Duell E A, Kang S, Voorhees J J
Department of Dermatology, University of Michigan Medical School, Ann Arbor 48109-0609, U.S.A.
J Invest Dermatol. 1997 Sep;109(3):301-5. doi: 10.1111/1523-1747.ep12335788.
The formation of all-trans retinoic acid is an oxidative process whereby retinol is converted to retinaldehyde and then to retinoic acid. Because retinol causes qualitative molecular changes similar to those produced by retinoic acid, we compared potency of retinol, retinaldehyde, and retinyl palmitate to retinoic acid and assessed the effects of occlusion. Retinoids were prepared in an experimental vehicle of 95% ethanol:propylene glycol (7:3) with anti-oxidant. Induction of retinoic acid 4-hydroxylase activity was the end point for comparison. Retinoic acid concentrations from 0.001% to 0.05% under occlusion produced a linear dose-response induction of 4-hydroxylase activity. The concentrations of the other retinoids under occlusion required to achieve significant induction of enzyme activity were 0.6% retinyl palmitate, 0.025% retinol, and 0.01% retinaldehyde. The linear dose-response was lost with retinoid concentrations in excess of 0.25% retinol or 0.5% retinaldehyde. Statistical analyses showed no difference in 4-hydroxylase activity between unoccluded and occluded retinol treated sites. By contrast, however, unoccluded sites treated with retinoic acid or retinyl palmitate had less induction of 4-hydroxylase activity than occluded sites. Retinol, retinaldehyde, and retinyl palmitate did not produce erythema but did increase epidermal thickness. Although retinol is a weaker retinoid than retinoic acid, the increased penetration of unoccluded retinol in comparison to unoccluded retinoic acid with this prototypic vehicle confers on retinol a more effective delivery of a retinoidal effect than unoccluded retinoic acid. Retinol at 0.25% may be a useful retinoid for application without occlusion because it does not irritate but does induce cellular and molecular changes similar to those observed with application of 0.025% retinoic acid.
全反式维甲酸的形成是一个氧化过程，在此过程中视黄醇先转化为视黄醛，然后再转化为维甲酸。由于视黄醇会引起与维甲酸产生的类似的定性分子变化，因此我们比较了视黄醇、视黄醛和棕榈酸视黄酯相对于维甲酸的效力，并评估了封闭的影响。类视黄醇制剂使用含抗氧化剂的95%乙醇：丙二醇（7:3）的实验载体。视黄酸4-羟化酶活性的诱导作为比较的终点。封闭条件下，浓度为0.001%至0.05%的维甲酸产生了4-羟化酶活性的线性剂量反应诱导。封闭条件下，其他类视黄醇达到显著诱导酶活性所需的浓度分别为0.6%棕榈酸视黄酯、0.025%视黄醇和0.01%视黄醛。当视黄醇浓度超过0.25%或视黄醛浓度超过0.5%时，线性剂量反应消失。统计分析表明，未封闭和封闭视黄醇处理部位的4-羟化酶活性没有差异。然而，相比之下，用维甲酸或棕榈酸视黄酯处理的未封闭部位的4-羟化酶活性诱导低于封闭部位。视黄醇、视黄醛和棕榈酸视黄酯不会产生红斑，但会增加表皮厚度。尽管视黄醇是一种比维甲酸弱的类视黄醇，但与使用这种原型载体的未封闭维甲酸相比，未封闭视黄醇的渗透性增加，使其比未封闭维甲酸更有效地传递类视黄醇效应。0.25%的视黄醇可能是一种无需封闭即可使用的有用类视黄醇，因为它不会引起刺激，但会诱导与使用0.025%维甲酸时观察到的类似的细胞和分子变化。
