Effect of the NADPH oxidase inhibitor apocynin on ischemia-reperfusion lung injury

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Abstract

Apocynin (4-hydroxy-3-methoxy-acetophenone) inhibits NADPH oxidase in activated polymorpho-nuclear (PMN) leukocytes, preventing the generation of reactive oxygen species. To determine if apocynin attenuates ischemia-reperfusion lung injury, we examined the effects of apocynin (0.03, 0.3, and 3 mM) in isolated in situ sheep lungs. In diluent-treated lungs, reperfusion with blood (180 min) after 30 min of ischemia (ventilation 28% O2, 5% CO2) caused leukocyte sequestration in the lung and increased vascular permeability [reflection coefficient for albumin (σ(alb)) 0.47 ± 0.10, filtration coefficient (K(f)) 0.14 ± 0.03 g · min-1 · mmHg-1 · 100 g-1] compared with nonreperfused lungs (σ(alb) 0.77 ± 0.03, K(f) 0.03 ± 0.01 g · min-1 · mmHg-1 · 100 g-1; P < 0.05). Apocynin attenuated the increased protein permeability at 0.3 and 3 mM (σ(alb)) 0.69 ± 0.05 and 0.91 ± 0.03, respectively, P < 0.05); K(f) was decreased by 3 mM apocynin (0.05 ± 0.01 g · min-1 · mmHg1 · 100 g-1, P < 0.05). Diphenyleneiodonium (DPI, 5 μM), a structurally unrelated inhibitor of NADPH oxidase, worsened injury (K(f) 0.32 ± 0.07 g · min-1 · mmHg-1 · 100 g-1, P < 0.05). Neither apocynin nor DPI affected leukocyte sequestration. Apocynin and DPI inhibited whole blood chemiluminescence and isolated PMN leukocyte-induced resazurin reduction, confirming NADPH oxidase inhibition. Apocynin inhibited pulmonary artery hypertension and perfusate concentrations of cyclooxygenase metabolites, including thromboxane B2. The cyclooxygenase inhibitor indomethacin had no effect on the increased vascular permeability, suggesting that cyclooxygenase inhibition was not the explanation for the apocynin results. Apocynin prevented ischemia-reperfusion lung injury, but the mechanism of protection remains unclear.

Original languageEnglish (US)
Pages (from-to)H303-H312
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume279
Issue number1 48-1
StatePublished - Aug 23 2000

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Keywords

  • Diphenyleneiodonium
  • Pulmonary edema
  • Sheep
  • Vascular permeability

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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