Abstract
The exposure of the skin to medical drugs, skin care products, cosmetics, and other chemicals renders information on xenobiotic-metabolizing enzymes (XME) in the skin highly interesting. Since the use of freshly excised human skin for experimental investigations meets with ethical and practical limitations, information on XME in models comes in the focus including non-human mammalian species and in vitro skin models. This review attempts to summarize the information available in the open scientific literature on XME in the skin of human, rat, mouse, guinea pig, and pig as well as human primary skin cells, human cell lines, and reconstructed human skin models. The most salient outcome is that much more research on cutaneous XME is needed for solid metabolism-dependent efficacy and safety predictions, and the cutaneous metabolism comparisons have to be viewed with caution. Keeping this fully in mind at least with respect to some cutaneous XME, some models may tentatively be considered to approximate reasonable closeness to human skin. For dermal absorption and for skin irritation among many contributing XME, esterase activity is of special importance, which in pig skin, some human cell lines, and reconstructed skin models appears reasonably close to human skin. With respect to genotoxicity and sensitization, activating XME are not yet judgeable, but reactive metabolite-reducing XME in primary human keratinocytes and several reconstructed human skin models appear reasonably close to human skin. For a more detailed delineation and discussion of the severe limitations see the “Overview and Conclusions” section in the end of this review.
Highlights
Extrahepatic xenobiotic metabolism in organs of the body’s internal–external interfaces such as intestine, lung, and skin comes more and more into the center of interest in the field of xenobiotic metabolism studies (Gundert-Remy et al 2014)
Indicating that the net flux of caproyl-propranolol is dependent on its conversion to propranolol
Some other oxidoreductases essentially involved in the metabolism of endogenous compounds such as steroid 5α-reductase and 7-dehydrocholesterol A7-reductase occasionally become important for xenobiotic metabolism when xenobiotics are in partial structures sufficiently similar to their endogenous substrates
Summary
Extrahepatic xenobiotic metabolism in organs of the body’s internal–external interfaces such as intestine, lung, and skin comes more and more into the center of interest in the field of xenobiotic metabolism studies (Gundert-Remy et al 2014). In 2007, we published a review on xenobiotic-metabolizing enzymes (XME) in the skin of man, rat, and pig (Oesch et al 2007). In order not to force the reader to go back to our 2007 review (Oesch et al 2007), we include in short and succinctly the data on XME in the skin of man, rat, and pig published prior to 2007. The main purpose of the numerical values given in this review was to show that numerically measurable activities were reported and may, with due caution, be considered as high, moderate, or low. Expression of CYP1A1 and CYP2C11 was higher in the skin than in the liver
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