γ-Tocopherol as a mechanism to inhibit acute and chronic pulmonary inflammation: Structural and functional consequences

Abstract

Pulmonary injury, resulting in acute or chronic inflammation, leads to structural and functional changes. γ -tocopherol, is a potent antioxidant that can react with higher oxides of NO. We studied the effects of γ -tocopherol in both acute (administration of intratracheal bleomycin, ITB) and chronic (Surfactant Protein D knockout, SP-D −/− ) lung inflammation in mice fed a 0.3% γ -tocopherol mixture diet ( γ -TmT). ITB-treated mice were fed γ -TmT 2 weeks prior and through out study, while SP-D −/− mice were fed the diet from 4 weeks of age. ITB caused pulmonary inflammation as seen in increased cell number, protein levels and IHC and rt-PCR markers. γ -TmT reduced these effects. NO 2 - and NO 3 - within the lung lavage were elevated by ITB but normalized by γ -TmT. Pulmonary elastance and resistance were increased due to ITB and elastance was normalized by γ -TmT at 3 days post injury but not 8 days. SP-D −/− mice demonstrate increased inflammation as seen by H&E, cell count, protein levels and IHC and rt-PCR markers and was reduced by γ -TmT. NO 2 - and NO 3 - are increased but normalized by γ -TmT. Despite resolution of inflammatory process, lung function was not resolved. Acute inflammation leads to functional changes that can be improved by γ -TmT. However, chronic inflammation in SP-D −/− produces impairment in both structure and function, which cannot be alleviated by γ -TmT reduction of inflammation. Therefore, γ -TmT plays a valuable role in inhibiting inflammation, particularly during the acute phase, but does not reverse long-term sequelae of inflammation.