New Publication: A Study of Inter-Individual Variability in the Phase II Metabolism Xenobiotics in Human Skin

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Understanding skin metabolism is key to improve in vitro to in vivo extrapolations used to inform risk assessments of topically applied products. However, published literature is scarce and usually covers a limited and non-representative number of donors. We developed a protocol to handle and store ex vivo skin samples post-surgery and prepare skin S9 fractions to measure the metabolic activity of Phase II enzymes. The addition of an excess of cofactors immediately after preparation, before pre-incubation at 37°C for fifteen minutes before introducing the testing probe, greatly increased the stability of the enzymes. Using this standardised assay, the rates of sulphation (SULT) and glucuronidation (UGT) of 7-hydroxycoumarin, methylation (COMT) of dopamine and N-acetylation (NAT) of procainamide were measured in the ng/mg protein/h range in ninety individuals. Glutathione conjugation (GST) of 1-chloro-2,4-dinitrobenzene was assessed in a smaller pool of fifty donors. The metabolic rate was much faster and measured over six minutes using a different methodology to express rates in µg metabolite formed/mg protein/min. A comprehensive statistical analysis of these results was carried out, separating donors by age, gender and metabolic rate measured to estimate skin metabolism in the general population.

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