期刊
TOXICOLOGY AND APPLIED PHARMACOLOGY
卷 168, 期 3, 页码 189-199出版社
ACADEMIC PRESS INC
DOI: 10.1006/taap.2000.9025
关键词
cinnamic aldehyde; alcohol; acid; human; skin; metabolism; absorption; pyrazole; dehydrogenase; enzyme
trans-Cinnamaldehyde and trans-cinnamic alcohol have been commonly reported to cause allergic contact dermatitis (ACD) in humans. Cinnamaldehyde is a more potent skin sensitizer than cinnamic alcohol. It has been hypothesized that cinnamic alcohol is a prohapten that requires metabolic activation, presumably by oxidoreductase enzymes such as alcohol dehydrogenase (ADH) or cytochrome P450 2E1 (CYP2E1), to the protein-reactive cinnamaldehyde (a hapten). In this study, the in vitro percutaneous absorption and metabolism of cinnamaldehyde and cinnamic alcohol (78 mu mol dose) has been examined using freshly excised, metabolically viable, full-thickness breast and abdomen skin from six female donors. Penetration rates and total cumulative recoveries of cinnamic compounds that were present in receptor fluid, extracted from within the skin, evaporated from the skin surface, or remained unabsorbed on the skin surface after 24 h were quantified by reversed-phase high-performance liquid chromatography. Biotransformation of cinnamaldehyde to both cinnamic alcohol and cinnamic acid was observed. Topically applied cinnamic alcohol was converted to cinnamaldehyde (found on the skin surface only) and cinnamic acid. To establish whether these biotransformations were enzymatic, experiments were performed in the absence and presence of varying concentrations (80-320 mu mol) of the ADH/CYP2E1 inhibitors pyrazole: or 4-methylpyrazole. The observation that pyrazole significantly reduced (p < 0.05) the total penetration of cinnamic metabolites into receptor fluid, following either cinnamaldehyde or cinnamic alcohol treatment, but did not significantly affect parent chemical penetration, suggests that we are measuring cutaneous metabolic products of ADH activity. The skin absorption and metabolism of cinnamaldehyde and cinnamic alcohol will play an important role in the manifestation of ACD following topical exposure to these compounds. (C) 2000 Academic Press.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据