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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Tocopherol supplementation reduces NO production and pulmonary inflammatory response to bleomycin.

Authors: Shi, Jin Dong; Golden, Thea; Guo, Chang-Jiang; Tu, Shui Ping; Scott, Pamela; Lee, Mao-Jung; Yang, Chung S; Gow, Andrew J

Published In Nitric Oxide, (2013 Nov 01)

Abstract: Bleomycin causes acute lung injury through production of reactive species and initiation of inflammation. Previous work has shown alteration to the production of reactive oxygen species results in attenuation of injury. Vitamin E, in particular, γ-tocopherol, isoform, has the potential to scavenge reactive oxygen and nitrogen species. This study examines the utility of dietary supplementation with tocopherols in reducing bleomycin-mediated acute lung injury. Male C57BL6/J mice were intratracheally instilled with PBS or 2 units/kg bleomycin. Animals were analyzed 3 and 8 days post instillation at the cellular, tissue, and organ levels. Results showed successful delivery of tocopherols to the lung via dietary supplementation. Also, increases in reactive oxygen and nitrogen species due to bleomycin are normalized in those mice fed tocopherol diet. Injury was not prevented but inflammation progression was altered, in particular macrophage activation and function. Inflammatory scores based on histology demonstrate limited progression of inflammation in those mice treated with bleomycin and fed tocopherol diet compared to control diet. Upregulation of enzymes and cytokines involved in pro-inflammation were limited by tocopherol supplementation. Day 3 functional changes in elastance in response to bleomycin are prevented, however, 8 days post injury the effect of the tocopherol diet is lost. The effect of tocopherol supplementation upon the inflammatory process is demonstrated by a shift in the phenotype of macrophage activation. The effect of these changes on resolution and the progression of pulmonary fibrosis has yet to be elucidated.

PubMed ID: 23669183 Exiting the NIEHS site

MeSH Terms: Administration, Oral; Animals; Antioxidants/pharmacology*; Bleomycin/toxicity*; Bronchoalveolar Lavage Fluid/cytology; Cyclooxygenase 2/metabolism; Lung Injury/chemically induced; Lung Injury/drug therapy; Lung Injury/metabolism; Lung Injury/pathology; Lung/drug effects*; Lung/metabolism; Lung/pathology; Male; Mice; Mice, Inbred C57BL; Nitric Oxide Synthase Type II/metabolism; Nitric Oxide/metabolism*; Pneumonia/drug therapy; Pneumonia/metabolism*; Pneumonia/pathology; Reactive Oxygen Species/metabolism; Respiratory Function Tests; Tocopherols/pharmacology*

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