Ebselen improves ischemia-reperfusion injury after rat lung transplantation.
The heterocyclic organic compound ebselen (2-phenyl-1,2-benizsoselenazol-3(2H)-one) is a glutathione peroxidase mimick with protective properties against oxidative injury. Ebselen also has anti-inflammatory activity, including attenuation of tumor necrosis factor release and increase of interleukin-10, as shown in vivo, in inflammatory and ischemia-reperfusion injuries, including those of the lung. This study was designed to assess its effect on severe ischemia-reperfusion injury in a model of left-sided rat lung isotransplantation. Orthotopic single left-sided lung allotransplantation (Wistar to Wistar) was performed in female rats after a total ischemic time of 18 h. In nine recipients given 500 mg/kg oral ebselen 1 h before transplantation, graft PaO(2)/FiO(2) was improved 24 h after transplantation, as evidenced with a mean (standard deviation) PaO(2) of 139 (61) mmHg vs. eight controls with 65 (33) mmHg (p = 0.009). Bronchoalveolar PMN count was reduced to approximately 50% in the ebselen group compared with controls, whereas no difference in the tumor necrosis factor content was found. We conclude that the improvement of lung function in ebselen-treated transplanted rats is mainly the result of the anti-inflammatory activity of the drug during reperfusion.
Hamacher
Jürg
J
Biochemical Pharmacology, University of Konstanz, Konstanz, Germany. hamacher@greenmail.ch
Stammberger
Uz
U
Weber
Elvira
E
Lucas
Rudolf
R
Wendel
Albrecht
A
D055371:Acute Lung Injury / Q000209:etiology / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D001393:Azoles / Q000008:administration & dosage / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D016753:Interleukin-10 / Q000378:metabolism; D054833:Isoindoles; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D016040:Lung Transplantation / Q000009:adverse effects*; D020556:Neutrophil Infiltration / Q000187:drug effects; D016566:Organoselenium Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000209:etiology / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D012720:Severity of Illness Index; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C042986:ebselen