Topical β‐carotene is converted to retinyl esters in human skin ex vivo and mouse skin in vivo
Department of Dermatology, University Hospital, Geneva, Switzerland. Experimental Dermatology
(Impact Factor: 3.76).
10/2004; 13(9):558-61. DOI: 10.1111/j.0906-6705.2004.00194.x
Human epidermis contains endogenous retinoids (retinol and retinyl esters) and carotenoids (mostly beta-carotene). Previous studies have shown that the enzymes involved in retinoid metabolism are present in human epidermis. There is still a controversy about the presence in the skin of the enzymes able to convert beta-carotene into vitamin A (retinol), although a recent study demonstrated the conversion of beta-carotene into retinol in human cultured epidermal cells. In this study, we addressed the question of the possible bioconversion of topical beta-carotene into vitamin A or derivatives by human and mouse skin. Surgically excised human abdominal skin was mounted on Franz perfusion chambers to assess the cutaneous penetration of topical beta-carotene as well as its metabolism, after a 24-h incubation period, whereas hairless mice received topical beta-carotene 24 h before assaying epidermal beta-carotene and retinoid concentrations. Epidermal retinoid and beta-carotene concentrations were determined by high-pressure liquid chromatography. Topical beta-carotene penetrated well into human and mouse epidermis and induced a 10-fold (human) and a threefold (mouse) increase of epidermal retinyl esters, which demonstrates that topical beta-carotene is converted into retinyl esters by human and mouse epidermis and thus appears as a precursor of epidermal vitamin A.
Available from: Robert Landsiedel
- "Also, more specialized acyltransferases exist in human keratinocytes to assure the storage of the important skin retinol through esterification into retinyl esters. This step is catalyzed by two enzymes, acyl-CoA: retinol acyltransferase and lecithin: retinol acyltransferase ; their expression is modulated by the differentiation state of the keratinocytes (Antille et al. 2004; Törmä and Vahlquist 1990). "
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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.
Available from: Franz Oesch
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ABSTRACT: The mammalian skin has long been considered to be poor in drug metabolism. However, many reports clearly show that most drug metabolizing enzymes also occur in the mammalian skin albeit at relatively low specific activities. This review summarizes the current state of knowledge on drug metabolizing enzymes in the skin of human, rat, and pig, the latter, because it is often taken as a model for human skin on grounds of anatomical similarities. However only little is known about drug metabolizing enzymes in pig skin. Interestingly, some cytochromes P450 (CYP) have been observed in the rat skin which are not expressed in the rat liver, such as CYP 2B12 and CYP2D4. As far as investigated most drug metabolizing enzymes occur in the suprabasal (i.e. differentiating) layers of the epidermis, but the rat CYP1A1 rather in the basal layer and human UDP-glucuronosyltransferase rather in the stratum corneum. The pattern of drug metabolizing enzymes and their localization will impact not only the beneficial as well as detrimental properties of drugs for the skin but also dictate whether a drug reaches the blood flow unchanged or as activated or inactivated metabolite(s).
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ABSTRACT: Several carotenoids show enhancement of the immune response, inhibition of mutagenesis, reduction of induced nuclear damage, and protection from various neoplastic events in cells, tissues, and whole animals. Carotenoids also protect against photo-induced tissue damage. Some carotenoids, including β-carotene, quench highly reactive singlet oxygen under certain conditions and can block free radical-mediated reactions. There is a growing body of literature on the effects of β-carotene in human chronic diseases, including cancer. Evidence from observational epidemiological studies has shown that a high consumption of fruits and vegetables rich in carotenoids is associated with a low risk for cancer. However, some human intervention trials failed to demonstrate prevention of cancer by β-carotene supplements. Several studies have indicated that among subjects who neither smoked cigarettes nor drank alcohol, β-carotene was associated with a marked decrease in the risk of one or more recurrent adenomas but β-carotene supplementation conferred a modest increase in the risk of recurrence among those who smoked. An increase in the risk of lung cancer among smokers and asbestos workers who took β-carotene supplements is also reported. In fact this trial raises the possibility that these supplements may actually have harmful as well as beneficial effects. Alcohol intake and cigarette smoking appear to modify the effect of β-carotene supplementation on the risk of colorectal adenoma recurrence. Similarly, serum β-carotene levels have been associated with a decreased chance of developing cancer. This results show a remarkable consistency for the association of increased lung cancer risk with low amounts of dietary β-carotene or low plasma β-carotene concentrations. For stomach cancer, the evidence is also consistent, although the number of studies is more modest. For breast and prostate cancer, the studies indicate no consistent association of plasma or dietary β-carotene and reduced cancer risk. For colorectal cancer, the effect will be moderate, if existent. Whatever the results of these trials, carotenoids clearly show biological actions in animals distinct from their function as precursors of vitamin A. This review is an up-to-date and comprehensive analysis of pharmacological, toxicological reports and clinical applications of the β-carotene.
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