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.
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Authors | Chenting Zhu, Aishan Bilali, Gabriela S Georgieva, Shunichi Kurata, Chieko Mitaka, Takasuke Imai |
Journal | Translational 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 |
PMID | 19059162
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Acetophenones
- Drug Combinations
- Enzyme Inhibitors
- Tumor Necrosis Factor-alpha
- acetovanillone
- Superoxide Dismutase
- NADPH Oxidases
- ADAM Proteins
- ADAM17 Protein
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Topics |
- ADAM Proteins
(antagonists & inhibitors)
- ADAM17 Protein
- 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 Oxidases
(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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