Amiodarone Causes Acute Oxidant Lung Injury in Ventilated and Perfused Rabbit Lungs

Tp, Kennedy; Gb, Gordon; Paky, A.; McShane, A. J.; Nf, Adkinson; Sp, Peters; Friday, Karen J.; Jackman, Warren M.; Am, Sciuto; Gh, Gurtner

doi:10.1097/00005344-198807000-00004

Cited by 46 publications

(22 citation statements)

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“…Amiodarone inhibits mitochondrial complex I and II respiration and produces mitochondrial dysfunction in lung epithelial cells and macrophages (19). In the ventilated perfused rabbit lung system, amiodarone increases the levels of ROS and oxidized glutathione (GSSG) (106). Further studies have revealed that amiodarone is metabolized to an aryl radical that may give rise to other ROS (146,208).…”

Section: Fibrogenic Drugs Antioxidants and Oxidative Stressmentioning

confidence: 99%

Antioxidants as Potential Therapeutics for Lung Fibrosis

Day

2008

Antioxidants & Redox Signaling

125

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Interstitial lung disease encompasses a large group of chronic lung disorders associated with excessive tissue remodeling, scarring, and fibrosis. The evidence of a redox imbalance in lung fibrosis is substantial, and the rationale for testing antioxidants as potential new therapeutics for lung fibrosis is appealing. Current animal models of lung fibrosis have clear involvement of ROS in their pathogenesis. New classes of antioxidant agents divided into catalytic antioxidant mimetics and antioxidant scavengers are being developed. The catalytic antioxidant class is based on endogenous antioxidant enzymes and includes the manganese-containing macrocyclics, porphyrins, salens, and the non-metal-containing nitroxides. The antioxidant scavenging class is based on endogenous antioxidant molecules and includes the vitamin E analogues, thiols, lazaroids, and polyphenolic agents. Numerous studies have shown oxidative stress to be associated with many interstitial lung diseases and that these agents are effective in attenuating fibroproliferative responses in the lung of animals and humans.

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Section: Fibrogenic Drugs Antioxidants and Oxidative Stressmentioning

confidence: 99%

Antioxidants as Potential Therapeutics for Lung Fibrosis

Day

2008

Antioxidants & Redox Signaling

125

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“…Rabbits treated with BHA were injected with 100 mg/kg intraperitoneally for 3 d before phosgene exposure. This dose of BHA is similar to that previously shown to prevent oxidant injury in rabbit lungs (17,18). Rabbits treated with ibuprofen were injected with 12.5 mg/kg intravenously after phosgene exposure and 12.5 mg/kg intraperitoneally 2 and 4 h later.…”

Section: Experimental Designmentioning

confidence: 77%

“…To determine if ibuprofen could attenuate lung injury when given after exposure, rabbits were exposed to phosgene, treated immediately afterward with ibuprofen, and then studied 4 h later. In addition, other rabbits were pretreated with the food additive antioxidant butylated hydroxyanisole (BHA)' to determine if oxidant injury from phosgene could be ameliorated by antioxidant therapy (17,18). Injury was assessed by transvascular fluid flux and lung wet/dry weight ratios.…”

Section: Experimental Designmentioning

confidence: 99%

Ibuprofen prevents oxidant lung injury and in vitro lipid peroxidation by chelating iron.

Kennedy¹,

Rao²,

Noah³

et al. 1990

J. Clin. Invest.

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Because ibuprofen protects from septic lung injury, we studied the effect of ibuprofen in oxidant lung injury from phosgene. Lungs from rabbits exposed to 2,000 ppm-min phosgene were perfused with Krebs-Henseleit buffer at 50 ml/min for 60 min. Phosgene caused no increase in lung generation of cyclooxygenase metabolites and no elevation in pulmonary arterial pressure, but markedly increased transvascular fluid flux (A W = 31±5 phosgene vs. 8±1 g unexposed, P < 0.001), permeability to albumin (1251-HSA) lung leak index 0.274±0.035 phosgene vs. 0.019±0.001 unexposed, P < 0.01; 1251-HSA lavage leak index 0.352±0.073 phosgene vs. 0.008±0.001 unexposed, P < 0.01), and lung malondialdehyde (50±7 phosgene vs.24±0.7 gmol/g dry lung unexposed, P < 0.01). Ibuprofen protected lungs from phosgene (A W = 10±2 g; lung leak index 0.095±0.013; lavage leak index 0.052±0.013; and malondialdehyde 16±3 gmol/g dry lung, P < 0.01). Because iron-treated ibuprofen failed to protect, we studied the effect of ibuprofen in several iron-mediated reactions in vitro. Ibuprofen attenuated generation of * OH by a Fenton reaction and peroxidation of arachidonic acid by FeCI3 and ascorbate. Ibuprofen also formed iron chelates that lack the free coordination site required for iron to be reactive. Thus, ibuprofen may prevent iron-mediated generation of oxidants or iron-mediated lipid peroxidation after phosgene exposure. This suggests a new mechanism for ibuprofen's action. (J. Clin. Invest. 1990.

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“…In this regard taurine has been used to protect animals from pulmonary fibrosis induced by the oxidant moieties, i.e., superoxide anion and free radicals, which increase in lung tissue after exposure to paraquat (Gordon et al, 1992), amiodarone (Kennedy et al, 1988), bleomycin (Wang et al, 1989), nitrogen dioxide (Gordon et al, 1986(Gordon et al, , 1992, and ozone (Banks et al, 1990(Banks et al, , 1991(Banks et al, , 1992. Gordon and colleagues (1992) reported that when Golden Syrian hamsters were injected with paraquat or given an intratracheal instillation of bleomycin it could be demonstrated by light microscopy (after glutaraldehyde-cacodylate fixation of the lungs) at one day after treatment, a localized, mild edema, and aggregation of large numbers of inflammatory cells in the lung tissue.…”

Section: Discussionmentioning

confidence: 99%

“…However, while the mechanism of action of the protective ability of taurine is unknown it is presumed that the antioxidant properties of taurine are involved. Paraquat, a broad spectrum herbicide, bleomycin an antineoplastic agent, and amiodarone, an antiarrhythmic agent, produce pulmonary fibrosis possibly by forming superoxides and free radicals in the lung (Hussain et al 1985;Kennedy et al, 1988;Wang et al, 1989;Gordon et al, 1992). Other studies involving taurine as a protecting agent against oxidant injury induced by nitrogen dioxide and ozone in lung tissue have also been reported (Gordon et al, 1986;Banks et al, 1990Banks et al, , 1991Banks et al, , 1992.…”

Section: Introductionmentioning

confidence: 99%

Effects ofin vivo taurine depletion on induced- chemiluminescence production in macrophages isolated from rat lungs

Zhang

Lombardini

1998

Amino Acids

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Alveolar macrophages isolated by pulmonary lavage from partially taurine-depleted rats demonstrated increased (2-2.6 fold) chemiluminescence due to the extracellular reaction between exogenous zymosan and various reactive forms of oxygen compared to macrophages isolated from control animals. Partial taurine depletion was achieved by adding 3% beta-alanine to the drinking water of the rats for 5 weeks prior to harvesting the macrophages. Superoxide dismutase activity was not increased in the lung tissue of the taurine-depleted rats. These data suggest that taurine has antioxidant properties and that taurine depletion is potentially deleterious to alveolar macrophages and pulmonary tissue.

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Amiodarone Causes Acute Oxidant Lung Injury in Ventilated and Perfused Rabbit Lungs

Cited by 46 publications

References 0 publications

Antioxidants as Potential Therapeutics for Lung Fibrosis

Antioxidants as Potential Therapeutics for Lung Fibrosis

Ibuprofen prevents oxidant lung injury and in vitro lipid peroxidation by chelating iron.

Effects ofin vivo taurine depletion on induced- chemiluminescence production in macrophages isolated from rat lungs

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