Oxidant lung injury: Intervention with sulfhydryl reagents

Patterson, Carolyn E.; Butler, J. A. V.; Byrne, Frank D.; Rhodes, Mitchell L.

doi:10.1007/bf02713803

Cited by 43 publications

(20 citation statements)

References 33 publications

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“…Variable results have been reported using vitamins E and C, superoxide dismutase, and sulfhydryl compounds to protect against oxidants (4, 6-9, [15][16][17][18][19][20]. Favorable effects with NAC or cysteamine have been described but several are based on reduced lung wet weights (8,15,21) or pleural fluid volumes (21). We also found significant reductions in lung wet weights and pleural fluid volumes using NAC treatment, despite increased histological damage; these findings suggest that these changes may be a consequence of an osmotic or dehydrating effect of the treatment.…”

Section: Discussionmentioning

confidence: 99%

“…The lowest mnortality was less than half that in the other two groups, it was not a significant difference by a chi-squared test. The mean times of premature death with their ranges were 11 (5)(6)(7)(8)(9)(10)(11)(12)(13)(14) hr, 12 (11)(12)(13) hr, and 14.5 (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21) hr for the saline, NAC, and methylprednisolone groups, respectively.…”

Section: Premature Deathsmentioning

confidence: 99%

“…Several thiol compounds have been shown to protect tissues against oxygen toxicity, either by supporting glutathione biosynthesis or by acting as direct scavengers of reactive electrophilic species via the chemical reactivity of their thiol group (6)(7)(8)(9). Four years ago we began a series of experiments to see whether the clinically available thiol-containing drug N-acetylcysteine (NAC) had a potential role in the prophylaxis and treatment of oxygen and other forms of pulmonary toxicity such as that from acrolein and phosgene inhalation.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, however, there has been increasing evidence of the beneficial effects of NAC in isolated tissue models (9) and even in whole animals. One report suggested it reduced the mortality from 7 days of oxygen breathing (8), and another report alleged a protective action of NAC against hyperbaric oxygen exposure based on reduced increases in lung wet and dry weights (15).…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of N-Acetylcysteine and Methylprednisolone As Therapies for Oxygen and Acrolein-Induced Lung Damage

Critchley¹,

Beeley²,

Clark³

et al. 1990

Environmental Health Perspectives

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Reactive oxidizing species are implicated in the etiology of a range of inhalational pulmonary injuries. Consequently, various free radical scavengers have been tested as potential prophylactic agents. The sulfydryl compound, N-acetylcysteine (NAC) is the only such compound clinically available for use in realistic dosages, and it is well established as an effective antidote for the hepatic and renal toxicity of paracetamol. Another approach in pulmonary injury prophylaxis is methylprednisolone therapy. We evaluated NAC and methylprednisolone in two rat models of inhalational injury: 40-hr exposure to >97% oxygen at 1.1 bar and 15-min exposure to acrolein vapor (210 ppm). For oxygen toxicity, NAC (80 mg) or methylprednisolone (10 mg) were given IP every 2 or 6 hr, respectively. For acrolein, single doses of NAC (1 g/kg) and methylprednisolone (30 mg/kg) were given intravenously 15 min before exposure. In sham-exposed control animals, neither treatment favorably effected mortality, lung wet/dry weight ratios, or pulmonary histology. The increases in lung wet/dry weight ratios, seen with both oxygen and acrolein toxicity were reduced with both treatments. However, with oxygen, NAC therapy was associated with considerably increased mortality and histological changes. Furthermore, IP NAC administration resulted in large volumes of ascitic fluid. With acrolein, IV, NAC had no significant effect on mortality or pulmonary histological damage. Methylprednisolone had no beneficial effects on either the mortality or histological damage observed in either toxicity model. We caution against the ad hoc use of NAC in the management of inhalational pulmonary injury.

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Section: Discussionmentioning

confidence: 99%

Section: Premature Deathsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Evaluation of N-Acetylcysteine and Methylprednisolone As Therapies for Oxygen and Acrolein-Induced Lung Damage

Critchley¹,

Beeley²,

Clark³

et al. 1990

Environmental Health Perspectives

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“…No thiol depletion is seen in rats dosed with paraquat (10), and sulfhydryl pretreatments do not ameliorate lethality (11). However, exogenous GSH protects alveolar Type II cells against loss of viability (12).…”

Section: Introductionmentioning

confidence: 99%

A Novel Lung Slice System with Compromised Antioxidant Defenses

Hardwick¹,

Adam²,

Smith³

et al. 1990

Environmental Health Perspectives

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In order to facilitate the study ofoxidative stress in lung tissue, rat lung slices with impaired antioxidant defenses were prepared and used. Incubation of lung slices with the antineoplastic agent 1,3-bis(2-chloroethyl)-1-nitrosourea(BCNU) (100 M) Inanaminoacid-rich mediumfor 45 minproduced a near-maximal (approximately 85 %), irreversible inhibition of glutathione reductase, accompanied by only a modest (approximately 15 %) decrease in pulmonary nonprotein sulfhydryls (NPSH) and no alteration in intracellular ATP, NADPI, and NADPH levels. The amounts of NADP(H), ATP, and NPSH were stable over a 4-hr incubation period following the removal from BCNU. The viability of the system was further evaluated by measuring the rate of evolution of "4CO2 from D-[4C(UJ)-glucose. The rates ofevolution were almost identical in the compromised system when compared with control slices over a 4-hr time period. By using slices with compromised oxidative defenses, preliminary results have been obtained with paraquat, nitrofurantoin, and 2,3-dimethoxy-1,4-naphthoquinone.

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