Abstract:

Zhang Mengli, Wei Jun, Ma Pengcheng, Li Lingjun, Qian Kun, Tao Lei Department of Cosmetic Laser Surgery, Hospital of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China （Zhang ML）; Department of Pharmacal Research, Hospital of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China （Wei J, Ma PC, Li LJ, Qian K, Tao L） Corresponding author: Ma Pengcheng, Email: mpc815@163.com 【Abstract】 Objective To estimate the effect of a tretinoin derivative ECPIRM on retinoic acid receptors （RARs）, and to observe skin irritation responses to it in mice. Methods Cultured SCL-1 cells were divided into 2 groups to be treated with culture medium containing 10 μmol/L ECPIRM （ECPIRM group） or 10 μmol/L all-trans retinoic acid （ATRA） （ATRA group） for 24 hours, and those treated with drug-free culture medium served as the control group. Western blot analysis and real-time fluorescence-based quantitative PCR were performed to quantify the protein and mRNA s of RARs （RARα, RARβ, RARγ and RXRα） respectively. In addition, real-time fluorescence-based quantitative PCR was conducted to measure the mRNA s of two target genes of the activated RAR signaling pathway, i.e., cytochrome P450 26A1 （CYP26A1） and tazarotene-induced gene 1 （TIG1）. Eight BALB/c mice were equally divided into 2 groups to be topically treated with 0.075% ECPIRM gel or 0.05% ATRA cream at equal molar concentrations on the shaved skin once daily for 21 successive days. Skin irritation reactions were assessed in these mice. Results Compared with the control group, the ATRA group showed significantly increased protein and mRNA s of RARα, RARβ and RARγ （all P < 0.05）. The mRNA s of CYP26A1 and TIG1 genes in the ATRA group were 25.49 and 3.88 times that in the control group respectively （both P < 0.01）. However, there was no significant difference in the protein s of RARα, RARβ, RARγ and RXRα, or mRNA s of RARα, RARβ, RARγ, CYP26A1 and TIG1 between the ECPIRM group and control group （all P > 0.05）. Obvious Skin irritation reactions such as erythema and desquamation were observed in BALB/c mice after 2-day topical treatment with ATRA cream, and their degree peaked after 5-day treatment. However, neither erythema nor desquamation was observed in BALB/c mice during 21-day treatment with 0.075% ECPIRM gel. Conclusion Unlike ATRA, ECPIRM cannot activate the canonical RAR signaling pathway or cause skin irritation reactions.