Gunning Desiree B, Barua Arun B, Myers Ronald K, Ueltschy Amanda, Romans David, Olson James A
Departments of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, Iowa 50011, USA.
Skin Pharmacol Appl Skin Physiol. 2002 Jul-Aug;15(4):205-12. doi: 10.1159/000065966.
The efficacy of all-trans-retinoic acid (tRA) and all-trans-retinoyl beta-glucuronide (RAG), a water-soluble metabolite of vitamin A, in the topical treatment of acne is comparable. However, whereas 3.3 mM tRA shows side effects, 3.3 mM RAG does not. To assess the relative toxic and histologic effects (dermal and epidermal changes) of long-term (24-week) daily applications of tRA and RAG on the skin, separate skin patches were measured and marked dorsally on the skin of six 21-day-old, castrated male pigs. Each skin patch area was treated daily with a cream formulation containing either 3.3 mM RAG, 16.5 mM RAG, 33 mM RAG, 3.3 mM tRA, 16.5 mM tRA or blank cream. To serve as controls, one patch received no treatment, one patch received blank cream only and for 5.3 weeks one 'washed' patch was given daily application of 33 mM RAG with routine cleansing using a mild soap typical of skin care. The amount of cream used per square centimeter remained the same during the course of the study. Biopsy tissue was collected at -1, 0, 2, 4, 8, 12 and 24 weeks from 7 test patches. The 'washed' patch was biopsied once at the 5.3-week mark. Topically applied RAG cream (3.3 mM) resulted in significantly lower histologic scores when compared with scores from tissue treated with an equimolar concentration of tRA. The highest concentration of RAG tested (33.3 mM) resulted in a response comparable to that observed in the lowest tRA (3.3 mM) treated patch area. Daily cleansing of the test area receiving 33.3 mM RAG completely eliminated any clinical signs or negative histologic changes. In conclusion, long-term topical tRA treatment in young pigs, as in humans, showed dose-dependent adverse effects on the skin, whereas RAG treatment had significantly lower histologic changes and less irritation and/or inflammation.
全反式维甲酸（tRA）和全反式视黄酰β-葡萄糖醛酸酯（RAG，维生素A的一种水溶性代谢产物）在痤疮局部治疗中的疗效相当。然而，3.3 mM的tRA会产生副作用，而3.3 mM的RAG则不会。为评估长期（24周）每日局部应用tRA和RAG对皮肤的相对毒性和组织学影响（皮肤和表皮变化），在6头21日龄去势雄性猪的背部皮肤上测量并标记了不同的皮肤贴片区域。每个皮肤贴片区域每天用含有3.3 mM RAG、16.5 mM RAG、33 mM RAG、3.3 mM tRA、16.5 mM tRA的乳膏制剂或空白乳膏进行治疗。作为对照，一个贴片不进行治疗，一个贴片仅使用空白乳膏，并且在5.3周内，一个“清洗”贴片每天使用33 mM RAG并使用典型的温和皮肤护理肥皂进行常规清洁。在研究过程中，每平方厘米使用的乳膏量保持不变。在第-1、0、2、4、8、12和24周从7个测试贴片中采集活检组织。“清洗”贴片在5.3周时进行一次活检。与用等摩尔浓度tRA处理的组织得分相比，局部应用RAG乳膏（3.3 mM）导致的组织学得分显著更低。测试的最高浓度RAG（33.3 mM）产生的反应与在最低浓度tRA（3.3 mM）处理的贴片区域中观察到的反应相当。对接受33.3 mM RAG的测试区域进行每日清洁完全消除了任何临床体征或负面组织学变化。总之，与人类一样，幼猪长期局部应用tRA治疗对皮肤显示出剂量依赖性不良反应，而RAG治疗的组织学变化显著更低，刺激和/或炎症更少。
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