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Safety Evaluation and Anti-wrinkle Effects of Retinoids on Skin

  • Published : 2010.03.04

Abstract

Retinoids have many beneficial effects on dermatological applications. But, retinoids cause skin irritation. In this study, the safety of retinoids was clarified via both primary skin irritation test in rabbits and sensitization study using an integrated model for the differentiation of chemical-induced allergic and irritant skin reaction (IMDS), an alternative method to sensitization test. The effects of retinoids on the change of ultraviolet A (UVA)-induced matrix metalloproteinase-1 (MMP-1) in human skin fibroblasts and the modulation of type-1 pN collagen synthesis in hairless mice were examined to clarify the anti-wrinkle effects. Alltrans retinol (t-ROL) and its derivative, all-trans retinoic acid (t-RA), showed mild skin irritation but did not induce the sensitization. t-ROL and t-RA exerted anti-wrinkle effects by inhibiting the UVA-induced MMP-1 in human skin fibroblasts and increasing the type-1 pN collagen synthesis in hairless mice. These findings suggest that retinoids do not induce the allergy, and show anti-wrinkle effects by decreasing MMP-1 activation and increasing collagen synthesis.

Keywords

References

  1. Arts, J.H.E., Droge, S.C.M., Bloksma, N. and Kuper, C.F. (1996). Local lymph node activation in rats after dermal application of the sensitizers 2,4-dinitrochlorobenzene and trimellitic anhydride. Food Chem. Toxicol., 34, 55-62. https://doi.org/10.1016/0278-6915(95)00089-5
  2. Basketter, D.A. and Gerberick, G.F. (1996). An interlaboratory evaluation of the Buehler test for the identification and classification of skin sensitizers. Contact Dermatitis, 35, 146-151. https://doi.org/10.1111/j.1600-0536.1996.tb02332.x
  3. Blotz, A., Michel, L., Moysan, A., Blumel, J., Dubertret, L., Ahr, H.J. and Vohr, H.W. (2000). Analyses of cutaneous floroquinolones photoreactivity using the integrated model for the differentiation of skin reactions. J. Photochem. Photobiol. B: Biol., 58, 46-53. https://doi.org/10.1016/S1011-1344(00)00097-X
  4. Chamberlain, M. and Basketter, D.A. (1996). The local lymph node assay: status of validation. Food Chem. Toxicol., 34, 999-1002. https://doi.org/10.1016/S0278-6915(96)00058-0
  5. Chen, S., Kiss, I. and Tramposch, K.M. (1992). Effect of all-trans retinoic acid on UVB-irradiated and non-irradiated hairless mouse skin. J. Invest. Dermatol., 98, 248-254. https://doi.org/10.1111/1523-1747.ep12556066
  6. Clark, S.D., Kobayashi, D.K. and Welgus, H.G. (1987). Regulation of the expression of tissue inhibitor of metalloproteinases and collagenase by retinoids and glucocorticoids in human fibroblasts. J. Clin. Invest., 80, 1280-1288. https://doi.org/10.1172/JCI113203
  7. Draize, J.H. (1959). Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics - Dermal Toxicity. pp. 46-59. Association of Food and Drug Officials of the United States, Washington DC.
  8. Fluhr, J.W., Vienne, M.P., Lauze, C., Dupuy, P., Gehring, W. and Gloor, M. (1999). Tolerance profile of retinol, retinaldehyde and retinoic acid under maximized and long-term clinical conditions. Dermatology Suppl., 1, 57-60.
  9. Gamer, A.O., Nies, E. and Vohr, H.W. (2008). Local lymph node assay (LLNA): Comparison of different protocols by testing skin-sensitizing epoxy resin system components. Regul. Toxicol. Pharmacol., 52, 290-298. https://doi.org/10.1016/j.yrtph.2008.08.018
  10. Gerberick, G.F., Cruse, L.W. and Ryan, C.A. (1999). Local lymph lode assay: differentiating allergic and irritant responses using flow cytometry. Methods, 19, 48-55. https://doi.org/10.1006/meth.1999.0826
  11. Gerberick, G.F., Ryan, C.A., Dearman, R.J. and Kimber, I. (2007). Local lymph node assay (LLNA) for detection of sensitization capacity of chemicals. Methods, 41, 54-60. https://doi.org/10.1016/j.ymeth.2006.07.006
  12. Griffiths, C.E.M., Russman, A.N., Majmudar, G., Singer, R.S., Hamilton, T.A. and Voorhees, J.J. (1993). Restoration of collagen formation in photodamaged human skin by tretinoin (retinoic acid). New Engl. J. Med., 329, 530-535. https://doi.org/10.1056/NEJM199308193290803
  13. Hariya, T., Hatao, M. and Ichikawa, H. (1999). Development of a non-radioactive endpoint in a modified local lymph node assay. Food Chem. Toxicol., 37, 87-93. https://doi.org/10.1016/S0278-6915(98)00102-1
  14. Homey, B., Schilling, C.V., Blumel, J., Schuppe, H.C., Ruzicka, T., Ahr, H.J., Lehmann, P. and Vohr, H.W. (1998). An integrated model for the differentiation of chemical-induced allergic and irritant skin reactions. Toxicol. Appl. Pharmacol., 153, 83-94. https://doi.org/10.1006/taap.1998.8535
  15. Jung, K.M., Bae, I.H., Kim, B.H., Kim, W.K., Chung, J.H., Park, Y.H. and Lim, K.M. (2010). Comparison of flow cytometry and immunohistochemistry in non-radioisotopic murine lymph node assay using bromodeoxyuridine. Toxicol. Lett., 192, 229-237. https://doi.org/10.1016/j.toxlet.2009.10.024
  16. Kashima, R., Oyake, Y., Okada, J. and Ikeda, Y. (1996). Improved ex vivo/in vitro lymph node cell proliferation assay guinea pigs for a screening test of contact hypersensitivity of chemical compounds. Toxicology, 114, 47-55. https://doi.org/10.1016/S0300-483X(96)89846-5
  17. Kim, M.S., Kim, Y.K., Cho, K.H. and Chung, J.H. (2006). Regulation of type I procollagen and MMP-1 expression after single or repeated exposure to infrared radiation in human skin. Mech. Ageing Dev., 127, 875-882. https://doi.org/10.1016/j.mad.2006.09.007
  18. Kim, B.H., Lee, Y.S. and Kang, K.S. (2003). The mechanism of retinol-induced irritation and its application to anti-irritant development. Toxicol. Lett., 146, 65-73. https://doi.org/10.1016/j.toxlet.2003.09.001
  19. Kimber, I. (2001). The local lymph node assay and potential application to the identification of drug allergens. Toxicology, 158, 59-64. https://doi.org/10.1016/S0300-483X(00)00408-X
  20. Kimber, I., Dearman, R.J., Scholes, E.W. and Basketter, D.A. (1999). The local lymph node assay: developments and application. Toxicology, 93, 13-31.
  21. Kligman, L.H., Sapadin, A.N. and Schwartz, E. (1996). Peeling agents and irritants, unlike tretinoin, do not stimulate collagen synthesis in the photoaged hairless mouse. Arch. Dermatol. Res., 288, 615-620. https://doi.org/10.1007/BF02505265
  22. Loveless, S.E., Ladics, G.S., Gerberick, G.F., Ryan, C.A., Basketter, D.A., Scholes, E.W., House, R.V., Hilton, J., Dearman, R.J. and Kimber, I. (1996). Further evaluation of the local lymph node assay in the final phase of an international collaborative trial. Toxicology, 108, 141-152. https://doi.org/10.1016/0300-483X(95)03279-O
  23. Manetz, T.S. and Meade, B.J. (1999). Development of a flow cytometry assay for the identification and differentiation of chemicals with the potential to elicit irritation, IgE-mediated, or T cell-mediated hypersensitivity responses. Toxicol. Sci., 48, 206-217. https://doi.org/10.1093/toxsci/48.2.206
  24. Maurer, T., Weirich, E.G. and Hess, R. (1980). The optimization test in guinea pig in relation to other predictive sensitization methods. Toxicology, 15, 163-171. https://doi.org/10.1016/0300-483X(80)90050-5
  25. Mitani, H., Koshiishi, I., Sumita, T. and Imanari, T. (2001). Prevention of the photodamage in the hairless mouse dorsal skin by kojic acid as an iron chelator. Eur. J. Pharmacol., 411, 169-174. https://doi.org/10.1016/S0014-2999(00)00873-6
  26. Pan, L., Eckhoff, C. and Brinckerhoff, C.E. (1995). Suppression of collagenase gene expression by all-trans and 9-cis retinoic acid is ligand dependent and requires both RARs and RXRs. J. Cell Biochem., 57, 575-589. https://doi.org/10.1002/jcb.240570402
  27. Pichowski, J.S., Cumberbatch, M., Dearman, R.J., Basketter, D.A. and Kimber, I. (2000). Investigation of induced changes in interleukin 1$\beta$ mRNA expression by cultured human dendritic cells as an in vitro approach to skin sensitization testing. Toxicol. In vitro, 14, 351-360. https://doi.org/10.1016/S0887-2333(00)00030-8
  28. Sakabe, T., Tsuchiya, H., Endo, M., Tomita, A., Ishii, K., Gonda, K., Murai, R., Takubo, K., Hoshikawa, Y., Kurimasa, A., Ishibashi, N., Yanagida, S. and Shiota, G. (2007). An antioxidant effect by acyclic retinoid suppresses liver tumor in mice. Biochem. Pharmacol., 73, 1405-1411 https://doi.org/10.1016/j.bcp.2006.12.030
  29. Schwartz, E., Cruickshank, F.A., Mezick, J.A. and Kligman, L.H. (1991). Topical all-trans retinoic aicd stimulates collagen synthesis in vivo. J. Invest. Dermatol., 96, 975-978. https://doi.org/10.1111/1523-1747.ep12476385
  30. Sikorski, E.E., Gerberick, G.F., Ryan, C.A., Miller, C.M. and Ridder, G.M. (1996). Phenotypic analysis of lymphocyte subpopulations in lymph nodes draining the ear following exposure to contact allergens and irritants. Fundam. Appl. Toxicol., 34, 25-35. https://doi.org/10.1006/faat.1996.0172
  31. Ulrich, P., Homey, B. and Vohr, H.W. (1998). A modified murine local lymph node assay for the differentiation of contact photoallergy from phototoxicity by analysis of cytokine expression in skin-draining lymph node cells. Toxicology, 125, 149-168. https://doi.org/10.1016/S0300-483X(97)00156-X
  32. Vohr, H.W., Blümel, J., Blotz, A., Homey, B. and Ahr, H.J. (2000). An intra-laboratory validation of the integrated model for the differentiation of skin reactions (IMDS): discrimination between (photo) allergic and (photo) irritant skin reactions in mice. Arch. Toxicol., 73, 501-509. https://doi.org/10.1007/s002040050001
  33. Vohr, H.W., Homey, B., Schuppe, H.C. and Kind, P. (1994). Detection of photoreactiveity demonstrated in a modified local lymph node assay in mice. Photodermatol. Photoimmunol. Photomed., 10, 57-64.
  34. Wang, L., Tankersley, L.R., Tang, M., Potter, J.J. and Mezey, E. (2002). Regulation of the murine $\alpha$2(I) collagen promoter by retinoic acid and retinoid X receptors. Arch. of Biochem. and Biophys., 401, 262-270. https://doi.org/10.1016/S0003-9861(02)00058-9
  35. Wright, J.K., Clark, I.M., Cawston, T.E. and Hazleman, B.L. (1991). The secretion of the tissue inhibitor of metalloproteinase (TIMP) by human synovial fibroblasts is modulated by alltrans retinoic acid. Biochem. Biophys. Acta, 1133, 25-30. https://doi.org/10.1016/0167-4889(91)90237-R
  36. Yoshioka, H., Oyamada, I. and Usuku, G. (1987). An assay of collagenase activity using enzyme-linked immunosorbent assay for mammalian collagenase. Anal. Biochem., 166, 172-177. https://doi.org/10.1016/0003-2697(87)90559-8

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