Toxicity of non-steroidal anti-inflammatory drugs: A review of melatonin and diclofenac sodium association

Histology and Histopathology

Volumn 27, Issue 4, 2012, Pages 417-436

  Aygün, Dursun ^a   Kaplan, Süleyman ^a   Odaci, Ersan ^b   Onger, Mehmet E ^a   Altunkaynak, M Eyüp ^a  

^a ONDOKUZ MAYIS UNIVERSITY SCHOOL OF MEDICINE   (Turkey)

^b KARADENIZ TECHNICAL UNIVERSITY   (Turkey)

Author keywords

Diclofenac sodium; Melatonin; Neuroprotective effect; Nonsteroidal anti inflammatory drug

Indexed keywords

DICLOFENAC; FREE RADICAL; MELATONIN; NEUROPROTECTIVE AGENT; NONSTEROID ANTIINFLAMMATORY AGENT; SCAVENGER;

ANIMAL; APOPTOSIS; BIOSYNTHESIS; BRAIN; DRUG ANTAGONISM; DRUG EFFECT; HUMAN; METABOLISM; OXIDATIVE STRESS; PATHOLOGY; REVIEW;

ANIMALS; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; APOPTOSIS; BRAIN; DICLOFENAC; DRUG ANTAGONISM; FREE RADICAL SCAVENGERS; FREE RADICALS; HUMANS; MELATONIN; NEUROPROTECTIVE AGENTS; OXIDATIVE STRESS;

EID: 84857711981     PISSN: 02133911     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (223)

1. Abe M., Reiter R.J., Orhii P.B., Hara M. and Poeggeler B. (1994). Inhibitory effect of melatonin on cataract formation in newborn rats: evidence for an antioxidative role for melatonin. J. Pineal Res. 17, 94-100.
2. Acuña-Castroviejo D., Martín M., Macías M., Escames G., León J., Khaldy H. and Reiter R. J. (2001). Melatonin, mitochondria, and cellular bioenergetics. J. Pineal Res. 30, 65-74.
3. Acuña-Castroviejo D., Escames G., León J., Carazo A., and Khaldy H. (2003). Mitochondrial regulation by melatonin and its metabolites. Adv. Exp. Med. Biol. 527, 549-557.
4. Agarwal A. and Prabakaran S.A. (2005). Mechanism, measurement, and prevention of oxidative stress in male reproductive physiology. Indian J. Exp. Biol. 43, 963-974.
5. Akbulut K.G., Gönül B. and Akbulut H. (1999). Differential effects of pharmacological doses of melatonin on malondialdehyde and glutathione levels in young and old rats. Gerontology 45, 67-71.
6. Akbulut K.G., Gonül B. and Akbulut H. (2008). Exogenous melatonin decreases age-induced lipid peroxidation in the brain. Brain Res. 1238, 31-35.
7. Allegra M., Reiter R.J., Tan D.X., Gentile C., Tesoriere L. and Livrea M.A. (2003). The chemistry of melatonin's interaction with reactive species. J. Pineal Res. 34, 1-10.
8. Ames B.N., Shigenaga M.K. and Hagen T.M. (1993). Oxidants, antioxidants, and the degenerative diseases of aging. Proc. Natl. Acad. Sci. USA 90, 7915-7922.
9. Andersohn F., Suissa S. and Garbe E. (2006). Use of first-and secondgeneration cyclooxygenase-2-selective nonsteroidal antiinflammatory drugs and risk of acute myocardial infarction. Circulation 113, 1950-1957.
10. Andreasson K.I., Savonenko A., Vidensky, S., Goellner J.J., Zhang Y., Shaffer A., Kaufmann W.E., Worley P.F., Isakson P. and Markowska A.L. (2001). Age-dependent cognitive deficits and neuronal apoptosis in cyclooxygenase-2 transgenic mice. J. Neurosci. 21, 8198-8209.
11. Andrabi S.A., Sayeed I., Siemen D., Wolf G., and Horn T.F. (2004). Direct inhibition of the mitochondrial permeability transition pore: a possible mechanism responsible for anti-apoptotic effects of melatonin. FASEB J. 18, 869-871.
12. Antolín I., Mayo J.C., Sainz R.M., del Brío Mde L., Herrera F., Martín V. and Rodríguez C. (2002). Protective effect of melatonin in a chronic experimental model of Parkinson's disease. Brain Res. 943, 163-173.
13. Armstrong K.J. and Niles L.P. (2002). Induction of GDNF mRNA expression by melatonin in rat C6 glioma cells. Neuroreport 13, 473-475.
14. Asanuma M. and Miyazaki I. (2007). Common anti-inflammatory drugs are potentially therapeutic for Parkinson's disease? Exp. Neurol. 206, 172-178.
15. Asomoza-Espinosa R., Alonso-López R., Mixcoatl-Zecuatl T., Aguirre-Bañuelos P., Torres-López J.E., and Granados-Soto V. (2001). Sildenafil increases diclofenac antinociception in the formalin test. Eur. J. Pharmacol. 418, 195-200.
16. Ayranci E., Altunkaynak B.Z., Aktafl A., Ragbetli M.C. and Kaplan S. (2010) Investigation of the median nerve of four week-old rats exposed to diclofenac sodium at the prenatal period. Turk. Norol. Derg. 16 (Supp 1), 193-194.
17. Batulan Z., Nalbantoglu J. and Durham H.D. (2005). Nonsteroidal antiinflammatory drugs differentially affect the heat shock response in cultured spinal cord cells. Cell Stress Chaperones. 10, 185-196.
18. Baydas G., Erçel E., Canatan H., Dönder E. and Akyol A. (2001). Effect of melatonin on oxidative status of rat brain, liver and kidney tissuesunder constant light exposure. Cell Biochem. Funct. 19, 37-41.
19. Baydas G., Nedzvetsky V.S., Nerush P.A., Kirichenko S.V., Demchenko H.M. and Reiter R.J. (2002). A novel role for melatonin: regulation of the expression of cell adhesion molecules in the rat hippocampus and cortex. Neurosci. Lett. 326, 109-112.
20. Baydas G., Kutlu S., Naziroglu M., Canpolat S., Sandal S., Ozcan M. and Kelestimur H. (2003). Inhibitory effects of melatonin on neural lipid peroxidation induced by intracerebroventricularly administered homocysteine. J. Pineal Res. 34, 36-39.
21. Baydas G., Yasar A. and Tuzcu M. (2005a). Comparison of the impact of melatonin on chronic ethanol-induced learning and memory impairment between young and aged rats. J. Pineal Res. 39, 346-352.
22. Baydas G., Reiter R.J., Akbulut M., Tuzcu M. and Tamer S. (2005b). Melatonin inhibits neural apoptosis induced by homocysteine in hippocampus of rats via inhibition of cytochrome c translocation and caspase-3 activation and by regulating pro-and anti-apoptotic protein levels. Neuroscience 135, 879-886.
23. Beck A., Krischak G., Sorg T., Augat P., Farker K., Merkel U., Kinzl L. and Claes L. (2003). Influence of diclofenac (group of nonsteroidal anti-inflammatory drugs) on fracture healing. Arch. Orthop. Trauma Surg. 123, 327-332.
24. Bezzi P., Carmignoto G., Pasti L., Vesce S., Rossi D., Rizzini B.L., Pozzan T. and Volterra A. (1998). Prostaglandins stimulate calciumdependent glutamate release in astrocytes. Nature 391, 281-285.
25. Bob P. and Fedor-Freybergh P. (2008). Melatonin, consciousness, and traumatic stress. J. Pineal Res. 44, 341-347.
26. Bokov A., Chaudhuri A. and Richardson A. (2004). The role of oxidative damage and stress in aging. Mech. Ageing Dev. 125, 811-826.
27. Bright T.P. and McNulty C.J. (1991). Suspected central nervous system toxicity from inadvertent nonsteroidal antiinflammatory drug overdose. DICP. 25, 1066-1067.
28. Brown G.C. (1999). Nitric oxide and mitochondrial respiration. Biochim. Biophys. Acta 1411, 351-369.
29. Brzozowski T. (2003). Experimental production of peptic ulcer, gastric damage and cancer models and their use in pathophysiological studies and pharmacological treatment. Polish achievements. J. Physiol. Pharmacol. 54, 99-126.
30. Brunner P., Sözer-Topcular N., Jockers R., Ravid R., Angeloni D., Fraschini F., Eckert A., Müller-Spahn F. and Savaskan E. (2006). Pineal and cortical melatonin receptors MT1 and MT2 are decreased in Alzheimer's disease. Eur. J. Histochem. 50, 311-316.
31. Butterfield D.A., Howard B.J., Yatin S., Allen K.L. and Carney J.M. (1997). Free radical oxidation of brain proteins in accelerated senescence and its modulation by N-tert-butyl-alpha-phenylnitrone. Proc. Natl. Acad. Sci. USA 94, 674-678.
32. Canan S., Aktas A., Ulkay B., Colakoglu S., Ragbetli MC., Ayyildiz M, Geuna S. and Kaplan S., (2008). Prenatal exposure to a nonsteroidal anti-inflammatory drug or saline solution impair sciatic nerve morphology: a stereological and histological study. Int. J. Dev. Neurosci. 26, 733-738.
33. Cao C., Matsumura K., Yamagata K. and Watanabe Y. (1997). Involvement of cyclooxygenase-2 in LPS-induced fever and regulation of its mRNA by LPS in the rat brain. Am. J. Physiol. 272, R1712-1725.
34. Cabeza J., Motilva V., Martín M.J. and de la Lastra C.A. (2001). Mechanisms involved in gastric protection of melatonin against oxidant stress by ischemia-reperfusion in rats. Life Sci. 68, 1405-1415.
35. Cantoni L., Valaperta R., Ponsoda X., Castell J.V., Barelli D., Rizzardini M., Mangolini A., Hauri L. and Villa P. (2003). Induction of hepatic heme oxygenase-1 by diclofenac in rodents: role of oxidative stress and cytochrome P-450 activity. J. Hepatol. 38, 776-783.
36. Capone M.L., Tacconelli S., Di Francesco L., Sacchetti A., Sciulli M.G. and Patrignani P. (2007). Pharmacodynamic of cyclooxygenase inhibitors in humans. Prostaglandins Other Lipid Mediat. 82, 85-94.
37. Cakatay U., Telci A., Kayali R., Tekeli F., Akçay T. and Sivas A. (2003). Relation of aging with oxidative protein damage parameters in the rat skeletal muscle. Clin. Biochem. 36, 51-55.
38. Catalá A. (2007). The ability of melatonin to counteract lipid peroxidation in biological membranes. Curr. Mol. Med. 7, 638-649.
39. Cardinali D.P., Rita M.N., Pereyra E. and Solveyra C.G. (1982). Role of prostaglandins in rat pineal neuroeffector junction. Changes in melatonin and norepinephrine release in vitro. Endocrinology. 111, 530-534.
40. Cardinali D.P., Furio A.M., Reyes M.P. and Brusco L.I. (2006). The use of chronobiotics in the resynchronization of the sleep-wake cycle. Cancer Causes Control. 17, 601-609.
41. Carrillo-Vico A., Calvo J.R., Abreu P., Lardone P.J., García-Mauriño S., Reiter R.J. and Guerrero J.M. (2004). Evidence of melatonin synthesis by human lymphocytes and its physiological significance: possible role as intracrine, autocrine, and/or paracrine substance. FASEB J. 18, 537-539.
42. Chan C.C., Panneton M., Taylor A.M., Therien M. and Rodger I.W. (1997). A selective inhibitor of cyclooxygenase-2 reverses endotoxin-induced pyretic responses in non-human primates. Eur. J. Pharmacol. 327, 221-225.
43. Chan L.Y., Chiu P.Y., Siu S.S. and Lau T.K. (2001). A study of diclofenac-induced teratogenicity during organogenesis using a whole rat embryo culture model. Hum. Reprod. 16, 2390-2393.
44. Chang J.K., Wang G.J., Tsai S.T. and Ho M.L. (2005a). Nonsteroidal anti-inflammatory drug effects on osteoblastic cell cycle, cytotoxicity, and cell death. Connect. Tissue Res. 46, 200-210.
45. Chang H.M., Tseng C.Y., Wei I.H., Lue J.H., Wen C.Y. and Shieh J.Y. (2005b). Melatonin restores the cytochrome oxidase reactivity in the nodose ganglia of acute hypoxic rats. J. Pineal Res. 39, 206-214.
46. Chen L.J., Gao Y.Q., Li X.J., Shen D.H. and Sun F.Y. (2005). Melatonin protects against MPTP/MPP+ -induced mitochondrial DNA oxidative damage in vivo and in vitro. J. Pineal Res. 39, 34-42.
47. Costa D., Gomes A., Reis S., Lima J.L. and Fernandes E. (2005). Hydrogen peroxide scavenging activity by non-steroidal antiinflammatory drugs. Life Sci. 76, 2841-2848.
48. Costa D., Gomes A., Lima J.L. and Fernandes E. (2008). Singlet oxygen scavenging activity of non-steroidal anti-inflammatory drugs. Redox Rep. 13, 153-160.
49. Cui J.G., Kuroda H., Chandrasekharan N.V., Pelaez R.P., Simmons D.L., Bazan N.G. and Lukiw W.J. (2004). Cyclooxygenase-3 gene expression in Alzheimer hippocampus and in stressed human neural cells. Neurochem. Res. 29, 1731-1737.
50. Cuzzocrea S., Zingarelli B., Gilad E., Hake P., Salzman A.L. and Szabó C. (1997). Protective effect of melatonin in carrageenan-induced models of local inflammation: relationship to its inhibitory effect on nitric oxide production and its peroxynitrite scavenging activity. J. Pineal Res. 23, 106-116.
51. Cuzzocrea S., Costantino G., Mazzon E., Micali A., De Sarro A. and Caputi A.P. (2000a). Beneficial effects of melatonin in a rat model of splanchnic artery occlusion and reperfusion. J. Pineal Res. 28, 52-63.
52. Cuzzocrea S., Costantino G., Gitto E., Mazzon E., Fulia F., Serraino I., Cordaro S., Barberi I., De Sarro A. and Caputi A.P. (2000b). Protective effects of melatonin in ischemic brain injury. J. Pineal Res. 29, 217-227.
53. Cuzzocrea S. and Reiter R.J. (2001). Pharmacological action of melatonin in shock, inflammation and ischemia/reperfusion injury. Eur. J. Pharmacol. 426, 1-10.
54. Dairam A., Antunes E.M., Saravanan K.S. and Daya S. (2006). Nonsteroidal anti-inflammatory agents, tolmetin and sulindac, inhibit liver tryptophan 2,3-dioxygenase activity and alter brain neurotransmitter levels. Life Sci. 79, 2269-7224.
55. Davey P.G. (1988). Overview of drug interactions with the quinolones. J. Antimicrob. Chemother. 22 (Suppl C), 97-107.
56. Davies M.J. (2005). The oxidative environment and protein damage. Biochim. Biophys. Acta 1703, 93-109.
57. De Meira Santos Lima M., Braga Reksidler A., Marques Zanata S., Bueno Machado H., Tufik S. and Vital M.A. (2006). Different parkinsonism models produce a time-dependent induction of COX-2 in the substantia nigra of rats. Brain Res. 1101, 117-125.
58. Demple B., Herman T. and Chen D.S. (1991). Cloning and expression of APE, the cDNA encoding the major human apurinic endonuclease: definition of a family of DNA repair enzymes. Proc. Natl. Acad. Sci. U.S.A. 88, 11450-11454.
59. Doetsch P.W. and Cunningham R.P. (1990). The enzymology of apurinic/apyrimidinic endonucleases. Mutat. Res. 236, 173-201.
60. Djeridane Y., Vivien-Roels B., Simonneaux V., Miguez J.M. and Pévet P. (1998). Evidence for melatonin synthesis in rodent Harderian gland: a dynamic in vitro study. J. Pineal Res. 25, 54-64.
61. Dubocovich M.L. (1988). Pharmacology and function of melatonin receptors. FASEB J. 2, 2765-2773.
62. Dubocovich M.L. and Markowska M. (2005). Functional MT1 and MT2 melatonin receptors in mammals. Endocrine 27, 101-110.
63. Dubocovich M.L., Rivera-Bermudez M.A., Gerdin M.J. and Masana M.I. (2003). Molecular pharmacology, regulation and function of mammalian melatonin receptors. Front. Biosci. 8, d1093-1108.
64. Dröge W. (2002). Free radicals in the physiological control of cell function. Physiol. Rev. 82, 47-95.
65. El-Aziz M.A., Hassan H.A., Mohamed M.H., Meki A.R., Abdel-Ghaffar S.K. and Hussein M.R. (2005). The biochemical and morphological alterations following administration of melatonin, retinoic acid and Nigella sativa in mammary carcinoma: an animal model. Int. J. Exp. Pathol. 86, 383-396.
66. El-Sherif Y., Tesoriero J., Hogan M.V. and Wieraszko A. (2003). Melatonin regulates neuronal plasticity in the hippocampus. J. Neurosci. Res. 72, 454-460.
67. El-Sokkary G.H., Kamel E.S. and Reiter R.J. (2003). Prophylactic effect of melatonin in reducing lead-induced neurotoxicity in the rat. Cell. Mol. Biol. Lett. 8, 461-470.
68. Elsisi N.S., Darling-Reed S., Lee E.Y., Oriaku E.T. and Soliman K.F. (2005). Ibuprofen and apigenin induce apoptosis and cell cycle arrest in activated microglia. Neurosci. Lett. 375, 91-96.
69. Ericson A. and Källén B.A. (2001). Nonsteroidal anti-inflammatory drugs in early pregnancy. Reprod. Toxicol. 15, 371-375.
70. Esposito E., Di Matteo V., Benigno A., Pierucci M., Crescimanno G. and Di Giovanni G. (2007). Non-steroidal anti-inflammatory drugs in Parkinson's disease. Exp. Neurol. 205, 295-312.
71. Eskiocak S., Tutunculer F., Basaran U.N., Taskiran A. and Cakir E. (2007). The effect of melatonin on protein oxidation and nitric oxide in the brain tissue of hypoxic neonatal rats. Brain Dev. 29, 19-24.
72. Feng Z., Qin C., Chang Y. and Zhang J.T. (2006). Early melatonin supplementation alleviates oxidative stress in a transgenic mouse model of Alzheimer's disease. Free Radic. Biol. Med. 40, 101-109.
73. Fernandes E., Costa D., Toste S.A., Lima J.L. and Reis S. (2004). In vitro scavenging activity for reactive oxygen and nitrogen species by nonsteroidal anti-inflammatory indole, pyrrole, and oxazole derivative drugs. Free Radic. Biol. Med. 37, 1895-1905.
74. Finkel T. and Holbrook N.J. (2000). Oxidants, oxidative stress and the biology of ageing. Nature 408, 239-247.
75. Fosslien E. (2001). Mitochondrial medicine-molecular pathology of defective oxidative phosphorylation. Ann. Clin. Lab. Sci. 31, 25-67.
76. Foster C.E., Bianchet M.A., Talalay P., Faig M. and Amzel L.M. (2000). Structures of mammalian cytosolic quinone reductases. Free Radic. Biol. Med. 29, 241-245.
77. Gilad E., Cuzzocrea S., Zingarelli B., Salzman A.L. and Szabó C. (1997). Melatonin is a scavenger of peroxynitrite. Life Sci. 60, 169-174.
78. Gitto E., Pellegrino S., Gitto P., Barberi I. and Reiter R.J. (2009). Oxidative stress of the newborn in the pre-and postnatal period and the clinical utility of melatonin. J. Pineal Res. 46, 128-139.
79. Giusti P., Gusella M., Lipartiti M., Milani D., Zhu W., Vicini S. and Manev H. (1995). Melatonin protects primary cultures of cerebellar granule neurons from kainate but not from N-methyl-D-aspartate excitotoxicity. Exp. Neurol. 131, 39-46.
80. Gokcimen A., Ragbetli M.C., Bafl O., Tunc A.T., Aslan H., Yazici A.C. and Kaplan S. (2007). Effect of prenatal exposure to an antiinflammatory drug on neuron number in cornu ammonis and dentate gyrus of the rat hippocampus: A stereological study. Brain Res. 1127, 185-192.
81. Gómez-Lechón M.J., Ponsoda X., O'Connor E., Donato T., Castell J.V. and Jover R. (2003). Diclofenac induces apoptosis in hepatocytes by alteration of mitochondrial function and generation of ROS. Biochem. Pharmacol. 66, 2155-2167.
82. Granados-Soto V., Argüelles C.F. and Ortiz M.I. (2002). The peripheral antinociceptive effect of resveratrol is associated with activation of potassium channels. Neuropharmacology 43, 917-923.
83. Guven A., Yavuz O., Cam M., Ercan F., Bukan N. and Comunoglu C. (2007). Melatonin protects against epirubicin-induced cardiotoxicity. Acta Histochem. 109, 52-60.
84. Halliwell B. and Cutteridge J.M.C. (1985). Oxygen radicals and the nervous system. Trends Neurosci. 8, 22-26.
85. Halliwell B. (1992). Reactive oxygen species and the central nervous system. J. Neurochem. 59, 1609-1623.
86. Han Z., Pantazis P., Wyche J.H., Kouttab N., Kidd V.J. and Hendrickson E.A. (2001). A Fas-associated death domain protein-dependent mechanism mediates the apoptotic action of non-steroidal antiinflammatory drugs in the human leukemic Jurkat cell line. J. Biol. Chem. 276, 38748-38754.
87. Hardeland R. (2005). Antioxidative protection by melatonin: multiplicity of mechanisms from radical detoxification to radical avoidance. Endocrine 27, 119-130.
88. Hardeland R. and Pandi-Perumal S.R. (2005). Melatonin, a potent agent in antioxidative defense: actions as a natural food constituent, gastrointestinal factor, drug and prodrug. Nutr. Metab. (Lond). 2, 22.
89. Hardeland R., Backhaus C. and Fadavi A. (2007). Reactions of the NO redox forms NO+, •NO and HNO (protonated NO-) with the melatonin metabolite N1-acetyl-5-methoxykynuramine. J. Pineal Res. 43, 382-388.
90. Hickey E.J., Raje R.R., Reid V.E., Gross S.M. and Ray S.D. (2001). Diclofenac induced in vivo nephrotoxicity may involve oxidative stress-mediated massive genomic DNA fragmentation and apoptotic cell death. Free Radic. Biol. Med. 31, 139-152.
91. Hill J.M. and Switzer R.C. 3rd. (1984). The regional distribution and cellular localization of iron in the rat brain. Neuroscience. 11, 595-603.
92. Hirst W.D., Young K.A., Newton R., Allport V.C., Marriott D.R. and Wilkin G.P. (1999). Expression of COX-2 by normal and reactive astrocytes in the adult rat central nervous system. Mol. Cell. Neurosci. 13, 57-68.
93. Hoozemans J.J., Rozemuller A.J., Janssen I., De Groot C.J., Veerhuis R. and Eikelenboom P. (2001). Cyclooxygenase expression in microglia and neurons in Alzheimer's disease and control brain. Acta Neuropathol. 101, 2-8.
94. Hussein M.R., Abu-Dief E.E., Abd El-Reheem M.H. and Abd-Elrahman A. (2005). Ultrastructural evaluation of the radioprotective effects of melatonin against X-ray-induced skin damage in Albino rats. Int. J. Exp. Pathol. 86, 45-55.
95. Inoue A., Muranaka S., Fujita H., Kanno T., Tamai H. and Utsumi K. (2004). Molecular mechanism of diclofenac-induced apoptosis of promyelocytic leukemia: dependency on reactive oxygen species, Akt, Bid, cytochrome and caspase pathway. Free Radic. Biol. Med. 37, 1290-1299.
96. Itoh M.T., Ishizuka B., Kudo Y., Fusama S., Amemiya A. and Sumi Y. (1997). Detection of melatonin and serotonin N-acetyltransferase and hydroxyindole-O-methyltransferase activities in rat ovary. Mol. Cell. Endocrinol. 136, 7-13.
97. Jimenez-Jorge S., Guerrero J.M., Jimenez-Caliani A.J., Naranjo M.C., Lardone P.J., Carrillo-Vico A., Osuna C. and Molinero P. (2007). Evidence for melatonin synthesis in the rat brain during development. J. Pineal Res. 42, 240-246.
98. Jolly C. and Morimoto R.I. (2000). Role of the heat shock response and molecular chaperones in oncogenesis and cell death. J. Natl. Cancer Inst. 92, 1564-1572.
99. Kelly S., Bieneman A., Horsburgh K., Hughes D., Sofroniew M.V., McCulloch J. and Uney J.B. (2001). Targeting expression of hsp70i to discrete neuronal populations using the Lmo-1 promoter: assessment of the neuroprotective effects of hsp70i in vivo and in vitro. J. Cereb. Blood Flow Metab. 21, 972-981.
100. Kiliç I., Kiliç B.A., Güven C., Demirpençe E. and Akflit M.A. (2000). Role of nitric oxide in hypoxia-induced changes in newborn rats. Biol. Neonate 78, 191-197.
101. Klc O., Horasanl E., Demir T., Han Ö., Kara C., Pala Y. and Dikmen B. (2004). Is epidural diclofenac sodium neurotoxic? Reg. Anesth Pain. Med. 29, (Supplement 2), 14.
102. Klampfer L., Cammenga J., Wisniewski H.G. and Nimer S.D. (1999). Sodium salicylate activates caspases and induces apoptosis of myeloid leukemia cell lines. Blood. 93, 2386-2394.
103. Kirik D., Georgievska B. and Björklund A. (2004). Localized striatal delivery of GDNF as a treatment for Parkinson disease. Nat. Neurosci. 7, 105-110.
104. Kirkup A.J., Edwards G., Green M.E., Miller M., Walker S.D. and Weston A.H. (1996). Modulation of membrane currents and mechanical activity by niflumic acid in rat vascular smooth muscle. Eur. J. Pharmacol. 317, 165-174.
105. Kokoszka J.E., Coskun P., Esposito L.A. and Wallace D.C. (2001). Increased mitochondrial oxidative stress in the Sod2 (+/-) mouse results in the age-related decline of mitochondrial function culminating in increased apoptosis. Proc. Natl. Acad. Sci. USA 98, 2278-2283.
106. Konturek S.J., Konturek P.C., Brzozowski T. and Bubenik G.A. (2007). Role of Melatonin in upper gastrointestinal tract. Journal of Physiology and Pharmacology. 58, 23-52.
107. Kopp E. and Ghosh S. (1994). Inhibition of NF-kappa B by sodium salicylate and aspirin. Science. 265, 956-959.
108. Kudo C., Kori M., Matsuzaki K., Yamai K., Nakajima A., Shibuya A., Niwa H., Kamisaki Y. and Wada K. (2003). Diclofenac inhibits proliferation and differentiation of neural stem cells. Biochem. Pharmacol. 66, 289-295.
109. Kulkarni S.K. and Naidu P.S. (2003). Pathophysiology and drug therapy of tardive dyskinesia: Current concepts and future perspectives. Drugs Today (Barc), 39, 19-49.
110. Kusuhara H., Matsuyuki H., Matsuura M., Imayoshi T., Okumoto T. and Matsui H. (1998). Induction of apoptotic DNA fragmentation by nonsteroidal anti-inflammatory drugs in cultured rat gastric mucosal cells. Eur. J. Pharmacol. 360, 273-280.
111. Kusuhara H., Komatsu H., Sumichika H. and Sugahara K. (1999). Reactive oxygen species are involved in the apoptosis induced by nonsteroidal anti-inflammatory drugs in cultured gastric cells. Eur. J. Pharmacol. 383, 331-337.
112. Kusunoki N., Yamazaki R. and Kawai S. (2002). Induction of apoptosis in rheumatoid synovial fibroblasts by celecoxib, but not by other selective cyclooxygenase 2 inhibitors. Arthritis Rheum. 46, 3159-3167.
113. Ladizesky M.G., Boggio V., Albornoz L.E., Castrillón P.O., Mautalen C. and Cardinali D.P. (2003). Melatonin increases oestradiol-induced bone formation in ovariectomized rats. J. Pineal Res. 34, 143-151.
114. Ladizesky M.G., Boggio V., Cutrera R.A., Mondelo N., Mastaglia S., Somoza J. and Cardinali D.P. (2006). Melatonin effect on bone metabolism in rats treated with methylprednisolone. J. Pineal Res. 40, 297-304.
115. Leaden P.J. and Catalá A. (2005). Protective effect of melatonin on ascorbate-Fe2+ lipid peroxidation of polyunsaturated fatty acids in rat liver, kidney and brain microsomes: a chemiluminescence study. J. Pineal Res. 39, 164-169.
116. Lee Y.T. and Wang Q. (1999). Inhibition of hKv2.1, a major human neuronal voltage-gated K+ channel, by meclofenamic acid. Eur. J. Pharmacol. 378, 349-356.
117. Lee J.E., Yenari M.A., Sun G.H., Xu L., Emond M.R., Cheng D., Steinberg G.K. and Giffard R.G. (2001). Differential neuroprotection from human heat shock protein 70 overexpression in in vitro and in vivo models of ischemia and ischemia-like conditions. Exp. Neurol. 170, 129-139.
118. Lee H.M., Kim H.I., Shin Y.K., Lee C.S., Park M. and Song J.H. (2003). Diclofenac inhibition of sodium currents in rat dorsal root ganglion neurons. Brain Res. 992, 120-127.
119. Leon J., Acuña-Castroviejo D., Sainz R.M., Mayo J.C., Tan D.X. and Reiter R.J. (2004). Melatonin and mitochondrial function. Life Sci. 75, 765-790.
120. León J., Acuña-Castroviejo D., Escames G., Tan D.X. and Reiter R.J. (2005). Melatonin mitigates mitochondrial malfunction. J. Pineal Res. 38, 1-9.
121. Letechipía-Vallejo G., López-Loeza E., Espinoza-González V., González-Burgos I., Olvera-Cortés M.E., Moralí G. and Cervantes M. (2007). Long-term morphological and functional evaluation of the neuroprotective effects of post-ischemic treatment with melatonin in rats. J. Pineal Res. 42, 139-146.
122. Li S., Wang Y., Matsumura K., Ballou L.R., Morham S.G. and Blatteis C.M. (1999). The febrile response to lipopolysaccharide is blocked in cyclooxygenase-2-/-, but not in cyclooxygenase-1-/-mice. Brain Res. 825, 86-94.
123. Lin A.M. and Ho L.T. (2000). Melatonin suppresses iron-induced neurodegeneration in rat brain. Free Radic. Biol. Med. 28, 904-911.
124. Liu L.Y., Fei X.W., Li Z.M., Zhang Z.H. and Mei Y.A. (2005). Diclofenac, a nonsteroidal anti-inflammatory drug, activates the transient outward K+ current in rat cerebellar granule cells. Neuropharmacology 48, 918-926.
125. Lu X., Xie W., Reed D., Bradshaw W.S. and Simmons D.L. (1995). Nonsteroidal antiinflammatory drugs cause apoptosis and induce cyclooxygenases in chicken embryo fibroblasts. Proc. Natl. Acad. Sci. USA 92, 7961-7965.
126. Mahal H.S., Sharma H.S. and Mukherjee T. (1999). Antioxidant properties of melatonin: a pulse radiolysis study. Free Radic. Biol. Med. 26, 557-565.
127. Makker K., Agarwal A. and Sharma R. (2009). Oxidative stress & male infertility. Indian J. Med. Res. 129, 357-367.
128. Maldonado M.D., Murillo-Cabezas F., Terron M.P, Flores L.J., Tan D.X., Manchester L.C. and Reiter R.J. (2007). The potential of melatonin in reducing morbidity-mortality after craniocerebral trauma. J. Pineal Res. 42, 1-11.
129. Manda K., Ueno M. and Anzai K. (2007). AFMK, a melatonin metabolite, attenuates X-ray-induced oxidative damage to DNA, proteins and lipids in mice. J. Pineal Res. 42, 386-393.
130. Martín M., Macías M., Escames G., Reiter R.J., Agapito M.T., Ortiz G.G. and Acuña-Castroviejo D. (2000). 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, 242-248.
131. Martín M., Macías M., León J., Escames G., Khaldy H. and Acuña-Castroviejo D. (2002). Melatonin increases the activity of the oxidative phosphorylation enzymes and the production of ATP in rat brain and liver mitochondria. Int. J. Biochem. Cell Biol. 34, 348-357.
132. Mazzon E., Esposito E., Crisafulli C., Riccardi L., Muià C., Di Bella P., Meli R. and Cuzzocrea S. (2006). Melatonin modulates signal transduction pathways and apoptosis in experimental colitis. J. Pineal Res. 41, 363-373.
133. Mogulkoc R., Baltaci A.K., Oztekin E., Aydin L. and Sivrikaya A. (2006). Melatonin prevents oxidant damage in various tissues of rats with hyperthyroidism. Life Sci. 79, 311-315.
134. Mohanakumar K.P., Muralikrishnan D. and Thomas B. (2000). Neuroprotection by sodium salicylate against 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine-induced neurotoxicity. Brain Res. 864, 281-290.
135. Monnet F.P. (2002). Melatonin modulates [3H] serotonin release in the rat hippocampus: effects of circadian rhythm. J. Neuroendocrinol. 14, 194-199.
136. Morimoto R.I. (1998). Regulation of the heat shock transcriptional response: cross talk between a family of heat shock factors, molecular chaperones, and negative regulators. Genes Dev. 12, 3788-3796.
137. Morioka N., Kumagai K., Morita K., Kitayama S. and Dohi T. (2004). Nonsteroidal anti-inflammatory drugs potentiate 1-methyl-4-phenylpyridinium (MPP+)-induced cell death by promoting the intracellular accumulation of MPP+ in PC12 cells. J. Pharmacol. Exp. Ther. 310, 800-807.
138. Mosser D.D. and Morimoto R.I. (2004). Molecular chaperones and the stress of oncogenesis. Oncogene. 23, 2907-2918.
139. Muramatsu K., Sheldon R.A., Black S.M., Täuber M. and Ferriero D.M. (2000). Nitric oxide synthase activity and inhibition after neonatal hypoxia ischemia in the mouse brain. Brain Res. Dev. Brain Res. 123, 119-127.
140. Murphy P.J., Myers B.L. and Badia P. (1996). Nonsteroidal antiinflammatory drugs alter body temperature and suppress melatonin in humans. Physiol. Behav. 59, 133-139.
141. Naesh O. (2006). Back to the future: postoperative pain management beyond COX-2 inhibitors. N. Z. Med. J. 119, 1-11.
142. Nagai R., Watanabe K., Wakatsuki A., Hamada F., Shinohara K., Hayashi Y., Imamura R. and Fukaya T. (2008). Melatonin preserves fetal growth in rats by protecting against ischemia/reperfusioninduced oxidative/nitrosative mitochondrial damage in the placenta. J. Pineal Res. 45, 271-276.
143. Noda Y., Mori A., Liburdy R. and Packer L. (1999). Melatonin and its precursors scavenge nitric oxide. J. Pineal Res. 27, 159-163.
144. Nohl H., Gille L. and Staniek K. (2005). Intracellular generation of reactive oxygen species by mitochondria. Biochem. Pharmacol. 69, 719-723.
145. Odaci E. and Kaplan S. (2009). Melatonin and nerve regeneration. Int. Rev. Neurobiol. 87, 317-335.
146. Ortiz M.I., Torres-López J.E., Castañeda-Hernández G., Rosas R., Vidal-Cantú G.C. and Granados-Soto V. (2002). Pharmacological evidence for the activation of K+ channels by diclofenac. Eur. J. Pharmacol. 438, 85-91.
147. Osuna C., Reiter R.J., García J.J., Karbownik M., Tan D.X., Calvo J.R. and Manchester L.C. (2002). Inhibitory effect of melatonin on homocysteine-induced lipid peroxidation in rat brain homogenates. Pharmacol. Toxicol. 90, 32-37.
148. Pääkkönen T., Mäkinen T.M., Leppäluoto J., Vakkuri O., Rintamäki H., Palinkas L.A., and Hassi J. (2006). Urinary melatonin: a noninvasive method to follow human pineal function as studied in three experimental conditions. J. Pineal Res. 40, 110-115.
149. Pandi-Perumal S.R., Srinivasan V., Maestroni G.J., Cardinali D.P., Poeggeler B. and Hardeland R. (2006). Melatonin: Nature's most versatile biological signal? FEBS J. 273, 2813-2838.
150. Pei Z., Ho H.T. and Cheung R.T. (2002). Pre-treatment with melatonin reduces volume of cerebral infarction in a permanent middle cerebral artery occlusion stroke model in the rat. Neurosci. Lett. 318, 141-144.
151. Pieri C., Marra M., Moroni F., Recchioni R. and Marcheselli F. (1994). Melatonin: a peroxyl radical scavenger more effective than vitamin E. Life Sci. 55, PL271-276.
152. Piqué M., Barragán M., Dalmau M., Bellosillo B., Pons G. and Gil J. (2000). Aspirin induces apoptosis through mitochondrial cytochrome c release. FEBS Lett. 480, 193-196.
153. Poeggeler B., Saarela S., Reiter R.J., Tan D.X., Chen L.D., Manchester L.C. and Barlow-Walden L.R. (1994). Melatonin--a highly potent endogenous radical scavenger and electron donor: new aspects of the oxidation chemistry of this indole accessed in vitro. Ann. NY Acad. Sci. 738, 419-420.
154. Pozo D., Reiter R.J., Calvo J.R. and Guerrero J.M. (1997). Inhibition of cerebellar nitric oxide synthase and cyclic GMP production by melatonin via complex formation with calmodulin. J. Cell. Biochem. 65, 430-442.
155. Ragbetli M.C., Ozyurt B., Aslan H., Odaci E., Gokcimen A., Sahin B. and Kaplan S. (2007). Effect of prenatal exposure to diclofenac sodium on Purkinje cell numbers in rat cerebellum: a stereological study. Brain Res. 1174, 130-135.
156. Rahman I., Biswas S.K., Kode A. (2006). Oxidant and antioxidant balance in the airways and airway diseases. Eur. J. Pharmacol. 533, 222-239.
157. Ravagnan L., Gurbuxani S., Susin S.A., Maisse C., Daugas E., Zamzami N., Mak T., Jäättelä M., Penninger J.M., Garrido C. and Kroemer G. (2001). Heat-shock protein 70 antagonizes apoptosisinducing factor. Nat. Cell Biol. 3, 839-343.
158. Reiter R.J. (1998). Oxidative damage in the central nervous system: protection by melatonin. Prog. Neurobiol. 56, 359-384.
159. Reiter R.J. (2003). Melatonin: clinical relevance. Best Pract. Res. Clin. Endocrinol. Metab. 17, 273-285.
160. Reiter R.J., Melchiorri D., Sewerynek E., Poeggeler B., Barlow-Walden L., Chuang J., Ortiz G.G. and Acuña-Castroviejo D. (1995). A review of the evidence supporting melatonin's role as an antioxidant. J. Pineal Res. 18, 1-11.
161. Reiter R., Tang L., Garcia J.J. and Muñoz-Hoyos A. (1997). Pharmacological actions of melatonin in oxygen radical pathophysiology. Life Sci. 60, 2255-2271.
162. Reiter R.J. and Maestroni GJ. (1999). Melatonin in relation to the antioxidative defense and immune systems: possible implications for cell and organ transplantation. J. Mol. Med. 77, 36-39.
163. Reiter R.J., Tan D.X., Osuna C. and Gitto E. (2000). Actions of melatonin in the reduction of oxidative stress. A review. J. Biomed. Sci. 7, 444-458.
164. Reiter R.J., Acuña-Castroviejo D., Tan D.X. and Burkhardt S. (2001a) Free radical-mediated molecular damage. Mechanisms for the protective actions of melatonin in the central nervous system. Ann. NY Acad. Sci. 939, 200-215.
165. Reiter R.J., Tan D.X., Manchester L.C. and Qi W. (2001b). Biochemical reactivity of melatonin with reactive oxygen and nitrogen species: a review of the evidence. Cell Biochem. Biophys. 34, 237-256.
166. Reiter R.J., Tan D.X. and Burkhardt S. (2002). Reactive oxygen and nitrogen species and cellular and organismal decline: amelioration with melatonin. Mech. Ageing Dev. 123, 1007-1019.
167. Reiter R.J., Tan D.X., Manchester L.C., Simopoulos A.P., Maldonado M.D., Flores L.J., and Terron M.P. (2007a). Melatonin in edible plants (phytomelatonin): Identification, concentrations, bioavailability and proposed functions. World Rev. Nutr. Diet. 97, 211-230.
168. Reiter R.J., Tan D.X., Terron M.P., Flores L.J. and Czarnocki Z. (2007b). Melatonin and its metabolites: new findings regarding their production and their radical scavenging actions. Acta Biochim. Pol. 54, 1-9.
169. Robson C.N. and Hickson I.D. (1991). Isolation of cDNA clones encoding a human apurinic/apyrimidinic endonuclease that corrects DNA repair and mutagenesis defects in E. coli xth (exonuclease III) mutants. Nucleic Acids Res. 19, 5519-5523.
170. Robson C.N., Milne A.M., Pappin D.J. and Hickson I.D. (1991). Isolation of cDNA clones encoding an enzyme from bovine cells that repairs oxidative DNA damage in vitro: homology with bacterial repair enzymes. Nucleic Acids Res. 19, 1087-1092.
171. Rodriguez C., Mayo J.C., Sainz R.M., Antolín I., Herrera F., Martín V. and Reiter RJ. (2004). Regulation of antioxidant enzymes: a significant role for melatonin. J. Pineal Res. 36, 1-9.
172. Rodríguez M.I., Escames G., López L.C., López A., García J.A., Ortiz F. and Acuña-Castroviejo D. (2007). Chronic melatonin treatment reduces the age-dependent inflammatory process in senescenceaccelerated mice. J. Pineal Res. 42, 272-279.
173. Russell R.I. (2001). Non-steroidal anti-inflammatory drugs and gastrointestinal damage-problems and solutions. Postgrad. Med. J. 77, 82-88.
174. Sahagan B.G., Stephenson D.T., Hounslow N., Liston D.R. and Manning P.T. (2005). Killing pain, not neurons. Nat Med. 11, 817-818
175. Sairam K., Saravanan K.S., Banerjee R. and Mohanakumar K.P. (2003). Non-steroidal anti-inflammatory drug sodium salicylate, but not diclofenac or celecoxib, protects against 1-methyl-4-phenyl pyridinium-induced dopaminergic neurotoxicity in rats. Brain Res. 966, 245-252.
176. Sanzgiri R.P., Araque A. and Haydon P.G. (1999). Prostaglandin E2 stimulates glutamate receptor-dependent astrocyte neuromodulation in cultured hippocampal cells. J. Neurobiol. 41, 221-229.
177. Savaser A., Ozkan Y. and Iflimer A. (2005). Preparation and in vitro evaluation of sustained release tablet formulations of diclofenac sodium. Farmaco. 60, 171-177.
178. Savaskan E., Olivieri G., Brydon L., Jockers R., Kräuchi K., Wirz-Justice A. and Müller-Spahn F. (2001). Cerebrovascular melatonin MT1-receptor alterations in patients with Alzheimer's disease. Neurosci. Lett. 308, 9-12.
179. Savaskan E., Olivieri G., Meier F., Brydon L., Jockers R., Ravid R., Wirz-Justice A., Müller-Spahn F. (2002). Increased melatonin 1areceptor immunoreactivity in the hippocampus of Alzheimer's disease patients. J. Pineal Res. 32, 59-62.
180. Savaskan E., Ayoub M.A., Ravid R., Angeloni D., Fraschini F., Meier F., Eckert A., Müller-Spahn F. and Jockers R. (2005). Reduced hippocampal MT2 melatonin receptor expression in Alzheimer's disease. J. Pineal Res. 38, 10-16.
181. Scholer D.W., Ku E.C., Boettcher I. and Schweizer A. (1986). Pharmacology of diclofenac sodium. Am. J. Med. 80, 34-38.
182. Segev S., Rehavi M. and Rubinstein E. (1988). Quinolones, theophylline, and diclofenac interactions with the gammaaminobutyric acid receptor. Antimicrob. Agents Chemother. 32, 1624-1626.
183. Sener G., Sert G., Sehirli AO., Arbak S., Gedik N. and Ayanoglu-Dülger G. (2006). Melatonin protects against pressure ulcer-induced oxidative injury of the skin and remote organs in rats. J. Pineal Res. 40, 280-287.
184. Sharma R., McMillan C.R., Tenn C.C. and Niles L.P. (2006). Physiological neuroprotection by melatonin in a 6-hydroxydopamine model of Parkinson's disease. Brain Res. 1068, 230-236.
185. Shaw T., Lee R.J. and Partridge L.D. (1995). Action of diphenylamine carboxylate derivatives, a family of non-steroidal anti-inflammatory drugs, on [Ca2+]i and Ca(2+)-activated channels in neurons. Neurosci. Lett. 190, 121-124.
186. Sies H. (1997). Oxidative stress: oxidants and antioxidants. Exp. Physiol. 82, 291-295.
187. Siu S.S., Yeung J.H. and Lau T.K. (2000). A study on placental transfer of diclofenac in first trimester of human pregnancy. Hum. Reprod. 15, 2423-2425.
188. Siu K.L. and Lee W.H. (2004). Maternal diclofenac sodium ingestion and severe neonatal pulmonary hypertension. J. Paediatr. Child Health. 40, 152-153.
189. Siu A.W., Maldonado M., Sanchez-Hidalgo M., Tan D.X. and Reiter RJ. (2006). Protective effects of melatonin in experimental free radicalrelated ocular diseases. J. Pineal Res. 40, 101-109.
190. Slominski A., Pisarchik A., Semak I., Sweatman T., Wortsman J., Szczesniewski A., Slugocki G., McNulty J., Kauser S., Tobin D.J., Jing C. and Johansson O. (2002). Serotoninergic and melatoninergic systems are fully expressed in human skin. FASEB J. 16, 896-898.
191. Smith A.D., Kozlowski D.A., Bohn M.C. and Zigmond M.J. (2005). Effectof AdGDNF on dopaminergic neurotransmission in the striatum of 6-OHDA-treated rats. Exp. Neurol. 193, 420-426.
192. Srinivasan V., Pandi-Perumal S.R., Cardinali D.P., Poeggeler B. and Hardeland R. (2006). Melatonin in Alzheimer's disease and other neurodegenerative disorders. Behav. Brain Funct. 2, 15.
193. Stadtman E.R. and Levine R.L. (2003). Free radical-mediated oxidation of free amino acids and amino acid residues in proteins. Amino Acids. 25, 207-218.
194. Stark L.A. and Dunlop M.G. (2005). Nucleolar sequestration of RelA (p65) regulates NF-kappaB-driven transcription and apoptosis. Mol. Cell Biol. 25, 5985-6004.
195. Subbaramaiah K., Chung W.J., Michaluart P., Telang N., Tanabe T., Inoue H., Jang M., Pezzuto J.M. and Dannenberg A.J. (1998). Resveratrol inhibits cyclooxygenase-2 transcription and activity in phorbol ester-treated human mammary epithelial cells. J. Biol. Chem. 273, 21875-21882.
196. Suresh C., Dennis A.O., Heinz J., Vemuri M.C. and Chetty C.S. (2006). Melatonin protection against lead-induced changes in human neuroblastoma cell cultures. Int. J. Toxicol. 25, 459-464.
197. Surrall K., Smith J.A., Bird H., Okala B., Othman H. and Padwick D.J. (1987). Effect of ibuprofen and indomethacin on human plasma melatonin. J. Pharm. Pharmacol. 39, 840-843.
198. Szczepanik M. (2007). Melatonin and its influence on immune system. J Physiol Pharmacol. 58, 115-24.
199. Tan D.X., Chen L.D., Poeggeler B., Manchester L.C. and Reiter R.J., (1993). Melatonin: a potent, endogenous hydroxyl radical scavenger. Endocr. J. 1, 57-60.
200. Tan D.X., Manchester L.C., Reiter R.J., Qi W., Kim S.J. and El-Sokkary GH. (1998). Melatonin protects hippocampal neurons in vivo against kainic acid-induced damage in mice. J. Neurosci. Res. 54, 382-389.
201. Tan D.X., Manchester L.C., Terron M.P., Flores L.J. and Reiter RJ. (2007). One molecule, many derivatives: a never-ending interaction of melatonin with reactive oxygen and nitrogen species? J. Pineal Res. 42, 28-42.
202. Teismann P. and Ferger B. (2001). Inhibition of the cyclooxygenase isoenzymes COX-1 and COX-2 provide neuroprotection in the MPTP-mouse model of Parkinson's disease. Synapse 39, 167-174.
203. Teismann P., Tieu K., Choi D.K., Wu D.C., Naini A., Hunot S., Vila M., Jackson-Lewis V. and Przedborski S. (2003). Cyclooxygenase-2 is instrumental in Parkinson's disease neurodegeneration. Proc. Natl. Acad. Sci. USA 100, 5473-5478.
204. Thomas L., Purvis C.C., Drew J.E., Abramovich D.R. and Williams L.M. (2002). Melatonin receptors in human fetal brain: 2-[(125)I] iodomelatonin binding and MT1 gene expression. J. Pineal Res. 33, 218-224.
205. Ton T.G., Heckbert S.R., Longstreth W.T.J., Rossing M.A., Kukull W.A., Franklin G.M., Swanson P.D., Smith-Weller T. and Checkoway H. (2006). Nonsteroidal anti-inflammatory drugs and risk of Parkinson's disease. Mov. Disord. 21, 964-969.
206. Toninello A., Salvi M. and Mondovì B. (2004). Interaction of biologically active amines with mitochondria and their role in the mitochondrialmediated pathway of apoptosis. Curr. Med. Chem. 11, 2349-2374.
207. Touitou Y. (2001). Human aging and melatonin. Clinical relevance. Exp. Gerontol. 36, 1083-1100.
208. Turgut M., Erdogan S., Ergin K. and Serter M. (2007). Melatonin ameliorates blood-brain barrier permeability, glutathione, and nitric oxide levels in the choroid plexus of the infantile rats with kaolininduced hydrocephalus. Brain Res. 1175, 117-125.
209. Tütüncüler F., Eskiocak S., Baflaran U.N., Ekuklu G., Ayvaz S. and Vatansever U. (2005). The protective role of melatonin in experimental hypoxic brain damage. Pediatr. Int. 47, 434-439.
210. Uz T., Giusti P., Franceschini D., Kharlamov A. and Manev H. (1996). Protective effect of melatonin against hippocampal DNA damage induced by intraperitoneal administration of kainate to rats. Neuroscience. 73, 631-636.
211. Uz T., Arslan A.D., Kurtuncu M., Imbesi M., Akhisaroglu M., Dwivedi Y., Pandey G.N. and Manev H. (2005). The regional and cellular expression profile of the melatonin receptor MT1 in the central dopaminergic system. Brain Res. Mol. Brain Res. 136, 45-53.
212. Vane J.R. (1971). Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat. New. Biol. 231, 232-235.
213. Voisin P., Van Camp G., Pontoire C. and Collin J.P. (1993). Prostaglandins stimulate serotonin acetylation in chick pineal cells: involvement of cyclic AMP-dependent and calcium/calmodulindependent mechanisms. J. Neurochem. 60, 666-670.
214. Voilley N., de Weille J., Mamet J. and Lazdunski M. (2001). Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors. J. Neurosci. 21, 8026-8033.
215. Wakamatsu T., Dogru M., Tsubota K. (2008). Tearful relations: oxidative stress, inflammation and eye diseases. Arq. Bras. Oftalmol. 71, 72-79.
216. Wallace J.L. (2007). Building a better aspirin: gaseous solutions to a century-old problem. Br. J. Pharmacol. 152, 421-428.
217. Witt-Enderby P.A., Radio N.M., Doctor J.S. and Davis V.L. (2006). Therapeutic treatments potentially mediated by melatonin receptors: potential clinical uses in the prevention of osteoporosis, cancer and as an adjuvant therapy. J. Pineal Res. 41, 297-305.
218. Wu Y.H., Zhou J.N., Van Heerikhuize J., Jockers R. and Swaab D.F. (2007). Decreased MT1 melatonin receptor expression in the suprachiasmatic nucleus in aging and Alzheimer's disease. Neurobiol. Aging 28, 1239-1247.
219. Yakushiji T., Shirasaki T. and Akaike N. (1992). Non-competitive inhibition of GABAA responses by a new class of quinolones and non-steroidal anti-inflammatories in dissociated frog sensory neurones. Br. J. Pharmacol. 105, 13-18.
220. Yamazaki R., Kusunoki N., Matsuzaki T., Hashimoto S., and Kawai S. (2002). Nonsteroidal anti-inflammatory drugs induce apoptosis in association with activation of peroxisome proliferator-activated receptor gamma in rheumatoid synovial cells. J. Pharmacol. Exp. Ther. 302, 18-25.
221. Yenari M.A. (2002). Heat shock proteins and neuroprotection. Adv. Exp. Med. Biol. 513, 281-299.
222. Yermakova A.V. and O'Banion M.K. (2001). Downregulation of neuronal cyclooxygenase-2 expression in end stage Alzheimer's disease. Neurobiol. Aging. 22, 823-836.
223. Yin M.J., Yamamoto Y. and Gaynor R.B. (1998). The anti-inflammatory agents aspirin and salicylate inhibit the activity of I(kappa)B kinasebeta. Nature. 396, 77-80.