Biotransformation of 13(Z)-retinoic acid in mouse skin and human keratinocyte cultures.
The metabolism of 13-(CIS) in mouse skin in vivo which was treated with TPA (or vehicle) typically showed that the retinoid was oxidized to 4-hydroxy, 5,6-epoxy-13-CIS, 5,8-oxy-13-CIS and undergoes geometric isomerization to RA. Applied 13-(CIS) in human keratinocyte cultures showed that the retinoid was oxidized to 5,6-epoxy-13-CIS, 5,8-oxy-13-CIS, and isomers. Pretreatment with the antioxidant butylated hydroxyanisole(BHA) resulted in a large decrease in formation of the oxirane and increased formation of the alcohol in mouse skin. Proposed mechanisms suggested the involvement of peroxyl radicals and prostaglandin H synthase for the biotransformation of retinoids.
Chang
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HC
Division of Biochemical Toxicology, National Center for Toxicological Research, FDA, Jefferson, AR 72079, USA.
Samokyszyn
V M
VM
D000818:Animals; D001711:Biotransformation; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D015474:Isotretinoin / Q000493:pharmacokinetics*; D015603:Keratinocytes / Q000378:metabolism*; D051379:Mice; D012867:Skin / Q000378:metabolism*
D002083:Butylated Hydroxyanisole; D015474:Isotretinoin