title: Cepharanthine mitigates lung injury in lower limb ischemia-reperfusion.
abstract: BACKGROUND
  Oxidation and inflammation caused by lower limb ischemia-reperfusion (I/R) readily induce lung injury. We elucidated whether cepharanthine, a potent antioxidative and anti-inflammatory drug, can mitigate lung injury induced by lower limb I/R. Role of heme oxygenase 1 (HO-1) was also investigated.
  
  
  METHODS
  Adult male Sprague-Dawley rats were randomized to receive I/R, I/R plus cepharanthine, or I/R plus cepharanthine plus the HO-1 activity inhibitor tin protoporphyrin (SnPP; n = 12 in each group). Sham control groups were run simultaneously. I/R was induced by applying rubber band tourniquets high around each thigh for 3 h followed by reperfusion for 24 h.
  
  
  RESULTS
  Rats receiving I/R had significant increases in concentrations of nitric oxide, malondialdehyde (lipid peroxidation marker), and inflammatory molecules (including interleukin 6, macrophage inflammatory protein 2, and prostaglandin E2) in plasma, and the lungs, indicating that I/R caused significant oxidation and inflammation in rats. Rats receiving I/R also had significant increases in concentration of phosphorylated inhibitor-κB, indicating that I/R caused significant nuclear factor κB activation. Assays of arterial blood gas, biochemistry, and histopathology confirmed that I/R-induced significant lung injury in rats. Cepharanthine significantly reduced the oxidation, inflammation, nuclear factor κB activation, and lung injury induced by I/R. Of note, cepharanthine significantly enhanced pulmonary HO-1 expression after I/R. Moreover, these previously mentioned effects of cepharanthine were partially reversed by inhibiting the activity of HO-1.
  
  
  CONCLUSIONS
  Cepharanthine mitigates lung injury induced by bilateral lower limb I/R in rats. The mechanisms may involve its effects on reducing oxidation and inflammation. The mechanisms may also involve enhancing HO-1 expression.
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Anesthesiology, Taipei Tzu Chi Hospital, New Taipei City, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan.
authors.forename: Ming-Chang
authors.initials: MC
authors.lastname: Kao
authors.affiliation: Department of Anesthesiology, Taipei Tzu Chi Hospital, New Taipei City, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan.
authors.forename: Chen-Hsien
authors.initials: CH
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Taipei Tzu Chi Hospital, New Taipei City, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan.
authors.forename: Wei-Chih
authors.initials: WC
authors.lastname: Chou
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, New Taipei City, 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: D055371:Acute Lung Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D044182:Benzylisoquinolines / Q000627:therapeutic use*; D001784:Blood Gas Analysis; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D020672:I-kappa B Proteins / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D009569:Nitric Oxide / Q000097:blood; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D031607:Stephania / Q000737:chemistry; D052117:Benzodioxoles
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D044182:Benzylisoquinolines; D051546:Cyclooxygenase 2; D051547:Heme Oxygenase-1; D020672:I-kappa B Proteins; D008315:Malondialdehyde; D009569:Nitric Oxide; D010936:Plant Extracts; C006947:cepharanthine; D052117:Benzodioxoles; C489691:Ptgs2 protein, rat
keywords: Chemokine; Cytokine; Inflammation; Oxidative stress