No Beneficial Effect of N-acetylcysteine Treatment on Broncho-alveolar Lavage Fluid Variables in Acute Nitrogen Dioxide Intoxicated Rats

Meulenbelt, Jan; Bree, L. van; Dormans, J. A. M. A.; Sangster, B.

doi:10.1177/096032719401300704

Cited by 3 publications

(1 citation statement)

References 15 publications

(3 reference statements)

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“…Evidence for a beneficial effect of NAC administration on lung injury was also obtained from experimental hyperoxia studies [22]. However, the results concerning lavage protein are in contrast to another study also using NO 2 as oxidant that did not find an influence of NAC on this lavage parameter [35].…”

Section: Discussionmentioning

confidence: 99%

Effect of N‐acetylcysteine treatment on NO₂‐impaired type II pneumocyte surfactant metabolism

Müller

Oske

Hochscheid

et al. 2001

Eur J Clin Investigation

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Inhalation of nitrogen dioxide (NO2) is known to alter the composition of the bronchoalveolar lavage (BAL) and to impair the surfactant metabolism of type II pneumocytes. However, information is sparse as to whether application of the widely used antioxidant N-acetylcysteine (NAC) is capable of preventing or reducing these alterations. The aim of the study was to investigate if in vivo administration of NAC to NO2-inhaling rats protected BAL parameters and physiology of type II pneumocytes from impairment. For this purpose, rats were exposed to 720 p.p.m. h-1 NO2, that was applied continuously, intermittently or repeatedly. During inhalation one group of rats received saline and the other group received NAC antioxidant (200 mg kg-1, intraperitoneally) once a day. The BAL protein and phospholipid content increased most in the continuously and repeatedly NO2-exposed rats when compared to the controls, while the intermittent exposure did not change these parameters. Application of NAC led to a marked decrease of the protein elevation for the continuously and intermittently exposed groups, but exhibited no influence on the BAL phospholipid. Surprisingly, all NO2 exposure modes elevated the glutathione content (reduced and oxidized) in the BAL. Application of NAC clearly decreased the content of both forms of glutathione in the continuously and the repeatedly NO2-exposed groups. Phospholipid synthesis, measured by choline uptake into type II cells, was increased most after continuous NO2 inhalation. The NAC reduced this increase moderately. Whereas choline uptake by type II cells was obviously stimulated by NO2, the stimulated secretion of phosphatidylcholine from these cells was decreased by this oxidant. Only continuous exposure reduced this activity markedly. The NAC clearly restored the impaired secretion activity in the cells from the continuously NO2-exposed animals. Since the efficacy of NAC in the prevention of NO2-induced impairments in the surfactant system is striking mainly in the continuously exposed group, we suggest that administration of NAC to NO2-induced lung injury partially restores altered BAL components and the impaired physiology of type II pneumocytes.

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Section: Discussionmentioning

confidence: 99%

Effect of N‐acetylcysteine treatment on NO₂‐impaired type II pneumocyte surfactant metabolism

Müller

Oske

Hochscheid

et al. 2001

Eur J Clin Investigation

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N-Acetylcystei ne: Pharmacological Considerations and Experimental and Clinical Applications

Cotgreave

1996

Advances in Pharmacology

392

291

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Antioxidant Depletion, Lipid Peroxidation, and Impairment of Calcium Transport Induced by Air-Blast Overpressure in Rat Lungs

Elsayed

Tyurina

Tyurin

et al. 1996

Experimental Lung Research

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Exposure to blast overpressure, or the sudden rise in atmospheric pressure after explosive detonation, results in damage mainly of the gas-filled organs. In addition to the physical damage, in the lung, injury may proceed via a hemorrhage-dependent mechanism initiating oxidative stress and accumulation of lipid peroxidation products. Massive rupture of capillaries and red blood cells, release of hemoglobin, its oxidation to met-hemoglobin and degradation sets the stage for heme-catalyzed oxidations. The authors hypothesized that lipid hydroperoxides interact with met-hemoglobin in the lungs of exposed animals to produce ferryl-hemoglobin, an extremely potent oxidant that induces oxidative damage by depleting antioxidants and initiating peroxidation reactions. Oxidation-induced disturbance of Ca2+ homeostasis facilitates further amplification of the damage. To test this hypothesis, groups of anesthetized rats (6 rats/group) were exposed to blast at 3 peak pressures: low (61.2 kPa), medium (95.2 kPa), high (136 kPa). One group served as an unexposed control. Immediately after exposure, the rats were euthanized and the lungs were analyzed for biochemical parameters. Blast overpressure caused: (1) depletion of total and water-soluble pulmonary antioxidant reserves and individual antioxidants (ascorbate, vitamin E, GSH), (2) accumulation of lipid peroxidation products (conjugated dienes, TBARS), and (3) inhibition of ATP-dependent Ca2+ transport. The magnitude of these changes in the lungs was proportional to the peak blast overpressure. Inhibition of Ca2+ transport strongly correlated with both depletion of antioxidants and enhancement of lipid peroxidation. In model experiments, met-hemoglobin/H2O2 produced damage to Ca2+ transport in the lungs from control animals similar to that observed in the lungs from blast overpressure-exposed animals. Ascorbate, which is known to reduce ferryl-hemoglobin, protected against met-hemoglobin/H2O2-induced damage of Ca2+ transport. If ferryl-hemoglobin is the major reactive oxygen species released by hemorrhage, then its specific reductants (e.g., nitric oxide) along with other antioxidants may be beneficial protectants against pulmonary barotrauma.

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No Beneficial Effect of N-acetylcysteine Treatment on Broncho-alveolar Lavage Fluid Variables in Acute Nitrogen Dioxide Intoxicated Rats

Cited by 3 publications

References 15 publications

Effect of N‐acetylcysteine treatment on NO₂‐impaired type II pneumocyte surfactant metabolism

Effect of N‐acetylcysteine treatment on NO₂‐impaired type II pneumocyte surfactant metabolism

N-Acetylcystei ne: Pharmacological Considerations and Experimental and Clinical Applications

Antioxidant Depletion, Lipid Peroxidation, and Impairment of Calcium Transport Induced by Air-Blast Overpressure in Rat Lungs

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No Beneficial Effect of N-acetylcysteine Treatment on Broncho-alveolar Lavage Fluid Variables in Acute Nitrogen Dioxide Intoxicated Rats

Cited by 3 publications

References 15 publications

Effect of N‐acetylcysteine treatment on NO2‐impaired type II pneumocyte surfactant metabolism

Effect of N‐acetylcysteine treatment on NO2‐impaired type II pneumocyte surfactant metabolism

N-Acetylcystei ne: Pharmacological Considerations and Experimental and Clinical Applications

Antioxidant Depletion, Lipid Peroxidation, and Impairment of Calcium Transport Induced by Air-Blast Overpressure in Rat Lungs

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Product

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Effect of N‐acetylcysteine treatment on NO₂‐impaired type II pneumocyte surfactant metabolism

Effect of N‐acetylcysteine treatment on NO₂‐impaired type II pneumocyte surfactant metabolism