title: N-acetylcysteine attenuates hexavalent chromium-induced hypersensitivity through inhibition of cell death, ROS-related signaling and cytokine expression.
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.
authors.affiliation: Department of Environmental and Occupational Health, National Cheng Kung University Medical College, Tainan, Taiwan.
authors.forename: Yu-Hsuan
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Department of Occupational Medicine, Chi-Mei Medical Center, Tainan, Taiwan; Department of Leisure, Recreation and Tourism Management, Southern Taiwan University of Science and Technology, Tainan, Taiwan; Department of Medical Research, Chi Mei Medical Center, Liouying, Tainan, Taiwan.
authors.forename: Shih-Bin
authors.initials: SB
authors.lastname: Su
authors.affiliation: Department of Emergency Medicine, Chi-Mei Medical Center, Tainan, Taiwan; Department of Child Care and Education, Southern Taiwan University of Science and Technology, Tainan, Taiwan.
authors.forename: Chien-Cheng
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Department of Dermatology, National Cheng Kung University Medical College, Tainan, Taiwan.
authors.forename: Hamm-Ming
authors.initials: HM
authors.lastname: Sheu
authors.affiliation: Institute of Clinical Pharmacy, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Jui-Chen
authors.initials: JC
authors.lastname: Tsai
authors.affiliation: Division of Urology, Department of Surgery, Chi Mei Medical Center, Liouying, Taiwan; Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan.
authors.forename: Chia-Ho
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Department of Environmental and Occupational Health, National Cheng Kung University Medical College, Tainan, Taiwan; Department of Biomedical Informatics, Asia University, Taichung, Taiwan.
authors.forename: Ying-Jan
authors.initials: YJ
authors.lastname: Wang
authors.affiliation: Department of Environmental and Occupational Health, National Cheng Kung University Medical College, Tainan, Taiwan; Department of Cosmetic Science and Institute of Cosmetic Science, Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
authors.forename: Bour-Jr
authors.initials: BJ
authors.lastname: Wang
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D002478:Cells, Cultured; D002857:Chromium / Q000633:toxicity*; D017449:Dermatitis, Allergic Contact / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D004353:Drug Evaluation, Preclinical; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006168:Guinea Pigs; D053582:Interleukin-1alpha / Q000096:biosynthesis* / Q000235:genetics; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D016328:NF-kappa B / Q000502:physiology; D051058:Oncogene Protein v-akt / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000975:Antioxidants; D053582:Interleukin-1alpha; D016328:NF-kappa B; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D002857:Chromium; C074702:chromium hexavalent ion; D051058:Oncogene Protein v-akt; D000111:Acetylcysteine