title: Sulforaphane pretreatment prevents systemic inflammation and renal injury in response to cardiopulmonary bypass.
abstract: OBJECTIVE
  Systemic inflammatory responses are a major cause of morbidity and mortality in patients undergoing cardiac surgery with cardiopulmonary bypass. However, the underlying molecular mechanisms for systemic inflammation in response to cardiopulmonary bypass are poorly understood.
  
  
  METHODS
  A porcine model was established to study the signaling pathways that promote systemic inflammation in response to cardiac surgery with cardiopulmonary bypass under well-controlled experimental conditions. The influence of sulforaphane, an anti-inflammatory compound derived from green vegetables, on inflammation and injury in response to cardiopulmonary bypass was also studied. Intracellular staining and flow cytometry were performed to measure phosphorylation of p38 mitogen-activated protein kinase and the transcription factor nuclear factor-κB in granulocytes and mononuclear cells.
  
  
  RESULTS
  Surgery with cardiopulmonary bypass for 1 to 2 hours enhanced phosphorylation of p38 (2.5-fold) and nuclear factor-κB (1.6-fold) in circulating mononuclear cells. Cardiopulmonary bypass also modified granulocytes by activating nuclear factor-κB (1.6-fold), whereas p38 was not altered. Histologic analyses revealed that cardiopulmonary bypass promoted acute tubular necrosis. Pretreatment of animals with sulforaphane reduced p38 (90% reduction) and nuclear factor-κB (50% reduction) phosphorylation in leukocytes and protected kidneys from injury.
  
  
  CONCLUSIONS
  Systemic inflammatory responses after cardiopulmonary bypass were associated with activation of p38 and nuclear factor-κB pathways in circulating leukocytes. Inflammatory responses to cardiopulmonary bypass can be reduced by sulforaphane, which reduced leukocyte activation and protected against renal injury.
authors: BHF Cardiovascular Sciences Unit, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors: Bao
authors: B
authors: Nguyen
authors: Department of Cardiovascular Science, University of Sheffield, Sheffield, United Kingdom.
authors: Le
authors: L
authors: Luong
authors: BHF Cardiovascular Sciences Unit, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors: Hatam
authors: H
authors: Naase
authors: Department of Anaesthesia, Toronto General Hospital, Toronto, Ontario, Canada.
authors: Marc
authors: M
authors: Vives
authors: BHF Cardiovascular Sciences Unit, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors: Gentjan
authors: G
authors: Jakaj
authors: BHF Cardiovascular Sciences Unit, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors: Jonathan
authors: J
authors: Finch
authors: BHF Cardiovascular Sciences Unit, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors: Joseph
authors: J
authors: Boyle
authors: Department of Clinical Perfusion Science, Hammersmith Hospital, London, United Kingdom.
authors: John W
authors: JW
authors: Mulholland
authors: School of Pharmacy, Sungkyunkwan University, Seoul, Republic of Korea.
authors: Jong-hwan
authors: JH
authors: Kwak
authors: School of Pharmacy, Sungkyunkwan University, Seoul, Republic of Korea.
authors: Suhkneung
authors: S
authors: Pyo
authors: BHF Cardiovascular Sciences Unit, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors: Amalia
authors: A
authors: de Luca
authors: Department of Cardiothoracic Surgery, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors: Thanos
authors: T
authors: Athanasiou
authors: Department of Cardiothoracic Surgery, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors: Gianni
authors: G
authors: Angelini
authors: Department of Cardiothoracic Surgery, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors: Jon
authors: J
authors: Anderson
authors: BHF Cardiovascular Sciences Unit, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors: Dorian O
authors: DO
authors: Haskard
authors: Department of Cardiovascular Science, University of Sheffield, Sheffield, United Kingdom. Electronic address: paul.evans@sheffield.ac.uk.
authors: Paul C
authors: PC
authors: Evans
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D017879:Isothiocyanates / Q000494:pharmacology*; D007683:Kidney Tubular Necrosis, Acute / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects; D013454:Sulfoxides; D013552:Swine; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D017879:Isothiocyanates; D016328:NF-kappa B; D013454:Sulfoxides; D048051:p38 Mitogen-Activated Protein Kinases; C016766:sulforaphane