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)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume279
Issue number1 48-1
StatePublished - 2000

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NADPH Oxidase
Lung Injury
Reperfusion Injury
Leukocytes
Albumins
Lung
Capillary Permeability
Prostaglandin-Endoperoxide Synthases
acetovanillone
Thromboxane B2
Cyclooxygenase Inhibitors
Luminescence
Pulmonary Hypertension
Indomethacin
Pulmonary Artery
Reperfusion
Ventilation
Permeability
Reactive Oxygen Species
Sheep

Keywords

  • Diphenyleneiodonium
  • Pulmonary edema
  • Sheep
  • Vascular permeability

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

@article{468af02c0f9a45808ebde4222e33c21c,
title = "Effect of the NADPH oxidase inhibitor apocynin on ischemia-reperfusion lung injury",
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.",
keywords = "Diphenyleneiodonium, Pulmonary edema, Sheep, Vascular permeability",
author = "Dodd-o, {Jeffrey M} and Pearse, {David B}",
year = "2000",
language = "English (US)",
volume = "279",
journal = "American Journal of Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "1 48-1",

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TY - JOUR

T1 - Effect of the NADPH oxidase inhibitor apocynin on ischemia-reperfusion lung injury

AU - Dodd-o, Jeffrey M

AU - Pearse, David B

PY - 2000

Y1 - 2000

N2 - 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.

AB - 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.

KW - Diphenyleneiodonium

KW - Pulmonary edema

KW - Sheep

KW - Vascular permeability

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M3 - Article

VL - 279

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6135

IS - 1 48-1

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