Abstract
Melatonin (MLT), N-acetyl-5-methoxytryptamine, is mainly secreted by the pineal gland. The ultraviolet (UV), infrared (IR) and1H-NMR spectra of irradiated and non-irradiated MLT were measured, and phototoxicity tests of MLT, anthracene (positive control) and sodium lauryl sulfate (SLS, negative control) were performed. The methods employed include bothin vitro tests such as MTS assay using the human fibroblast cell and yeast growth inhibition assay usingCandida albicans andin vivo method using the skin of guinea pig. UV absorption spectra and1H-NMR spectra of MLT were changed by UVA (365 nm, 15 J/cm2), but IR spectra of MLT were not changed. The fifty percent inhibitory concentration (IC50) ratio (UV-/UV+) of MLT was 10. The inhibition zone of irradiated-paper disks treated with MLT was not observed. According to the results of histopathological examination, no pathologic lesion was observed in the non-irradiated group, but slight degeneration of keratinocytes in the epidermis, hemorrhage and vasodilation in dermis were observed in the irradiated group. These results indicate that the molecular structure of MLT is altered by UVA to unidentified photoproducts and a moderate phototoxicity of MLT is predicted.
Similar content being viewed by others
References Cited
Axelrod J., Franschini, F. and Velo, G. P. (eds.)., The pineal gland and its neuroendocrine role, Proc. NATO Adv. Study, Erice, Italy, Plenum Press, New York, 1982.
Babu, V. and Joshi, P. C., Tryptophan as an endogenous photosensitizer to elicit harmful effects of ultraviolet B.Indian J. Biochem. Biophys., 29(3), 296–298 (1992).
Bangha, E., Elsner, P. and Kistler, G. S., Suppression of UV-induced erythema by topical treatment with melatonin.Dermatology, 195, 248–252 (1997).
Bangha, E., Elsner, P. and Kistler, G. S., Suppression of UV-induced erythema by topical treatment with melatonin. A dose response study.Dermatology, 288, 522–526 (1996).
Cronin. F., Contact dermatitis. Churchill Livingstone, Edinburgh, pp. 414, 1980.
Gabriel, K. L., Forbes, P. D. and Davies, R. E., Phototoxicity.J. Toxicol-Cut and Ocular Toxicol., 4, 185–191 (1985).
Goodwin, C. J., Holt, S. J., Dowens, S. and Marshall, N. J., Microculture tetrazolium assay: a comparison between two new tetrazolium salts, XTT and MTS.J. Immunol. Methods, 179, 95–103 (1995).
Kochevar, I. E., Phototoxicity of nonsteroidal inflammatory drugs.Arch. Dermatol., 125, 824–826 (1989).
Kramer, H. E. and Maute, A., Sensitized photooxygenation according to type I mechanism (radical mechanism).Photochem. Photobiol., 15, 7–42 (1972).
Lee, B. J., Parrott, K. A., Ayres, J. W. and Sack, R. L., Preliminary evaluation of transdermal delivery of melatonin in human subjects.Res Commun Mol Pathol Pharmacol., 85, 337–346 (1994).
Lichfield, J. P. and Wilcoxon, F. A., Simplified method of evaluating dose-effect experiments.J. Pharmacol. Exp. Ther., 96, 95–115 (1949).
Ljunggren, B. and Bjellerup, M., Systemic drug phototoxicity.Photodermatology, 3, 26–35 (1986).
Lora, M. G., Jeanne, L. R. and Carl, F. W., Rapid colorometric assay for cell viability: Application to the quantitation of cytotoxic and growth inhibitory lymphokines.J. Immuno. Med., 70, 257–268 (1984).
Marzulli, F. N. and Maibach, H. I., Phototoxicity (photoirritation) of topical and systemic agents.Dermatoxicology, 431–440 (1987).
Maurner, T., Phototoxicity testing —in vivo andin vitro. Fd. Chem. Toxicol., 25, 404–414 (1987).
Morikawa, F., Nakayama, Y., Fukuda, M., Hammano, M. and Toda, K., Techniques for evaluation of phototoxicity and photoallergy in laboratory animals and man. in sunlight and man. Edited by MA Pathak, LC Harber, M Seiji and A Kikuta: consulting editor. Fitzpatrick T.B., University of Tokyo Press, Tokyo, pp. 529–557, 1974.
Nilsson, R., Maurer, T. and Remond, N., A standard protocol for phototoxicity testing; results from an interlaboratory study.Contact Dermatitis, 28, 285–290 (1993).
Nilsson, R., Merkel, P. and Kearns, D., Unambiguous Evidence for participating of singlet oxygen in photodynamic oxidation of amino acids.Photochem. Photobiol., 16, 117–124 (1972).
Nilsson, R., Swanbeck, G. and Wennersten, G., Primary mechanism of erythrocyte photolysis induced by biological sensitizers and phototoxic drugs.Photochem. Photobiol., 22, 183–186 (1975).
Peak, M. J., Peak, J. G., Moehring, M. P. and Webb, R. B., Ultraviolet action spectra for DNA dimmer induction, lethality, and mutagenesis in E-Coli with emphasis on the UVB region.Photochem. Photobiol., 40, 613–620 (1984).
Poerggeler, B., Saarela, S., Reiter, R. J., Tam, D. X., Chen, L. D., Manchester, L. C. and Barlow-Walden, L. R., Melatonin-A highly potent endogenous radical scavenger and electron donor: new aspects of the oxidation chemistry of this indole accessedin vitro.Ana Ny Acad. Sci., 738, 419–420 (1994).
Reiter, R. J., Pineal melatonin; Cellbiology of its synthesis and of its physiological interactions.Endocr. Rev., 12, 151–180 (1991).
Ssavedra, J. M., Brownstein, M. and Axelrod, J., Circadian rhythm of pineal serotonin N-acetyl-transferase activity.J. Pharmacol. Exp. Ther., 186, 508–519 (1973).
Staberg, B., Walf, H. C., Poulsen, T., Klemp, P. and Brodthagen, H., Carcinogenic effect of sequential artificial sunlight and UVA irradiation in hairless mice.Arch. Dermatol., 119, 641–643 (1983).
Sugiyama, M., Itagaki, H. and Keto, S., Assay to predict phototoxicity of chemicals: (II) yeast growth inhibition assay and battery system with photohemolysis assay.AATEX, 2, 193–202 (1994).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kim, YO., Chung, H.J., Chung, ST. et al. Phototoxicity of melatonin. Arch Pharm Res 22, 143–150 (1999). https://doi.org/10.1007/BF02976538
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02976538