Evaluation of skin phototoxicity of transdermally administered pharmaceuticals in Sprague-Dawley rats
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Laboratory Animal Research
RESEARCH
Open Access
Evaluation of skin phototoxicity of transdermally administered pharmaceuticals in Sprague-Dawley rats Nam Hee Youn1, Eun Ji Kim1, Jung-Sun Yi1, Joo Hwan Kim1, Ye-Jin Cho2, Ki Taek Nam2, Ki Sook Park1 and Jong Kwon Lee1*
Abstract Some drugs cause phototoxicity in humans when exposed to light, thus there is a need for an in vivo phototoxicity test to evaluate them. However, an in vivo phototoxicity test method to evaluate this has not been established. This study aimed to establish an in vivo phototoxicity test method for transdermally administered drugs. For this, we evaluated the phototoxicity using Sprague-Dawley (SD) rats for transdermal administered drugs and we studied the appropriate UVA dose using 8-methoxypsalen, which is a well-known phototoxic drug. We found that a UVA dose of 15 J/cm2 was dose and time dependent response compared to other UVA doses. We performed the Minimum Erythema Dose (MED) test because UVB can cause skin irritation by itself and selected 0.01 J/cm2 as an appropriate dose of UVB. Using the selected UVA and UVB doses, we performed a phototoxicity study of 6 pharmaceutical drugs, which included phototoxic and non-phototoxic drugs. As a result of the phototoxicity test, 100% accuracy was obtained when compared with previous studies. In addition, we performed histopathology to confirm the new findings. We found that histopathology can be used as an additional indicator of phototoxicity test for transdermally administered drugs. Keywords: Phototoxicity, In vivo test, Transdermal, Skin reaction, Histopathology
Introduction Sunlight is comprised of visible light, infrared light, and ultraviolet light, each with a different range of wavelengths. Ultraviolet light has a shorter wavelength than visible light, has high energy, and a strong chemical action. It can cause various phototoxic reactions, including acute reactions such as erythema on the skin, as well as chronic reactions such as photoaging. Phototoxicity is mainly induced by exposure of photoreactive chemicals to ultraviolet rays [1]. These compounds are chemically activated by ultraviolet rays and bind to DNA in the cell nucleus, or * Correspondence: [email protected] 1 Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju 28159, Republic of Korea Full list of author information is available at the end of the article
act on oxygen to form oxygen radicals or singlet oxygen molecules, which affect skin cells. Skin exposed to UV rays may exhibit symptoms such as erythema, eschar formation, edema, itchiness, stinging, and in severe cases, blistering or pigmentation may occur [1]. In addition, chemicals such as psoralen, quinolonebased antibiotics, anti-inflammatory drugs, and antidepressants among pharmaceuticals are reported to induce phototoxicity. Studies such as these are important in the evaluation and regulation of phototoxicity in pharmaceuticals [2–7]. The demand for evaluation of the p
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