Abstract
Chromium hypersensitivity (chromium-induced allergic contact dermatitis) is an important issue in occupational skin disease. Hexavalent chromium (Cr (VI)) can activate the Akt, Nuclear factor κB (NF-κB), and Mitogen-activated protein kinase (MAPK) pathways and induce cell death, via the effects of reactive oxygen species (ROS). Recently, cell death stimuli have been proposed to regulate the release of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1). However, the exact effects of ROS on the signaling molecules and cytotoxicity involved in Cr(VI)-induced hypersensitivity have not yet been fully demonstrated. N-acetylcysteine (NAC) could increase glutathione levels in the skin and act as an antioxidant. In this study, we investigated the effects of NAC on attenuating the Cr(VI)-triggered ROS signaling in both normal keratinocyte cells (HaCaT cells) and a guinea pig (GP) model. The results showed the induction of apoptosis, autophagy and ROS were observed after different concentrations of Cr(VI) treatment. HaCaT cells pretreated with NAC exhibited a decrease in apoptosis and autophagy, which could affect cell viability. In addition, Cr (VI) activated the Akt, NF-κB and MAPK pathways thereby increasing IL-1α and TNF-α production. However, all of these stimulation phenomena could be inhibited by NAC in both of in vitro and in vivo studies. These novel findings indicate that NAC may prevent the development of chromium hypersensitivity by inhibiting of ROS-induced cell death and cytokine expression.
Highlights
Chromium is ubiquitous in the environment and can be found in pigments, chrome-plated metals, tanned shoe leather, cement, detergents, and industrial chromium waste dumps [1]
NAC attenuated Cr(VI)-induced apoptotic cell death To investigate the effects of NAC on Cr(VI)-induced apoptotic cell death, the level of early apoptosis was analyzed by flow cytometry with the Annexin V apoptosis detection kit
The barrier integrity and innate immune responses in the epidermis are important for the maintenance of skin immune homeostasis and pathogenesis of inflammatory skin diseases [48]
Summary
Chromium is ubiquitous in the environment and can be found in pigments, chrome-plated metals, tanned shoe leather, cement, detergents, and industrial chromium waste dumps [1]. ROS play an important role in the pathogenesis of allergic contact dermatitis (ACD) [5,6]. Metallic allergens such as nickel and chromium are both producers of ROS and have been proved to induce ACD [7,8]. Chromium, cobalt and other metals produce reactive radicals to result in toxic effects but this is not true for lead. Chromium hypersensitivity is common in both the general population and certain occupation-related workers, with prevalences of approximately 0.5% and 4–5% in European populations and cement workers, respectively [11,12]. Chromium hypersensitivity is an important occupational skin disease among cement workers
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