The skin is the largest organ in the human body. As well as acting as a barrier to chemical, microbial and mechanical damage, it plays a vital role in a number of physiological functions such as thermoregulation, excretion, resorption, metabolism and sensory functions.
As with other organs in the body, the skin contains multiple enzymes, which are capable of metabolising endogenous and exogenous chemicals. Skin metabolism can, in turn, impact on other processes such as skin toxicity, skin absorption, homeostasis, drug delivery and efficacy. Because of the potential wide ranging effects of skin metabolism, interest is growing within a number of different industries including the cosmetics, chemical and pharmaceutical industries, and in vitro methods are now being established to understand the extent of metabolism in the skin, to elucidate the enzymes involved and to identify the metabolites formed.
At Cyprotex, our research has focused on evaluating the different in vitro methods for assessing skin metabolism, comparing skin metabolism with liver metabolism, and deciphering the metabolic routes. One of the main concerns regarding skin metabolism is the potential for bioactivation of pro-haptens to protein-reactive electrophilic species (reactive metabolites). This process has been identified as the initiating event in the Adverse Outcome Pathway for skin sensitisation. To understand the potential risk for skin sensitisation, Cyprotex offer a number of approaches such as DPRA, hCLAT, KeratinoSensTM and SenCeeTox®, the latter two incorporating in vitro systems that have been demonstrated to be metabolically active.
Dr Phil Butler, Head of ADME at our UK site, presented at the in-cosmetics® global conference in London in April 2017. His presentation covered skin physiology, the importance of skin metabolism in vital skin functions and our research in this field.