OBJECTIVE Cigarette smoke-induced chronic obstructive pulmonary disease(COPD)is a leading cause of death,where inflammation and oxidative stress are involved in the pathogenesis.Vitamin E isoformγ-tocotrienol possesses both anti-oxidative and anti-inflammatory properties.We hypothesized thatγ-tocotrienol may have protective effects against COPD.METHODS BALB/c mice were exposedto cigarette smoke daily for 2 weeks with oralγ-tocotrienol treatment in the second week.Bronchoalveolar lavage(BAL)fluid was assessed for total and differential cell counts,oxidative damage biomarkers,and cytokine levels.Lung tissues were examined for the expression of antioxidants and pro-inflammatory biomarkers.In order to measure changes in lung functions in COPD,another set of mice was exposed to cigarette smoke for 2 months with oralγ-tocotrienol treatment in the last 2 weeks.RESULTSγ-Tocotrienol dose-dependently abated cigarette smoke-induced elevation of BAL fluid total and neutrophil cell counts,cytokine and chemokine(IL-1β,IL-6,IL-17,LIX,G-CSF,KC,RANTES and VEGF)levels,as well as oxidative/nitrosative damage biomarker(advanced oxidation of protein products,8-isoprostane,8-hydroxy-2-deoxyguanosine and 3-nitrotyrosine)levels.γ-Tocotrienol promoted total lung antioxidant capacity and endogenous antioxidant activities of superoxide dismutase,catalase and glutathione peroxidase.More importantly,γ-tocotrienol markedly restored work of breathing and lung functions(total lung capacity,static compliance and FEV100/FVC)in chronic experimental COPD.Furthermore,γ-tocotrienol demonstrated better anti-oxidative,anti-inflammatory,and restoration of lung functions in COPD than prednisolone.CONCLUSION We have shown for the first time the efficacy of vitamin E isomerγ-tocotrienol in protection against cigarette smoke-induced COPD by direct neutralization of free radicals,abating oxidative damage,and restoring antioxidants activities,coupled with anti-inflammatory actions in the inflamed airways. OBJECTIVE Cigarette smoke-induced chronic obstructive pulmonary disease (COPD) is a leading cause of death, where inflammation and oxidative stress are involved in the pathogenesis. Vitamin E isoform γ-tocotrienol possesses both anti-oxidative and anti-inflammatory properties. We hypothesized that γ- tocotrienol may have protective effects against COPD. METHODS BALB / c mice were exposed to cigarette smoke daily for 2 weeks with oral gamma-tocotrienol treatment in the second week. Bronchoalveolar lavage (BAL) fluid was assessed for total and differential cell counts, oxidative damage biomarkers, and cytokine levels. Lung tissues were examined for the expression of antioxidants and pro-inflammatory biomarkers. In order to measure changes in lung functions in COPD, another set of mice was exposed to cigarette smoke for 2 months with oral gamma-tocotrienol treatment in the last 2 weeks. RESULTS γ-Tocotrienol dose-dependently abated cigarette smoke-induced elevation of BAL fluid total and neutrophil cell counts, cyto kine and chemokine levels (IL-1β, IL-6, IL-17, LIX, G-CSF, KC, RANTES and VEGF) levels as well as oxidative / nitrosative damage biomarker (advanced oxidation of protein products, 8-isoprostane, 8 -hydroxy-2-deoxyguanosine and 3-nitrotyrosine levels. γ-Tocotrienol promoted total lung antioxidant capacity and endogenous antioxidant activities of superoxide dismutase, catalase and glutathione peroxidase. Importantly, γ-tocotrienol markedly restored work of breathing and lung functions (total lung capacity, static compliance and FEV100 / FVC) in chronic experimental COPD. Thermore, γ-tocotrienol said: 5: better anti-oxidative, anti-inflammatory, and restoration of lung functions in COPD than prednisolone.CONCLUSION We have shown for the first time the efficacy of vitamin E isomer γ-tocotrienol in protection against cigarette smoke-induced COPD by direct neutralization of free radicals, abating oxidative damage, and restoring antioxidants activities, coupled with anti-inflammatory actions in the inflamed airwa ys.