title: Chloroquine attenuates paraquat-induced lung injury in mice by altering inflammation, oxidative stress and fibrosis.
abstract: Paraquat is one of the most extensively used herbicides and has high toxicity for humans and animals. However, there is no effective treatment for paraquat poisoning. The aim of the present study was to evaluate the effects of chloroquine on paraquat-induced lung injury in mice. Mice received a single intraperitoneal injection of paraquat and a daily intraperitoneal injection of the indicated dosages of chloroquine or dexamethasone. The histological changes, inflammation and oxidative stress in the lungs were examined at day 3, and the degree of pulmonary fibrosis was examined at day 28. H&E staining showed that chloroquine markedly attenuated lung injury induced by paraquat. In addition, the inflammatory responses induced by paraquat were inhibited after treatment with chloroquine, as indicated by the decreased number of leukocytes, the reduced levels of TNF-α, IL-1β and IL-6 in the bronchoalveolar lavage fluid, the reduced NO content, and downregulation of iNOS expression in lung tissues. No different effect was found between high-dose chloroquine and dexamethasone. Additionally, the treatment with chloroquine increased the activity of SOD and decreased the level of MDA in the lung tissues. The expressions of the anti-oxidative proteins, Nrf2, HO-1 and NQO1, were also upregulated by chloroquine treatment. The high-dose chloroquine was more effective than dexamethasone in its anti-oxidation ability. Finally, the results of Masson's staining illustrated that chloroquine markedly attenuated fibrosis in the paraquat-exposed lungs. Immunohistochemistry staining showed that the expressions of the pro-fibrotic proteins TGF-β and α-SMA were downregulated after treatment with chloroquine. In conclusion, chloroquine effectively attenuated paraquat-induced lung injury in mice.
authors.affiliation: Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Wu
authors.affiliation: Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Lichun
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Tiegang
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China. Electronic address: zhaom@sj-hospital.org.
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
mesh_terms: D000199:Actins / Q000378:metabolism; D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002738:Chloroquine / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010269:Paraquat; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy*; D000072105:Superoxide Dismutase-1 / Q000378:metabolism
chemical_list: D000199:Actins; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; C544013:alpha-smooth muscle actin, mouse; D002738:Chloroquine; C000606291:Sod1 protein, mouse; D000072105:Superoxide Dismutase-1; D010269:Paraquat
keywords: Chloroquine; Fibrosis; Inflammation; Oxidative stress; Paraquat