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Laboratory and Animal Investigations |

Tissue Lipid Peroxidation and Reduced Glutathione Depletion in Hypochlorite-Induced Lung Injury*

Stefan Hammerschmidt, MD; Nicole Büchler; Hans Wahn, MD
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*From the Department of Medicine, University Würzburg, Würzburg, Germany.

Correspondence to: Stefan Hammerschmidt, MD, Medizinische Universitätsklinik I, Johannisallee 32, D-04103 Leipzig, Germany; e-mail: stefan.hammerschmidt@t-online.de



Chest. 2002;121(2):573-581. doi:10.1378/chest.121.2.573
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Study objective: Neutrophils are involved in acute lung injury during ARDS via several mechanisms. This study focuses on neutrophil-derived oxidative stress. Hypochlorite is a major neutrophil-derived oxidant. This study characterizes hypochlorite-induced acute changes in pulmonary circulation and the involvement of tissue lipid peroxidation (LPO) and reduced glutathione (rGSH) depletion.

Methods: Hypochlorite (500, 1,000, and 2,000 nmol/min) or buffer (control) were infused into isolated rabbit lungs. Pulmonary artery pressure (PAP), capillary filtration coefficient (Kf,c) [104/mL/s/cm H2O/g], and lung weight were measured. Experiments were terminated after 105 min or when fluid retention was > 50 g. Lung tissue was frozen immediately after termination of the experiments and analyzed for LPO products and rGSH (nanomoles per milligram of protein).

Results: Baseline PAP and Kf,c values averaged from 6.1 to 6.5 mm Hg and from 0.97 to 1.23, respectively, in all groups. Hypochlorite infusion of 500, 1,000, and 2,000 nmol/min (n = 5 to 7 per group) evoked an increase (mean ± SEM) in maximum PAP (PAPmax) [12.9 ± 2.1, 14.3 ± 1.7, and 13.3 ± 2.2 mm Hg], in maximum Kf,c (Kf,cmax) [1.9 ± 1.2, 6.34 ± 1.2, and >10.0], and in tissue LPO products (1.7 ± 0.06, 2.1 ± 0.06, and 2.3 ± 0.11 vs 1.4 ± 0.04 in controls), and a decrease in tissue rGSH (73.4 ± 8.7, 43.0 ± 9.6, and 50.4 ± 7.2 vs 139 ± 12.6 in controls). Parameters of lung injury (PAPmax and Kf,cmax) of each single experiment were closely correlated with tissue rGSH but did not correlate with tissue LPO products. All changes are significant (p < 0.05) vs control.

Conclusion: The neutrophil-specific oxidant hypochlorite induces acute lung injury, rGSH depletion, and LPO in isolated rabbit lungs. The lung injury correlates with rGSH depletion, suggesting an important mechanistic role in hypochlorite-induced acute lung injury.

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