder about. J Biol Rhythms 12:682–689.
   PubMed Web of Science ®Google Scholar
• Weisenberg I, Missbach M, Kahlen JP, Schrader M and Carlberg C. 1995. Transcriptional activation of the nuclear receptor RZR alpha by the pineal gland hormone melatonin and identification CGP 52608 as a synthetic ligand. Nucleic Acids Res 23:327–333.
   Google Scholar
• Weishaupt JH, Bartels C, Polking E, Dietrich J, Rhode G, Poeggeler B, Mertens N, Sperling S, Bohn M, Huether G, Schneider A, Bach A, Siren AL, Hardeland R, Bahr M, Navek A, and Ehrenreich H. 2006. Reduced oxidative damage in ALS by high-dose enteral melatonin treatment. J Pineal Res 41:313–323.
   PubMed Web of Science ®Google Scholar
• Welin AK, Svedin P, La Patto R, Sultan R, Hagberg H, Gressens P, Kjellmer I and Mallard C. 2007. Melatonin reduces inflammation and cell death in white matter in the midgestation fetal sheep following umbilical cord occlusion. Pediatr Res 61:153–158.
   PubMed Web of Science ®Google Scholar
• Whiteman M, Dogra Y, Winyard PG and Armstrong JS. 2008. Detection and measurement of reactive oxygen intermediates in mitochondria and cells. Meth Mol Biol 476:29–50.
   Google Scholar
• Winiarska K, Fraczyk T, Malinska D, Drozak J and Bryla J. 2006. Melatonin attenuates diabetes-induced oxidative stress in rabbits. J Pineal Res 40:168–176.
   PubMed Web of Science ®Google Scholar
• Winston GW, Regoli F, Dugas Jr AJ, Fong JH and Blanchard KA. 1998. A rapid gas chromatographic assay for determining oxyradical scavenging activity of antioxidants and biological fluids. Free Radic Biol Med 24:480–493.
   PubMed Web of Science ®Google Scholar
• Wolfler A, Caluba HC, Abuja PM, Pohr G, Schauenstein K and Liebmann PM. 2001. Prooxidant activity of melatonin promotes fas-induced cell death in human leukemic Jurkat cells. FEBS Lett 502:127–131.
   PubMed Web of Science ®Google Scholar
• Wu WT, Reiter RJ, Troiani ME and Vaughan GM. 1987. Elevated daytime rat pineal and serum melatonin levels induced by isoproterenol are depressed by swimming. Life Sci 41:1473–1479.
   PubMed Web of Science ®Google Scholar
• Wu WT, Chen YC and Reiter RJ. 1988. Day-night differences in the response of the pineal gland to swimming stress. Proc Soc Exp Biol Med 187:315–319.
   Google Scholar
• Ximenes VF, Catalini LH and Campa IH. 2001. Oxidation of melatonin and tryptophan by an HRP cycle involving compound III. Biochem. Biophys Res Commun 287:130–134.
   PubMed Web of Science ®Google Scholar
• Yilmaz S and Yilmaz E. 2006. Effects of melatonin and vitamin E in oxidative-antioxidative status in rats exposed to irradiation. Toxicology 222:1–7.
   PubMed Web of Science ®Google Scholar
• Yilmaz T, Celebi S and Kukner AS. 2002. The protective effects of melatonin, vitamin E and octreotide on retinal edema during ischemia-reperfusion in the guinea pig. Eur J Ophthalmol 12:443–449.
   PubMed Web of Science ®Google Scholar
• Yin J, Liu YH, Xu YF, Zhang YJ, Chen JG, Shu BH and Wang JZ. 2006. Melatonin arrests peroxynitrite-induced tau hyperphosphorylation and the over activation of protein kinases in rat brain. J Pineal Res 42:124–129.
   Google Scholar
• Zavodnik IB, Domanski AV, Lapshina EA, Bryzewska M and Reiter RJ. 2006. Melatonin directly scavenges free radicals generated in red blood cells and a cell-free system: chemiluminescence measurements and theoretical calculations. Life Sci 79:391–400.
   PubMed Web of Science ®Google Scholar
• Zhang H, Squadrito GL and Pryor WA. 1998. The reaction of melatonin with peroxynitrite: formation of melatonin radical cation and absence of stable nitrated products. Biochem Biophys Res Commun 251:83–87.
   PubMedGoogle Scholar
• Zhang H, Squadrito GL, Uppu R and Pryor WA. 1999. Reaction of peroxynitrite with melatonin: a mechanistic study. Chem Res Toxicol 12:526–534.
   PubMed Web of Science ®Google Scholar
• Zupancic D, Jezernik K and Vidmar G. 2008. Effect of melatonin apoptosis, proliferation and differentiation of urothelial cells after cyclophosphamide treatment. J Pineal Res 44:299–306.
   PubMed Web of Science ®Google Scholar