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Biochemical changes in lung lavage fluid and alteration in macrophage function in rats exposed to hyperoxia.

Dedhia HV; Castranova V; Ma JYC; Dalal NS; Banks D; Ma JKH; Flink EB; Vallyathan V; Billie M
Am Rev Respir Dis 1992 Apr; 145(4)(Pt 2)(Meeting Abstracts):A608
The aim of this study was to characterize selected pulmonary changes by analyzing lung lavage fluid and pulmonary macrophage (AM) functions in rats exposed to hyperoxia (FiO2 >.95) for 64 hrs (a model of ARDS). A total of 18 Sprague Dawley rats were exposed and 14 served as controls. After sacrifice, bronchoalveolar lavage fluid was analyzed for total and differential cell counts (N = 32), protein and phospholipid content (N = 13), cellular viability (N = 7), lipid peroxidation (LP, N = 8), and glutathione levels (N = 8). AM function (N = 13) was assessed by Chemiluminescence (CL), hydrogen peroxide (H2O2) production (N = 9), and hydroxyl radical (OH) formation (N = 7) measured by electron spin resonance. Cell spreading, (N = 10) was measured by scanning electron microscopy. Hyperoxia did not affect AM spreading, phospholipid content of lavage fluid, or glutathione content of lavaged cells. However, statistically significant changes (p < 0.05), were seen in hyperoxic vs air control rats: elevated protein content (1.67 vs 0.29 mg/ml); increased PMN (1.43 vs 0.76 x 10(6) cell/rat), lymphocyte (1.86 vs 0.33 x 10(6) cell/rat), and RBC (3.75 vs 0.93 x 10(6) cell/rat); reduction in AM (4.84 vs 12.7 x 10(6) cell/rat) counts; and increased LP (2.2 times control). The total cell count and AM viability were reduced from 15.7 to 12.2 x 10(6) cell/rat and 90 to 80% respectively in the hyperoxic rats but were not statistically significant. Zymosan stimulated H2O2 (N = 9) release and OH radical production were decreased 41% and 53% respectively, after hyperoxia. In contrast, zymosan stimulated CL was elevated by 540% in hyperoxic AM. The CL generated by AM from oxygen exposed and control animals showed no significant difference in inhibition by superoxide dismutase (↓O2(-)), indomethacin (↓cyclooxygenase), catalase (↓H2O2) or A 63162 (↓lipoxygenase). We conclude that hyperoxic treatment of rats for 64 hr results in increased lipid peroxidation, alveolar hemorrhage, abnormal capillary permeability and decreased membrane integrity of pulmonary cells. The ability of phagocytes to produce H2O2 and hydroxyl radicals was impaired after 64 hr of hyperoxia: The data indicate that high CL in hyperoxic alveolar macrophages may be due to reactive lipid peroxidation products generated by oxygen exposure.
Respiratory-system-disorders; Pulmonary-system-disorders; Lung-disorders; Lung-function; Airway-obstruction; Airway-resistance; Bronchial-asthma; Pulmonary-function-tests; Measurement-equipment; Workers; Circadian-rhythms; Analytical-instruments; Analytical-processes
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American Review of Respiratory Disease
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Center to Protect Workers' Rights
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