Skin permeation of nickel, cobalt and chromium salts in ex vivo human skin, visualized using mass spectrometry imaging

Lina Hagvall,Masoumeh Dowlatshahi Pour,Jiabao Feng,Moshtak Karma,Yolanda Hedberg,Per Malmberg

doi:10.1016/j.tiv.2021.105232

Lina Hagvall, Masoumeh Dowlatshahi Pour + Show 4 more

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https://doi.org/10.1016/j.tiv.2021.105232

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Skin permeation and distribution of three of the most common skin sensitizers was investigated using a previously developed animal-free exposure method combined with imaging mass spectrometry. Nickel, cobalt, and chromium (III) salts were dissolved in a buffer and exposed to human skin ex vivo, to be analyzed using time of flight secondary ion mass spectrometry (ToF-SIMS). Our findings demonstrate that metal haptens mainly accumulated in the stratum corneum, however all three metal sensitizers could also be detected in the epidermis. Cobalt and chromium (III) species penetrated into the epidermis to a larger extent than nickel species. The degree of penetration into the epidermis is suggested to be affected by the sensitization potency of the metal salts, as well as their speciation, i.e. the amount of the respective metal present in the solution as bioaccessible and solubilised ions. Our method provided permeation profiles in human skin for known sensitizers, on a level of detail that is not possible to achieve by other means. The findings show that the permeation profiles are different, despite these sensitizers being all metal ions and common causes of contact allergy. Studying skin uptake by only considering penetration through the skin might therefore not give accurate results.

Highlights

Allergic contact dermatitis is the symptom of T-cell mediated sensi tization, i.e., contact allergy
In order to initiate such a sensitization, it is believed that skin sensitizers first need to penetrate the skin barrier through the stratum corneum, reaching into the epidermis where they bind to skin proteins or other macro molecules forming antigens distinguishable to dendritic cells(Karlberg et al, 2008)
The aim of the present study was to map the distribution in human skin ex vivo after exposure to nickel, cobalt and chromium (III) salts using imaging mass spectrometry

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Introduction

Allergic contact dermatitis is the symptom of T-cell mediated sensi tization, i.e., contact allergy. In the case of metals, metal ions constitute the active hapten and skin contact with everyday metal objects releasing sensitizing metal ions, such as nickel or cobalt ions, can cause allergic contact dermatitis in sensitized individuals(Thyssen et al, 2013). It is of great interest to study metal ion penetration, distribution, and interaction within the different layers of the skin. This has so far mostly been studied using quantitative methods with practical limitations such as tape stripping or receptor fluid analysis of diffusion cell experiments

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