title: Tocopherol supplementation reduces NO production and pulmonary inflammatory response to bleomycin.
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.
authors.affiliation: Department of Respiratory Medicine, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai 200240, China.
authors.forename: Jin Dong
authors.initials: JD
authors.lastname: Shi
authors.forename: Thea
authors.initials: T
authors.lastname: Golden
authors.forename: Chang-Jiang
authors.initials: CJ
authors.lastname: Guo
authors.forename: Shui Ping
authors.initials: SP
authors.lastname: Tu
authors.forename: Pamela
authors.initials: P
authors.lastname: Scott
authors.forename: Mao-Jung
authors.initials: MJ
authors.lastname: Lee
authors.forename: Chung S
authors.initials: CS
authors.lastname: Yang
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Gow
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001761:Bleomycin / Q000633:toxicity*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011014:Pneumonia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012129:Respiratory Function Tests; D024505:Tocopherols / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D001761:Bleomycin; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D024505:Tocopherols
keywords: Lung mechanics; Macrophage activation; Macrophage phenotype; Reactive oxygen and nitrogen species