Oral cadmium exposure affects skin immune reactivity in rats

Dina Tucovic, Aleksandra Popov Aleksandrov, Ivana Mirkov, Marina Ninkov, Jelena Kulas, Lidija Zolotarevski, Vesna Vukojevic, Jelena Mutic, Nikola Tatalovic, Milena Kataranovski

Skin can acquire cadmium (Cd) by oral route, but there is paucity of data concerning cutaneous effects of this metal. Cd acquired by oral route can affect skin wound healing, but the effect of Cd on other activities involved in skin homeostasis, including skin immunity, are not explored. Using the rat model of 30-day oral administration of Cd (5 ppm and 50 ppm) in drinking water, basic aspects of immune-relevant activity of epidermal cells were examined. Dose-dependent Cd deposition in the the skin was observed (0.035 ± 0.02 µg/g and 0.127 ± 0.04 µg/g at 5 ppm and 50 ppm, respectively, compared to 0.012 ± 0.009 µg/g at 0 ppm of Cd). This resulted in skin inflammation (oxidative stress at both Cd doses and dose-dependent structural changes in the skin and the presence/activation of innate immunity cells). At low Cd dose inflammatory response (nitric oxide and IL-1β) was observed. Other inflammatory cytokines (IL-6 and TNF) response occurred at 50 ppm, which was increased further following skin sensitization with contact allergen dinitro-chlorobenzene (DNCB). Epidermal cells exposed to both Cd doses enhanced concanavalin A (ConA)-stimulated lymphocyte production of IL-17. This study showed for the first time the effect of the metal which gained access to the skin via gut on immune reactivity of epidermal cells. Presented data might be relevant for the link between dietary Cd and the risk of skin pathologies.