N-acetylcysteine attenuates hexavalent chromium-induced hypersensitivity through inhibition of cell death, ROS-related signaling and cytokine expression

• Published in: PloS one Vol. 9; no. 9; p. e108317
• Main Authors: Lee, Yu-Hsuan, Su, Shih-Bin, Huang, Chien-Cheng, Sheu, Hamm-Ming, Tsai, Jui-Chen, Lin, Chia-Ho, Wang, Ying-Jan, Wang, Bour-Jr
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23.09.2014; Public Library of Science (PLoS)
• Subjects: Acetylcysteine; Acetylcysteine - pharmacology; Acetylcysteine - therapeutic use; AKT protein; Allergy; Animals; Antioxidants; Antioxidants - pharmacology; Antioxidants - therapeutic use; Apoptosis; Apoptosis - drug effects; Autophagy; Autophagy - drug effects; Biochemistry; Biocompatibility; Biology and Life Sciences; Cancer; Cell death; Cells, Cultured; Chromium; Chromium - toxicity; Contact dermatitis; Cytokines; Cytotoxicity; Dermatitis; Dermatitis, Allergic Contact - drug therapy; Dermatitis, Allergic Contact - etiology; Dermatitis, Allergic Contact - pathology; Dermatitis, Allergic Contact - prevention & control; Drug Evaluation, Preclinical; Female; Gene expression; Gene Expression Regulation - drug effects; Glutathione; Guinea Pigs; Hexavalent chromium; Hypersensitivity; In vivo methods and tests; Inflammation; Inhibition; Interleukin; Interleukin 1; Interleukin-1alpha - biosynthesis; Interleukin-1alpha - genetics; Keratinocytes - drug effects; Keratinocytes - metabolism; Kinases; MAP kinase; MAP Kinase Signaling System - drug effects; Medicine and Health Sciences; Mitochondria; Mortality; NF-kappa B - physiology; NF-κB protein; Occupational diseases; Occupational health; Oncogene Protein v-akt - physiology; Oxygen; Pathogenesis; Pathways; Phagocytosis; Pharmacy; Protein kinase; Proteins; Reactive oxygen species; Reactive Oxygen Species - antagonists & inhibitors; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Science; Signal transduction; Signal Transduction - drug effects; Signaling; Skin; Skin diseases; Toxicity; Transcription factors; Tumor necrosis factor; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - genetics; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0108317

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.