title: The role of p38 MAPK in acute paraquat-induced lung injury in rats.
abstract: BACKGROUND
  Paraquat (PQ; 1,1'-dimethyl-4,4'-bipyridinium dichloride) is highly toxic and accounts for a large proportion of the herbicide poisonings seen in clinic. The major cause of mortality is respiratory failure. The p38 mitogen-activated protein kinase (MAPK) signal transduction pathway coordinates various cellular stress responses that have been shown to participate in the pathogenesis of PQ-induced lung injury.
  
  
  OBJECTIVE
  To evaluate the effect of the specific p38 MAPK inhibitor SB203580 on PQ-induced lung injury and cytokine secretion.
  
  
  METHODS
  In groups of 24, rats were treated with PQ, PQ and SB203580 (SB + PQ), SB203580 alone (SB) or normal saline (control group). Six rats from each group were euthanized at 1, 3, 5 or 7 d. Pathology of lung specimens was scored through hematoxylin and eosin staining. Edema in the lung was quantified from wet-to-dry weight ratios. p38 and p-p38MAPK proteins were measured via electrochemiluminescent Western blots. tumor necrosis factor (TNF)-alpha and interleukin-1 beta (IL-1β) concentrations in lung specimens and bronchoalveolar lavage fluid (BALF) were quantified via enzyme-linked immunosorbent assay.
  
  
  RESULTS
  The mortality rate of the SB + PQ group (16.7%) was significantly lower than that of the PQ group (33.3%; p < 0.05). The PQ group had significantly higher pulmonary histology scores, wet-to-dry weight ratios and phosphorylated p-p38 MAPK levels, as well as higher IL-1β and TNF-alpha levels in BALF and lung tissues, that did the SB + PQ and control groups (p < 0.05, all).
  
  
  CONCLUSIONS
  The data suggest that the p38 MAPK signaling pathway has an important role in regulating the production of IL-1β and TNF-alpha in PQ-induced lung injury in rats.
authors.affiliation: Department of Intensive Care Unit, Jiangsu Provincial Hospital of Traditional Chinese Medicine , Nanjing , China .
authors.forename: Ying-hao
authors.initials: YH
authors.lastname: Pei
authors.forename: Xiao-min
authors.initials: XM
authors.lastname: Cai
authors.forename: Jiao
authors.initials: J
authors.lastname: Chen
authors.forename: Bao-di
authors.initials: BD
authors.lastname: Sun
authors.forename: Zhao-rui
authors.initials: ZR
authors.lastname: Sun
authors.forename: Xing
authors.initials: X
authors.lastname: Wang
authors.forename: Xiao-min
authors.initials: XM
authors.lastname: Qian
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000473:pathology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D004797:Enzyme-Linked Immunosorbent Assay; D007093:Imidazoles / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D010269:Paraquat / Q000633:toxicity*; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D007093:Imidazoles; D053583:Interleukin-1beta; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; D010269:Paraquat
keywords: Interleukin 1 beta; lung injury; mitogen-activated protein kinase; paraquat; tumor necrosis factor-alpha