title: Cepharanthine mitigates pro-inflammatory cytokine response in lung injury induced by hemorrhagic shock/resuscitation in rats.
abstract: BACKGROUND
  Cepharanthine possesses strong anti-inflammation capacity. We sought to clarify whether cepharanthine could mitigate pro-inflammatory cytokine production in acute lung injury induced by hemorrhagic shock/resuscitation (HS/RES). The involvement of heme oxygenase-1 (HO-1) was also investigated.
  
  
  METHODS
  Male Sprague Dawley rats were allocated to receive HS/RES, HS/RES plus iv cepharanthine or HS/RES plus cepharanthine plus the HO-1 activity inhibitor tin protoporphyrin (SnPP) and denoted as the HS/RES, HS/RES+CEP, and HS/RES+CEP+SnPP group, respectively. HS/RES was achieved by blood drawing to lower mean arterial pressure (40-45 mmHg for 60 min) followed by shed blood/saline mixtures re-infusion. The rats were monitored for another 5h before sacrifice.
  
  
  RESULTS
  Arterial blood gas, lung permeability and histologic assays (including histopathology, neutrophil infiltration, and lung water content) confirmed that HS/RES induced significant lung injury. Significant increases in pulmonary levels of tumor necrosis factor-α, interleukin-1β, interleukin-6, prostaglandin E2 and cyclooxygenase-2 confirmed that HS/RES induced a significant inflammatory response in the lungs. Cepharanthine significantly attenuated the pulmonary pro-inflammatory cytokine production and lung injury induced by HS/RES. However, the protective effects of cepharanthine were blocked by SnPP, the potent HO-1 activity inhibitor.
  
  
  CONCLUSIONS
  Cepharanthine significantly mitigates pro-inflammatory cytokine response in acute lung injury induced by HS/RES in rats. The mechanism may involve the HO-1 pathway.
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Anesthesiology, Taipei Tzu Chi Hospital, Taipei, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan. Electronic address: dr_mck@yahoo.com.tw.
authors.forename: Ming-Chang
authors.initials: MC
authors.lastname: Kao
authors.affiliation: Department of Anesthesiology, Taipei Tzu Chi Hospital, Taipei, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan. Electronic address: doctor@pain.tw.
authors.forename: Chen-Hsien
authors.initials: CH
authors.lastname: Yang
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: sheujr@tmu.edu.tw.
authors.forename: Joen-Rong
authors.initials: JR
authors.lastname: Sheu
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Anesthesiology, Taipei Tzu Chi Hospital, Taipei, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan. Electronic address: huangcj1112@gmail.com.
authors.forename: Chun-Jen
authors.initials: CJ
authors.lastname: Huang
mesh_terms: D000818:Animals; D044182:Benzylisoquinolines / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D008168:Lung / Q000473:pathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000378:metabolism*; D052117:Benzodioxoles
chemical_list: D044182:Benzylisoquinolines; D016207:Cytokines; D006419:Heme Oxygenase (Decyclizing); D018836:Inflammation Mediators; C006947:cepharanthine; D052117:Benzodioxoles; C491523:Hmox1 protein, rat
keywords: Anti-inflammatory; Heme oxygenase-1; Interleukin; Tin protoporphyrin; Tumor necrosis factor-α