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Salvage of nonischemic control lung from injury by unilateral ischemic lung with apocynin, a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, in isolated perfused rat lung.

Abstract
Ischemia reperfusion (I/R) injury of the lung affects the function of the nonischemic lung. Our objective is to determine how apocynin, which is a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, protects the nonischemic control right lung (RL) from injury by the unilateral ischemic left lung (LL). In isolated ventilated (by air containing 5% CO(2)) rat lungs, in which differential perfusion of the RL or LL was feasible, the LL was selectively made ischemic (60 min) and reperfused (30 min) in a nonrecirculating or recirculating manner with buffer (Krebs-Henseleit) solution, or in a recirculating manner with buffer that contained apocynin (10 mmol/L) or apocynin + TACEI (tumor necrosis factor)-alpha converting enzyme inhibitor; 10 microg/mL) (each group: n = 12) or with buffer that contained SOD (superoxide dismutase, 3000 U before ischemia and at reperfusion) or SOD + TACEI (each group: n = 5). The permeability of pulmonary endothelium/epithelium (wet/dry ratio and protein content of bronchoalveolar lavage fluid of each lung), perfusion pressure, and cytokine messenger RNA (mRNA) expression was increased not only in the LL (compared with nonischemic control RL, P < 0.01 with paired-samples T) but also in the RL in recirculating groups (compared with RL in the nonrecirculating group). Apocynin + TACEI as well as SOD + TACEI prevented those permeability increases in the RL by the ischemic LL. However, apocynin with or without TACEI as well as SOD with or without TACEI could only partially ameliorate I/R injury in the LL (P < 0.01 by 1-way analysis of variance (ANOVA)). TNF-alpha and possibly reactive oxygen species produced and released from the ischemic lung may synergistically induce control RL (remote organ) damage.
AuthorsChenting Zhu, Aishan Bilali, Gabriela S Georgieva, Shunichi Kurata, Chieko Mitaka, Takasuke Imai
JournalTranslational research : the journal of laboratory and clinical medicine (Transl Res) Vol. 152 Issue 6 Pg. 273-82 (Dec 2008) ISSN: 1931-5244 [Print] United States
PMID19059162 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Acetophenones
  • Drug Combinations
  • Enzyme Inhibitors
  • Tumor Necrosis Factor-alpha
  • acetovanillone
  • Superoxide Dismutase
  • NADPH Oxidase
  • ADAM Proteins
  • tumor necrosis factor-alpha convertase
Topics
  • ADAM Proteins (antagonists & inhibitors)
  • Acetophenones (pharmacology)
  • Animals
  • Bronchoalveolar Lavage Fluid
  • Cell Membrane Permeability (drug effects, physiology)
  • Disease Models, Animal
  • Drug Combinations
  • Enzyme Inhibitors (pharmacology)
  • Gene Expression (drug effects)
  • Lung (drug effects, metabolism, pathology)
  • Lung Injury (etiology, pathology, prevention & control)
  • Male
  • NADPH Oxidase (antagonists & inhibitors)
  • Permeability
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury (etiology, pathology, prevention & control)
  • Respiratory Mucosa (drug effects, metabolism)
  • Superoxide Dismutase (pharmacology)
  • Tumor Necrosis Factor-alpha (genetics, metabolism)

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