title: Effects of repeated Cr(VI) intratracheal instillation on club (Clara) cells and activation of nuclear factor-kappa B pathway via oxidative stress.
abstract: Hexavalent chromium [Cr(VI)] exposure is known to induce respiratory inflammation and contribute to lung cancer development, but little is known about its target cell type in lung. In the current study, we investigated the effects of repeated Cr(VI) intratracheal instillation on club (Clara) cells and club (Clara) cell secretory protein (CC16) in rats and explored whether the nuclear factor-kappa B (NF-κB) related pathway was involved. We also studied the role of orally delivered Zn against Cr-induced adverse health effects. For four weeks, sixty Sprague-Dawley male rats received weekly intratracheal instillation of potassium dichromate (K2Cr2O7) at 0, 0.063 and 0.630mgCr/kg with or without daily intragastric administration of zinc sulfate (ZnSO4) at 10mg Zn/kg. Results showed that exposure to Cr(VI) significantly increased the organ coefficient of lung (organ weight as a percentage of body weight), albumin and total protein level in bronchoalveolar lavage fluid (BALF), indicating lung injury and compromised bronchoalveolar/blood barrier (BA/BB) integrity. With increasing Cr(VI) dose, the secretion of CC16 decreased in a dose-dependent manner, suggesting that CC16 can serve as a peripheral biomarker for club cell damage during early lung injury induced by Cr(VI). Increased expression of NF-κB were observed in club cells in both Cr-exposed groups, indicating upregulation of NF-κB, which can be induced by reactive oxygen species (ROS) generated by club cells during Cr reduction with repetitive Cr(VI) exposure. Cr-induced DNA damage was also observed, as significant increase of 8-OHdG was found with Cr exposure at 0.630mg/kg week. Oral Zn supplementation did not alleviate changes in serum CC16 level under Cr(VI) exposure, indicating its failure in protecting against Cr(VI)-induced club cell damage.
authors.affiliation: Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, #38 Xueyuan Road, Beijing 100191, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, #38 Xueyuan Road, Beijing 100191, PR China.
authors.forename: Yanshuang
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, #38 Xueyuan Road, Beijing 100191, PR China.
authors.forename: Ji
authors.initials: J
authors.lastname: Pu
authors.affiliation: Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, #38 Xueyuan Road, Beijing 100191, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, #38 Xueyuan Road, Beijing 100191, PR China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, #38 Xueyuan Road, Beijing 100191, PR China.
authors.forename: Zhangjian
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, #38 Xueyuan Road, Beijing 100191, PR China.
authors.forename: Tian
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, #38 Xueyuan Road, Beijing 100191, PR China.
authors.forename: Yongen
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, #38 Xueyuan Road, Beijing 100191, PR China. Electronic address: jiaguangjia@bjmu.edu.cn.
authors.forename: Guang
authors.initials: G
authors.lastname: Jia
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000284:Administration, Oral; D056809:Alveolar Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D018916:Blood-Aqueous Barrier / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002199:Capillary Permeability / Q000187:drug effects; D002857:Chromium / Q000633:toxicity*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D004305:Dose-Response Relationship, Drug; D005919:Glomerular Filtration Rate / Q000187:drug effects; D055370:Lung Injury / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D011192:Potassium Dichromate / Q000633:toxicity*; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D015854:Up-Regulation; D014598:Uteroglobin / Q000097:blood; D019287:Zinc Sulfate / Q000008:administration & dosage
chemical_list: D015415:Biomarkers; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C556391:Scgb1a1 protein, rat; D012709:Serum Albumin; D002857:Chromium; C074702:chromium hexavalent ion; D019287:Zinc Sulfate; D000080242:8-Hydroxy-2'-Deoxyguanosine; D014598:Uteroglobin; D003849:Deoxyguanosine; D011192:Potassium Dichromate
keywords: Animal; Biomarker; Club (Clara) cell; Hexavalent chromium; NF-κB; Oxidative stress; experiment