Kurohane Kohta, Sekiguchi Kota, Ogawa Erina, Tsutsumi Masato, Imai Yasuyuki
Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka.
Biol Pharm Bull. 2017 Nov 1;40(11):2010-2013. doi: 10.1248/bpb.b17-00557. Epub 2017 Aug 26.
Dibutyl phthalate (DBP) is a plasticizer used for many consumer products including cosmetics. Potential health concerns regarding DBP include reproductive and developmental toxicity, endocrine disruption and neurotoxicity. DBP is a high priority chemical as to reduction of exposure of children to it. Through reproductive toxicity studies, monobutyl phthalate (MBP) has been proposed to be the active metabolite derived from DBP. We previously demonstrated that DBP activates transient receptor potential ankyrin 1 (TRPA1) cation channels expressed on sensory neurons. We have also shown that DBP enhanced skin sensitization in a fluorescein isothiocyanate (FITC)-induced contact hypersensitivity (CHS) mouse model. Through MBP formation by esterase in the skin, it is possible that MBP exerts a major effect on the biological activity we observed. To test this possibility, we directly compared DBP and MBP. A more than 40-fold higher concentration of MBP as compared with DBP was required for activation of TRPA1 in vitro. Unlike DBP, MBP did not enhance skin sensitization to FITC. These results demonstrated that DBP directly, i.e., not through its metabolite MBP, activates TRPA1 and enhances FITC-CHS. It is noteworthy that butyl benzoate, a related compound, activated TRPA1 and enhanced FITC-CHS.
邻苯二甲酸二丁酯（DBP）是一种用于包括化妆品在内的许多消费品的增塑剂。关于DBP的潜在健康问题包括生殖和发育毒性、内分泌干扰和神经毒性。就减少儿童接触而言，DBP是一种高度优先关注的化学品。通过生殖毒性研究，有人提出单丁基邻苯二甲酸酯（MBP）是DBP衍生的活性代谢物。我们之前证明，DBP可激活感觉神经元上表达的瞬时受体电位锚蛋白1（TRPA1）阳离子通道。我们还表明，在异硫氰酸荧光素（FITC）诱导的接触性超敏反应（CHS）小鼠模型中，DBP增强了皮肤致敏作用。通过皮肤中的酯酶形成MBP，MBP有可能对我们观察到的生物活性产生主要影响。为了验证这种可能性，我们直接比较了DBP和MBP。在体外激活TRPA1时，所需MBP的浓度比DBP高40多倍。与DBP不同，MBP不会增强对FITC的皮肤致敏作用。这些结果表明DBP直接激活TRPA1并增强FITC-CHS，即不是通过其代谢物MBP。值得注意的是，相关化合物苯甲酸丁酯可激活TRPA1并增强FITC-CHS。
