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Melatonin: The Antioxidant Power Of Darkness

Year 2004, Volume: 13 Issue: 2, 56 - 66, 01.09.2004

Abstract

Oxidative stress in biological systems resulting from the overproduction of free radicals is implicated in the pathogenesis of many diseases. The organism defends itself by agents called antioxidants against oxidative damage by free radicals, which show prooxidant activity. Melatonin (MEL), the chief secretory product of the pineal gland, has been shown to have in vivo and in vitro antioxidant effects other than endocrine and biological functions. Moreover, MEL is considered the most powerful antioxidant (among the others), therefore there is growing interest to MEL and also evidence showing the importance of its antioxidant action. In the present review, the antioxidative properties of MEL along with its synthesis and biological effects as well as its clinical importance are described

References

  • Sies H. Oxidative stress: Oxidants and antioxidants. Exp Physiol 1997, 82: 291-295. 2. Dalle-Donne I, Rossi R, Giustarini D, Milzani A, Colombo R. Protein carbonyl groups as biomarkers of oxidative stress. Clin Chim Acta 2003, 329: 23-38. 3. Halliwell B, Gutteridge JMC. Free radicals in biology and medicine 2nd ed. Clarendon Press, Oxford 1996, pp 10-19, 86-130.
  • Valentine JS, Wertz DL, Lyons TJ, et al. The dark side of dioxygen biochemistry. Curr Opin Chem Biol 1998, 2: 253-262. 5. Witko-Sarsat V, Rieu P, Descamps-Latscha B, Lesavre P, Mecarelli LH. Neutrophils: Molecules, functions and pathophysiological aspects. Lab Invest 2000, 80: 617-635.
  • Halliwell B. Drug antioxidant effects. A basis for drug selection? Drugs 1991, 42: 569-605.
  • Brzezinski A. Melatonin in humans. N Engl J Med 1997, 336: 186-195.
  • Lerner AB, Case JD, Takahashi Y, Lee TH, Mori W. Isolation of melatonin, the pineal gland factor that lightens melanocytes. J Am Chem Soc 1958, 80: 2587.
  • Reiter RJ. Interactions of the pineal hormone melatonin with oxygen-centered free radicals: a brief review. Brazilian J Med Biol Res 1993, 26: 1141-1155.
  • Arendt J. Melatonin. Clin Endocrinol 1988, 29: 205-229.
  • Reiter RJ. Pineal melatonin: Cell biology of its synthesis and of its physiological interactions. Endocr Rev 1991, 12 : 151-180.
  • Sugden D. Melatonin biosynthesis in the mammalian pineal gland. Experientia 1989, 45: 922-932.
  • Poeggeler B, Reiter RJ, Tan D-X, Chen L-D, Manchester LC. Melatonin, hydroxyl radical mediated oxidative damage, and aging: A hypothesis. J Pineal Res 1993, 14: 151-168.
  • Acuna CD, Reiter RJ, Menendez PA, Pablos MI, Burgos A. Characterization of high-affinity melatonin binding sites in purified cell nuclei of rat liver. J Pineal Res 1994, 16: 100-112.
  • Forsling ML. Melatonin. Curr Opin Endocrinol Diabetes 2001, 8: l47-l53.
  • Hardeland R, Reiter RJ, Poeggeler B, Tan D-X. The significance of the metabolism of the neurohormone melatonin: Antioxidative protection and formation of bioactive substances. Neurosci Biobehav Rev 1993, 17: 347-357.
  • Ianas O, Olivescu R, Badescu I. Melatonin involvement in oxidative processes. Rom J Endocrinol 1991, 29:117-123.
  • Tan D-X, Chen L-D, Poeggeler B, Manchester LC, Reiter RJ. Melatonin: a potent endogenous hydroxyl radical scavenger. Endocr J 1993, 1: 57-60.
  • Pahkla R, Zilmer M, Kullisaar T, Rago L. Comparison of the antioxidant activity of melatonin and pinoline in vitro. J Pineal Res 1998, 24: 96-101.
  • Giusti P, Lipartiti M, Franceschini D, Schiavo N, Floreani M, Manev H. Neuroprotection by melatonin from kainate-induced excitotoxicity in rats. FASEB J 1996, 10: 891-896.
  • Sewerynek E, Reiter RJ, Melchiorri D, Ortiz GG, Lewinski A. Oxidative damage in the liver induced by ischemia reperfusion: Protection by melatonin. Hepatogastroenterology 1996, 43: 898-905.
  • Pierrefiche G, Topall G, Courboin G, Henriet I, Laborit H. Antioxidant activity of melatonin in mice. Res Commun Chem Pathol Pharmacol 1993, 80: 211-223.
  • Yamamoto HA, Tang HW. Melatonin attenuates L-cysteine induced seizures and lipid peroxidation in the brain of mice. J Pineal Res 1996, 21: 108-113.
  • Beyer CE, Steketee JD, Saphier D. Antioxidant properties of melatonin-an emerging mystery. Biochem Pharmacol 1998, 56: 1265-1272.
  • Reiter RJ, Tan DX, Osuna C, Gitto E. Actions of melatonin in the reduction of oxidative stress. J Biomed Sci 2000, 7: 444- 458.
  • Kotler M, Rodriguez C, Sainz RM, Antolin I, Menendez-Pelaez A. Melatonin increases gene expression for antioxidant enzymes in rat brain cortex. J Pineal Res 1998, 24: 83- 89.
  • Thomas L, Drew JE, Abramovich DR, Williams LM. The role of melatonin in the human fetus (review). Int J Mol Med. 1998, 1:539-543.
  • Reiter RJ. Functional aspects of the pineal hormone melatonin in combating cell and tissue damage induced by free radicals. Eur J Endocrinol 1996, 134: 412-420.
  • Pablos MI, Reiter RJ, Ortiz GG, et al. Rhythms of glutathione peroxidase and glutathione reductase in brain of chick and their inhibition by light. Neurochem Int 1998, 32: 69-75.
  • Yazıcı C. Sentetik Seks Steroidlerinin ve Melatoninin Oksidan Antioksidan Sistem Üzerine Etkilerinin Rat Modelinde Araştırılması. Uzmanlık Tezi, Erciyes Ün. Tıp Fakültesi Biyokimya A.D, Kayseri 1999, 151.
  • Urata Y, Honma S, Goto S, et al. Melatonin induces gamma-glutamylcysteine synthetase mediated by activator protein-1 in human vascular endothelial cells. Free Radic Biol Med. 1999, 27:838-847
  • Bettahi I, Guerrero JM, Reiter RJ, Osuna C. Physiological concentrations of melatonin inhibit the norepinephrine-induced activation of prostaglandin E2 and cyclic AMP production in rat hypothalamus: a mechanism involving inhibiton of nitric oxide synthase. J Pineal Res. 1998, 25:34-40.
  • Guerrero JM, Reiter RJ, Ortiz GG, Pablos MI, Sewerynek E, Chuang JI. Melatonin prevents increases in neural nitric oxide and cyclic GMP production after transient brain ischemia and reperfusion in the Mongolian gerbil (Meriones unguiculatus). J Pineal Res. 1997, 23:24-31.
  • Hara M, Yoshida M, Nishijima H, et al. Melatonin, a pineal secretory product with antioxidant properties, protects against cisplatin-induced nephrotoxicity in rats. J Pineal Res 2001, 30: 129-138.
  • Montilla P, Tunez I, Munoz MC, Lopez A, Soria JV. Hyperlipemic nephropathy induced by adriamycin: Effect of melatonin administration. Nephron 1997, 76: 345-350.
  • Montilla PL, Vargas JF, Tunez IF, Munoz de Agueda MC, Valdelvira ME, Cabrera ES. Oxidative stress in diabetic rats induced by streptozotocin: protective effects of melatonin. J Pineal Res 1998, 25: 94-100.
  • Köse K, Yazıcı C. The effect of levonorgestrel and melatonin treatments on plasma oxidant- antioxidant system, and lipid/lipoprotein levels in female rats. Turk J Med Sci 2000, 30:523-528.
  • Köse K, Yazıcı C. Ratlara uygulanan levonorgestrel ve melatoninin hepatik glutatyon ve malondialdehit seviyelerine etkisi. Erciyes Tıp Dergisi 2001, 23:1-6.
  • Köse K, Yazıcı C. Ratlarda, levonorgestrel ve melatonin uygulamasının plazma lipid, lipoprotein, malondialdehit, konjuge dien ve tiyol seviyelerine etkisi. Klinik Biyokimya Derneği Ateroskleroz Sempozyumu Özet Kitabı, İzmir 19-20 Mart 1999, B-47.
  • Köse K, Yazıcı C. Levonorgestrel ve melatonin uygulamasının rat karaciğer glutatyon redoks siklusu üzerine etkisi. XVIII. Gevher Nesibe Tıp Günleri, III. Deneysel ve Klinik Araştırma Kongresi ve "Workshop"'u Özet Kitabı, Kayseri 18-20 Mayıs 2000, P 28.
  • Yazıcı C, Köse K, Gökalp S, Canöz Ö, Utaş C. Siklosporin A nefrotoksisitesinde protein oksidasyonunun yeri ve melatoninin koruyucu etkisi. 19. TND Ulusal Nefroloji Hipertansiyon Diyaliz ve Transplantasyon Kongresi Nefroloji Diyaliz ve Transplantasyon Dergisi Bildiri Özet Kitabı, Antalya 17-21 Eylül 2002, P-119.
  • Deveci S, Yazıcı C, Köse K, Gökalp S.S. Siklosporin A ve/veya melatonin uygulanan ratlarda kanser riskini artıran oksidatif stresin değerlendirilmesi. Klinik Biyokimya ve Kanser Sempozyumu Özet Kitabı, Bursa 26-29 Eylül 2002, P-21.
  • Reiter RJ. Melatonin: clinical relevance. Best Pract Res Clin Endocrinol Metab. 2003, 17:273-285.
  • Brusco LI, Marquez M & Cardinali DP. Monozygotic twins in Alzheimer’s disease treated with melatonin: case report. J Pineal Res 1998, 25: 260–263.
  • Gitto E, Karbownik M, Reiter RJ et al. Effects of melatonin treatment in septic newborns. Pediatr Res 2001, 50: 756–760.
  • Fulia F, Gitto E, Cuzzocrea S et al. Increased levels of malondialdehyde and nitrite/nitrate in the blood of asphyxiated newborns:

MELATONİN: KARANLIĞIN ANTİOKSİDAN GÜCÜ

Year 2004, Volume: 13 Issue: 2, 56 - 66, 01.09.2004

Abstract

Biyolojik sistemlerde prooksidan/antioksidan dengenin bozulmasıyla oluşan oksidatif stres, birçok patolojik durumla ilişkilendirilmektedir. Organizma, prooksidan etki gösteren serbest radikallerin hasarına karşı, antioksidan adı verilen ajanlarla kendini savunur. Pineal bezin başlıca salgısı olan melatoninin (MEL) endokrin ve sirkadiyen ritm üzerine bilinen etkilerinden başka, in vivo ve in vitro antioksidan etkiye de sahip olduğu gösterilmiştir. Hatta, antioksidanlar içerisinde, MEL’in en güçlü radikal tutucu olduğu öne sürüldüğünden, MEL’e olan ilgi giderek artmakta ve antioksidan özelliği gün geçtikçe önem kazanmaktadır. Bu derlemede MEL’in sentezi ve biyolojik etkilerinin yanı sıra antioksidan özellikleri ile ilgili çalışmalar değerlendirilerek klinik önemi tartışılmıştır

References

  • Sies H. Oxidative stress: Oxidants and antioxidants. Exp Physiol 1997, 82: 291-295. 2. Dalle-Donne I, Rossi R, Giustarini D, Milzani A, Colombo R. Protein carbonyl groups as biomarkers of oxidative stress. Clin Chim Acta 2003, 329: 23-38. 3. Halliwell B, Gutteridge JMC. Free radicals in biology and medicine 2nd ed. Clarendon Press, Oxford 1996, pp 10-19, 86-130.
  • Valentine JS, Wertz DL, Lyons TJ, et al. The dark side of dioxygen biochemistry. Curr Opin Chem Biol 1998, 2: 253-262. 5. Witko-Sarsat V, Rieu P, Descamps-Latscha B, Lesavre P, Mecarelli LH. Neutrophils: Molecules, functions and pathophysiological aspects. Lab Invest 2000, 80: 617-635.
  • Halliwell B. Drug antioxidant effects. A basis for drug selection? Drugs 1991, 42: 569-605.
  • Brzezinski A. Melatonin in humans. N Engl J Med 1997, 336: 186-195.
  • Lerner AB, Case JD, Takahashi Y, Lee TH, Mori W. Isolation of melatonin, the pineal gland factor that lightens melanocytes. J Am Chem Soc 1958, 80: 2587.
  • Reiter RJ. Interactions of the pineal hormone melatonin with oxygen-centered free radicals: a brief review. Brazilian J Med Biol Res 1993, 26: 1141-1155.
  • Arendt J. Melatonin. Clin Endocrinol 1988, 29: 205-229.
  • Reiter RJ. Pineal melatonin: Cell biology of its synthesis and of its physiological interactions. Endocr Rev 1991, 12 : 151-180.
  • Sugden D. Melatonin biosynthesis in the mammalian pineal gland. Experientia 1989, 45: 922-932.
  • Poeggeler B, Reiter RJ, Tan D-X, Chen L-D, Manchester LC. Melatonin, hydroxyl radical mediated oxidative damage, and aging: A hypothesis. J Pineal Res 1993, 14: 151-168.
  • Acuna CD, Reiter RJ, Menendez PA, Pablos MI, Burgos A. Characterization of high-affinity melatonin binding sites in purified cell nuclei of rat liver. J Pineal Res 1994, 16: 100-112.
  • Forsling ML. Melatonin. Curr Opin Endocrinol Diabetes 2001, 8: l47-l53.
  • Hardeland R, Reiter RJ, Poeggeler B, Tan D-X. The significance of the metabolism of the neurohormone melatonin: Antioxidative protection and formation of bioactive substances. Neurosci Biobehav Rev 1993, 17: 347-357.
  • Ianas O, Olivescu R, Badescu I. Melatonin involvement in oxidative processes. Rom J Endocrinol 1991, 29:117-123.
  • Tan D-X, Chen L-D, Poeggeler B, Manchester LC, Reiter RJ. Melatonin: a potent endogenous hydroxyl radical scavenger. Endocr J 1993, 1: 57-60.
  • Pahkla R, Zilmer M, Kullisaar T, Rago L. Comparison of the antioxidant activity of melatonin and pinoline in vitro. J Pineal Res 1998, 24: 96-101.
  • Giusti P, Lipartiti M, Franceschini D, Schiavo N, Floreani M, Manev H. Neuroprotection by melatonin from kainate-induced excitotoxicity in rats. FASEB J 1996, 10: 891-896.
  • Sewerynek E, Reiter RJ, Melchiorri D, Ortiz GG, Lewinski A. Oxidative damage in the liver induced by ischemia reperfusion: Protection by melatonin. Hepatogastroenterology 1996, 43: 898-905.
  • Pierrefiche G, Topall G, Courboin G, Henriet I, Laborit H. Antioxidant activity of melatonin in mice. Res Commun Chem Pathol Pharmacol 1993, 80: 211-223.
  • Yamamoto HA, Tang HW. Melatonin attenuates L-cysteine induced seizures and lipid peroxidation in the brain of mice. J Pineal Res 1996, 21: 108-113.
  • Beyer CE, Steketee JD, Saphier D. Antioxidant properties of melatonin-an emerging mystery. Biochem Pharmacol 1998, 56: 1265-1272.
  • Reiter RJ, Tan DX, Osuna C, Gitto E. Actions of melatonin in the reduction of oxidative stress. J Biomed Sci 2000, 7: 444- 458.
  • Kotler M, Rodriguez C, Sainz RM, Antolin I, Menendez-Pelaez A. Melatonin increases gene expression for antioxidant enzymes in rat brain cortex. J Pineal Res 1998, 24: 83- 89.
  • Thomas L, Drew JE, Abramovich DR, Williams LM. The role of melatonin in the human fetus (review). Int J Mol Med. 1998, 1:539-543.
  • Reiter RJ. Functional aspects of the pineal hormone melatonin in combating cell and tissue damage induced by free radicals. Eur J Endocrinol 1996, 134: 412-420.
  • Pablos MI, Reiter RJ, Ortiz GG, et al. Rhythms of glutathione peroxidase and glutathione reductase in brain of chick and their inhibition by light. Neurochem Int 1998, 32: 69-75.
  • Yazıcı C. Sentetik Seks Steroidlerinin ve Melatoninin Oksidan Antioksidan Sistem Üzerine Etkilerinin Rat Modelinde Araştırılması. Uzmanlık Tezi, Erciyes Ün. Tıp Fakültesi Biyokimya A.D, Kayseri 1999, 151.
  • Urata Y, Honma S, Goto S, et al. Melatonin induces gamma-glutamylcysteine synthetase mediated by activator protein-1 in human vascular endothelial cells. Free Radic Biol Med. 1999, 27:838-847
  • Bettahi I, Guerrero JM, Reiter RJ, Osuna C. Physiological concentrations of melatonin inhibit the norepinephrine-induced activation of prostaglandin E2 and cyclic AMP production in rat hypothalamus: a mechanism involving inhibiton of nitric oxide synthase. J Pineal Res. 1998, 25:34-40.
  • Guerrero JM, Reiter RJ, Ortiz GG, Pablos MI, Sewerynek E, Chuang JI. Melatonin prevents increases in neural nitric oxide and cyclic GMP production after transient brain ischemia and reperfusion in the Mongolian gerbil (Meriones unguiculatus). J Pineal Res. 1997, 23:24-31.
  • Hara M, Yoshida M, Nishijima H, et al. Melatonin, a pineal secretory product with antioxidant properties, protects against cisplatin-induced nephrotoxicity in rats. J Pineal Res 2001, 30: 129-138.
  • Montilla P, Tunez I, Munoz MC, Lopez A, Soria JV. Hyperlipemic nephropathy induced by adriamycin: Effect of melatonin administration. Nephron 1997, 76: 345-350.
  • Montilla PL, Vargas JF, Tunez IF, Munoz de Agueda MC, Valdelvira ME, Cabrera ES. Oxidative stress in diabetic rats induced by streptozotocin: protective effects of melatonin. J Pineal Res 1998, 25: 94-100.
  • Köse K, Yazıcı C. The effect of levonorgestrel and melatonin treatments on plasma oxidant- antioxidant system, and lipid/lipoprotein levels in female rats. Turk J Med Sci 2000, 30:523-528.
  • Köse K, Yazıcı C. Ratlara uygulanan levonorgestrel ve melatoninin hepatik glutatyon ve malondialdehit seviyelerine etkisi. Erciyes Tıp Dergisi 2001, 23:1-6.
  • Köse K, Yazıcı C. Ratlarda, levonorgestrel ve melatonin uygulamasının plazma lipid, lipoprotein, malondialdehit, konjuge dien ve tiyol seviyelerine etkisi. Klinik Biyokimya Derneği Ateroskleroz Sempozyumu Özet Kitabı, İzmir 19-20 Mart 1999, B-47.
  • Köse K, Yazıcı C. Levonorgestrel ve melatonin uygulamasının rat karaciğer glutatyon redoks siklusu üzerine etkisi. XVIII. Gevher Nesibe Tıp Günleri, III. Deneysel ve Klinik Araştırma Kongresi ve "Workshop"'u Özet Kitabı, Kayseri 18-20 Mayıs 2000, P 28.
  • Yazıcı C, Köse K, Gökalp S, Canöz Ö, Utaş C. Siklosporin A nefrotoksisitesinde protein oksidasyonunun yeri ve melatoninin koruyucu etkisi. 19. TND Ulusal Nefroloji Hipertansiyon Diyaliz ve Transplantasyon Kongresi Nefroloji Diyaliz ve Transplantasyon Dergisi Bildiri Özet Kitabı, Antalya 17-21 Eylül 2002, P-119.
  • Deveci S, Yazıcı C, Köse K, Gökalp S.S. Siklosporin A ve/veya melatonin uygulanan ratlarda kanser riskini artıran oksidatif stresin değerlendirilmesi. Klinik Biyokimya ve Kanser Sempozyumu Özet Kitabı, Bursa 26-29 Eylül 2002, P-21.
  • Reiter RJ. Melatonin: clinical relevance. Best Pract Res Clin Endocrinol Metab. 2003, 17:273-285.
  • Brusco LI, Marquez M & Cardinali DP. Monozygotic twins in Alzheimer’s disease treated with melatonin: case report. J Pineal Res 1998, 25: 260–263.
  • Gitto E, Karbownik M, Reiter RJ et al. Effects of melatonin treatment in septic newborns. Pediatr Res 2001, 50: 756–760.
  • Fulia F, Gitto E, Cuzzocrea S et al. Increased levels of malondialdehyde and nitrite/nitrate in the blood of asphyxiated newborns:
There are 43 citations in total.

Details

Other ID JA54TG62ZH
Journal Section Research Article
Authors

Cevat Yazıcı This is me

Kader Köse This is me

Publication Date September 1, 2004
Submission Date September 1, 2004
Published in Issue Year 2004 Volume: 13 Issue: 2

Cite

APA Yazıcı, C., & Köse, K. (2004). MELATONİN: KARANLIĞIN ANTİOKSİDAN GÜCÜ. Sağlık Bilimleri Dergisi, 13(2), 56-66.
AMA Yazıcı C, Köse K. MELATONİN: KARANLIĞIN ANTİOKSİDAN GÜCÜ. JHS. September 2004;13(2):56-66.
Chicago Yazıcı, Cevat, and Kader Köse. “MELATONİN: KARANLIĞIN ANTİOKSİDAN GÜCÜ”. Sağlık Bilimleri Dergisi 13, no. 2 (September 2004): 56-66.
EndNote Yazıcı C, Köse K (September 1, 2004) MELATONİN: KARANLIĞIN ANTİOKSİDAN GÜCÜ. Sağlık Bilimleri Dergisi 13 2 56–66.
IEEE C. Yazıcı and K. Köse, “MELATONİN: KARANLIĞIN ANTİOKSİDAN GÜCÜ”, JHS, vol. 13, no. 2, pp. 56–66, 2004.
ISNAD Yazıcı, Cevat - Köse, Kader. “MELATONİN: KARANLIĞIN ANTİOKSİDAN GÜCÜ”. Sağlık Bilimleri Dergisi 13/2 (September 2004), 56-66.
JAMA Yazıcı C, Köse K. MELATONİN: KARANLIĞIN ANTİOKSİDAN GÜCÜ. JHS. 2004;13:56–66.
MLA Yazıcı, Cevat and Kader Köse. “MELATONİN: KARANLIĞIN ANTİOKSİDAN GÜCÜ”. Sağlık Bilimleri Dergisi, vol. 13, no. 2, 2004, pp. 56-66.
Vancouver Yazıcı C, Köse K. MELATONİN: KARANLIĞIN ANTİOKSİDAN GÜCÜ. JHS. 2004;13(2):56-6.