1. Pulmonary injury and oxidative stress in rats induced by inhaled sulfur mustard is ameliorated by anti-tumor necrosis factor-α antibody.
- Author
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Malaviya R, Bellomo A, Abramova E, Croutch CR, Roseman J, Tuttle R, Peters E, Casillas RP, Sunil VR, Laskin JD, and Laskin DL
- Subjects
- Acute Lung Injury metabolism, Animals, Antibodies, Monoclonal pharmacology, Chemical Warfare Agents toxicity, Inhalation Exposure adverse effects, Male, Mustard Gas administration & dosage, Oxidative Stress physiology, Rats, Rats, Wistar, Tumor Necrosis Factor-alpha metabolism, Acute Lung Injury chemically induced, Acute Lung Injury drug therapy, Antibodies, Monoclonal therapeutic use, Mustard Gas toxicity, Oxidative Stress drug effects, Tumor Necrosis Factor-alpha antagonists & inhibitors
- Abstract
Sulfur mustard (SM) is a bifunctional alkylating agent that causes severe injury to the respiratory tract. This is accompanied by an accumulation of macrophages in the lung and the release of the proinflammatory cytokine, tumor necrosis factor (TNF)α. In these studies, we analyzed the effects of blocking TNFα on lung injury, inflammation and oxidative stress induced by inhaled SM. Rats were treated with SM vapor (0.4 mg/kg) or air control by intratracheal inhalation. This was followed 15-30 min later by anti-TNFα antibody (15mg/kg, i.v.) or PBS control. Animals were euthanized 3 days later. Anti-TNFα antibody was found to blunt SM-induced peribronchial edema, perivascular inflammation and alveolar plasma protein and inflammatory cell accumulation in the lung; this was associated with reduced expression of PCNA in histologic sections and decreases in BAL levels of fibrinogen. SM-induced increases in inflammatory proteins including soluble receptor for glycation end products, its ligand, high mobility group box-1, and matrix metalloproteinase-9 were also reduced by anti-TNFα antibody administration, along with increases in numbers of lung macrophages expressing TNFα, cyclooxygenase-2 and inducible nitric oxide synthase. This was correlated with reduced oxidative stress as measured by expression of heme oxygenase-1 and Ym-1. Together, these data suggest that inhibiting TNFα may represent an efficacious approach to mitigating acute lung injury, inflammatory macrophage activation, and oxidative stress induced by inhaled sulfur mustard., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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