{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T23:43:02Z","timestamp":1790379782040,"version":"4.1.0"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2019,2,8]],"date-time":"2019-02-08T00:00:00Z","timestamp":1549584000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81560015"],"award-info":[{"award-number":["81560015"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Inflammation"],"published-print":{"date-parts":[[2019,4]]},"DOI":"10.1007\/s10753-018-00956-1","type":"journal-article","created":{"date-parts":[[2019,2,7]],"date-time":"2019-02-07T22:39:48Z","timestamp":1549579188000},"page":"471-484","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["High-Dose Paraquat Induces Human Bronchial 16HBE Cell Death and Aggravates Acute Lung Intoxication in Mice by Regulating Keap1\/p65\/Nrf2 Signal Pathway"],"prefix":"10.1007","volume":"42","author":[{"given":"Jiexiong","family":"Yao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihua","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenlin","family":"Tai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhao","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjuan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Pu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Du","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1810-1822","authenticated-orcid":false,"given":"Zhaoxing","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,2,8]]},"reference":[{"issue":"15","key":"956_CR1","doi-asserted-by":"publisher","first-page":"e9621","DOI":"10.1097\/MD.0000000000009621","volume":"97","author":"N Elenga","year":"2018","unstructured":"Elenga, N., C. Merlin, R. le Guern, R. Kom-Tchameni, Y.M. Ducrot, M. Pradier, B. Ntab, K.A. Dinh-van, M. Sobesky, D. Mathieu, J.M. Dueymes, G. Egmann, H. Kallel, and M. Mathieu-Nolf. 2018. Clinical features and prognosis of paraquat poisoning in French Guiana: a review of 62 cases. Medicine (Baltimore) 97 (15): e9621.","journal-title":"Medicine (Baltimore)"},{"issue":"6","key":"956_CR2","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1002\/ajim.22835","volume":"61","author":"SH Zyoud","year":"2018","unstructured":"Zyoud, S.H. 2018. Investigating global trends in paraquat intoxication research from 1962 to 2015 using bibliometric analysis. American Journal of Industrial Medicine 61 (6): 462\u2013470.","journal-title":"American Journal of Industrial Medicine"},{"issue":"5","key":"956_CR3","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1093\/carcin\/19.5.809","volume":"19","author":"M Dusinska","year":"1998","unstructured":"Dusinska, M., et al. 1998. Responses of alveolar macrophages and epithelial type II cells to oxidative DNA damage caused by paraquat. Carcinogenesis 19 (5): 809\u2013812.","journal-title":"Carcinogenesis"},{"key":"956_CR4","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1016\/j.neuro.2018.04.006","volume":"66","author":"N S","year":"2018","unstructured":"S, N., and T. Shivanandappa. 2018. Neuroprotective action of 4-hydroxyisophthalic acid against paraquat-induced motor impairment involves amelioration of mitochondrial damage and neurodegeneration in Drosophila. Neurotoxicology 66: 160\u2013169.","journal-title":"Neurotoxicology"},{"issue":"6","key":"956_CR5","doi-asserted-by":"publisher","first-page":"503","DOI":"10.4062\/biomolther.2014.115","volume":"22","author":"HJ Seo","year":"2014","unstructured":"Seo, H.J., S.J. Choi, and J.H. Lee. 2014. Paraquat induces apoptosis through cytochrome C release and ERK activation. Biomolecules & Therapeutics (Seoul) 22 (6): 503\u2013509.","journal-title":"Biomolecules & Therapeutics (Seoul)"},{"issue":"1","key":"956_CR6","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1093\/toxsci\/kfu158","volume":"142","author":"Q Wang","year":"2014","unstructured":"Wang, Q., L. Yang, Y. Hua, S. Nair, X. Xu, and J. Ren. 2014. AMP-activated protein kinase deficiency rescues paraquat-induced cardiac contractile dysfunction through an autophagy-dependent mechanism. Toxicological Sciences 142 (1): 6\u201320.","journal-title":"Toxicological Sciences"},{"key":"956_CR7","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1007\/s12640-018-9916-0","volume":"34","author":"D Colle","year":"2018","unstructured":"Colle, D., M. Farina, S. Ceccatelli, and M. Raciti. 2018. Paraquat and maneb exposure alters rat neural stem cell proliferation by inducing ROS generation: new insights on pesticide-induced neurodevelopmental toxicity. Neurotoxicity Research 34: 820\u2013833.","journal-title":"Neurotoxicity Research"},{"key":"956_CR8","volume":"99","author":"E Possik","year":"2015","unstructured":"Possik, E., and A. Pause. 2015. Measuring ROS generation resistance of Caenorhabditis elegans in 96-well microtiter plates. Journal of Visualized Experiments 99: e52746.","journal-title":"Journal of Visualized Experiments"},{"issue":"2","key":"956_CR9","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.cbi.2013.09.010","volume":"206","author":"X Chang","year":"2013","unstructured":"Chang, X., W. Lu, T. Dou, X. Wang, D. Lou, X. Sun, and Z. Zhou. 2013. Paraquat inhibits cell viability via enhanced ROS generation and apoptosis in human neural progenitor cells. Chemico-Biological Interactions 206 (2): 248\u2013255.","journal-title":"Chemico-Biological Interactions"},{"key":"956_CR10","first-page":"9396425","volume":"2017","author":"NA El-Boghdady","year":"2017","unstructured":"El-Boghdady, N.A., and N.F. Abdeltawab. 2017. Resveratrol and Montelukast alleviate paraquat-induced hepatic injury in mice: modulation of ROS generation, inflammation. Apoptosis 2017: 9396425.","journal-title":"Apoptosis"},{"key":"956_CR11","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.neulet.2016.10.050","volume":"636","author":"T Jaroonwitchawan","year":"2017","unstructured":"Jaroonwitchawan, T., N. Chaicharoenaudomrung, J. Namkaew, and P. Noisa. 2017. Curcumin attenuates paraquat-induced cell death in human neuroblastoma cells through modulating ROS generation and autophagy. Neuroscience Letters 636: 40\u201347.","journal-title":"Neuroscience Letters"},{"issue":"3","key":"956_CR12","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1038\/cdd.2014.150","volume":"22","author":"G Filomeni","year":"2015","unstructured":"Filomeni, G., D. De Zio, and F. Cecconi. 2015. ROS generation and autophagy: the clash between damage and metabolic needs. Cell Death and Differentiation 22 (3): 377\u2013388.","journal-title":"Cell Death and Differentiation"},{"issue":"1","key":"956_CR13","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1124\/jpet.112.194142","volume":"342","author":"X He","year":"2012","unstructured":"He, X., L. Wang, G. Szklarz, Y. Bi, and Q. Ma. 2012. Resveratrol inhibits paraquat-induced ROS generation and fibrogenic response by activating the nuclear factor erythroid 2-related factor 2 pathway. The Journal of Pharmacology and Experimental Therapeutics 342 (1): 81\u201390.","journal-title":"The Journal of Pharmacology and Experimental Therapeutics"},{"issue":"2","key":"956_CR14","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.intimp.2013.06.005","volume":"17","author":"K Amirshahrokhi","year":"2013","unstructured":"Amirshahrokhi, K. 2013. Anti-inflammatory effect of thalidomide in paraquat-induced pulmonary injury in mice. International Immunopharmacology 17 (2): 210\u2013215.","journal-title":"International Immunopharmacology"},{"key":"956_CR15","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.fsi.2018.06.030","volume":"80","author":"H Wang","year":"2018","unstructured":"Wang, H., L. Pan, L. Si, and J. Miao. 2018. The role of Nrf2-Keap1 signaling pathway in the antioxidant defense response induced by PAHs in the calm Ruditapes philippinarum. Fish & Shellfish Immunology 80: 325\u2013334.","journal-title":"Fish & Shellfish Immunology"},{"issue":"3","key":"956_CR16","doi-asserted-by":"publisher","first-page":"R83","DOI":"10.1530\/JOE-14-0662","volume":"225","author":"B Chen","year":"2015","unstructured":"Chen, B., Y. Lu, Y. Chen, and J. Cheng. 2015. The role of Nrf2 in ROS generation-induced endothelial injuries. The Journal of Endocrinology 225 (3): R83\u2013R99.","journal-title":"The Journal of Endocrinology"},{"issue":"5","key":"956_CR17","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1016\/j.cellsig.2011.01.014","volume":"23","author":"M Yu","year":"2011","unstructured":"Yu, M., H. Li, Q. Liu, F. Liu, L. Tang, C. Li, Y. Yuan, Y. Zhan, W. Xu, W. Li, H. Chen, C. Ge, J. Wang, and X. Yang. 2011. Nuclear factor p65 interacts with Keap1 to repress the Nrf2-ARE pathway. Cellular Signalling 23 (5): 883\u2013892.","journal-title":"Cellular Signalling"},{"key":"956_CR18","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.redox.2015.06.020","volume":"6","author":"AK Verma","year":"2015","unstructured":"Verma, A.K., A. Yadav, J. Dewangan, S.V. Singh, M. Mishra, P.K. Singh, and S.K. Rath. 2015. Isoniazid prevents Nrf2 translocation by inhibiting ERK1 phosphorylation and induces ROS generation and apoptosis. Redox Biology 6: 80\u201392.","journal-title":"Redox Biology"},{"issue":"7","key":"956_CR19","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1007\/s00011-015-0834-9","volume":"64","author":"S Qin","year":"2015","unstructured":"Qin, S., R.H. du, S.S. Yin, X.F. Liu, G.L. Xu, and W. Cao. 2015. Nrf2 is essential for the anti-inflammatory effect of carbon monoxide in LPS-induced inflammation. Inflammation Research 64 (7): 537\u2013548.","journal-title":"Inflammation Research"},{"key":"956_CR20","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.toxlet.2018.04.030","volume":"292","author":"H Fan","year":"2018","unstructured":"Fan, H., H. Huang, L. Hu, W. Zhu, Y. Yu, J. Lou, L. Hu, and F. Chen. 2018. The activation of STIM1 mediates S-phase arrest and cell death in paraquat induced acute lung intoxication. Toxicology Letters 292: 123\u2013135.","journal-title":"Toxicology Letters"},{"key":"956_CR21","doi-asserted-by":"crossref","unstructured":"Martinez-Perez, D.A., M. Jimenez-Del-Rio, and C. Velez-Pardo. 2018. Correction to: Epigallocatechin-3-gallate protects and prevents paraquat-induced oxidative stress and neurodegeneration in knockdown dj-1-beta Drosophila melanogaster. Neurotoxicity Research 34 (3): 417.","DOI":"10.1007\/s12640-018-9919-x"},{"key":"956_CR22","doi-asserted-by":"publisher","first-page":"e965","DOI":"10.1038\/cddis.2013.478","volume":"4","author":"J Hanus","year":"2013","unstructured":"Hanus, J., H. Zhang, Z. Wang, Q. Liu, Q. Zhou, and S. Wang. 2013. Induction of necrotic cell death by ROS generation in retinal pigment epithelial cells. Cell Death & Disease 4: e965.","journal-title":"Cell Death & Disease"},{"issue":"6","key":"956_CR23","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1080\/15548627.2015.1042195","volume":"11","author":"VP Tan","year":"2015","unstructured":"Tan, V.P., and S. Miyamoto. 2015. HK2\/hexokinase-II integrates glycolysis and autophagy to confer cellular protection. Autophagy 11 (6): 963\u2013964.","journal-title":"Autophagy"},{"issue":"40","key":"956_CR24","doi-asserted-by":"publisher","first-page":"5105","DOI":"10.1038\/onc.2014.458","volume":"34","author":"S Fulda","year":"2015","unstructured":"Fulda, S., and D. Kogel. 2015. Cell death by autophagy: emerging molecular mechanisms and implications for cancer therapy. Oncogene 34 (40): 5105\u20135113.","journal-title":"Oncogene"},{"key":"956_CR25","doi-asserted-by":"publisher","first-page":"e1195","DOI":"10.1038\/cddis.2014.157","volume":"5","author":"M Hussong","year":"2014","unstructured":"Hussong, M., S.T. B\u00f6rno, M. Kerick, A. Wunderlich, A. Franz, H. S\u00fcltmann, B. Timmermann, H. Lehrach, M. Hirsch-Kauffmann, and M.R. Schweiger. 2014. The bromodomain protein BRD4 regulates the KEAP1\/NRF2-dependent ROS generation response. Cell Death & Disease 5: e1195.","journal-title":"Cell Death & Disease"},{"issue":"7","key":"956_CR26","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1007\/s12098-013-1155-z","volume":"81","author":"W Ge","year":"2014","unstructured":"Ge, W., H.L. Wang, and R.P. Sun. 2014. Clinical characteristics of paraquat poisoning in 22 Chinese children. Indian Journal of Pediatrics 81 (7): 670\u2013674.","journal-title":"Indian Journal of Pediatrics"},{"key":"956_CR27","doi-asserted-by":"crossref","unstructured":"Yang, W., W. Liu, W. Yu, D. Fei, X. Meng, S. Yang, S. Meng, and M. Zhao. 2018. Angptl2 deficiency attenuates paraquat (PQ)-induced lung injury in mice by altering inflammation, oxidative stress and fibrosis through NF-kappaB pathway. Biochemical and Biophysical Research Communications 503 (1): 94\u2013101.","DOI":"10.1016\/j.bbrc.2018.05.186"},{"issue":"3","key":"956_CR28","doi-asserted-by":"publisher","first-page":"193","DOI":"10.2131\/jts.43.193","volume":"43","author":"N Hirayama","year":"2018","unstructured":"Hirayama, N., T. Aki, T. Funakoshi, K. Noritake, K. Unuma, and K. Uemura. 2018. Necrosis in human neuronal cells exposed to paraquat. The Journal of Toxicological Sciences 43 (3): 193\u2013202.","journal-title":"The Journal of Toxicological Sciences"},{"issue":"9","key":"956_CR29","first-page":"671","volume":"26","author":"H Li","year":"2014","unstructured":"Li, H., et al. 2014. The effect of selective phosphatase inhibitors Salubrinal on autophagy and apoptosis in the lung tissue of rats with acute paraquat poisoning. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 26 (9): 671\u2013675.","journal-title":"Zhonghua Wei Zhong Bing Ji Jiu Yi Xue"},{"key":"956_CR30","doi-asserted-by":"publisher","first-page":"1493","DOI":"10.1007\/s11011-018-0256-9","volume":"33","author":"IO Ishola","year":"2018","unstructured":"Ishola, I.O., A.A. Akinyede, T.P. Adeluwa, and C. Micah. 2018. Novel action of vinpocetine in the prevention of paraquat-induced parkinsonism in mice: involvement of ROS generation and neuroinflammation. Metabolic Brain Disease 33: 1493\u20131500.","journal-title":"Metabolic Brain Disease"},{"issue":"4","key":"956_CR31","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1159\/000366330","volume":"34","author":"JW Chen","year":"2014","unstructured":"Chen, J.W., B.B. Ni, B. Li, Y.H. Yang, S.D. Jiang, and L.S. Jiang. 2014. The responses of autophagy and apoptosis to ROS generation in nucleus pulposus cells: implications for disc degeneration. Cellular Physiology and Biochemistry 34 (4): 1175\u20131189.","journal-title":"Cellular Physiology and Biochemistry"},{"issue":"2","key":"956_CR32","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1007\/s00394-013-0562-2","volume":"53","author":"HC Hsu","year":"2014","unstructured":"Hsu, H.C., C.Y. Chen, C.H. Chiang, and M.F. Chen. 2014. Eicosapentaenoic acid attenuated ROS generation-induced cardiomyoblast apoptosis by activating adaptive autophagy. European Journal of Nutrition 53 (2): 541\u2013547.","journal-title":"European Journal of Nutrition"},{"issue":"9","key":"956_CR33","doi-asserted-by":"publisher","first-page":"1499","DOI":"10.1007\/s00299-015-1802-0","volume":"34","author":"D Zhang","year":"2015","unstructured":"Zhang, D., L. Ren, G.Q. Chen, J. Zhang, B.M. Reed, and X.H. Shen. 2015. ROS-induced ROS generation and apoptosis-like event directly affect the cell viability of cryopreserved embryogenic callus in Agapanthus praecox. Plant Cell Reports 34 (9): 1499\u20131513.","journal-title":"Plant Cell Reports"}],"container-title":["Inflammation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s10753-018-00956-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10753-018-00956-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10753-018-00956-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,2,7]],"date-time":"2020-02-07T19:10:27Z","timestamp":1581102627000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s10753-018-00956-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,8]]},"references-count":33,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,4]]}},"alternative-id":["956"],"URL":"https:\/\/doi.org\/10.1007\/s10753-018-00956-1","relation":{},"ISSN":["0360-3997","1573-2576"],"issn-type":[{"value":"0360-3997","type":"print"},{"value":"1573-2576","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,8]]},"assertion":[{"value":"8 February 2019","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with Ethical Standards"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}}]}}