Ability of γ-tocotrienol to Mitigate Inflammation and Preserve Lung Function in a Model of E-Cigarette Induced Chronic Obstructive Pulmonary Disease

Maureen Meister, Will Conrad, Albert Adhya, Shiying Zhang, Chi In Vong, Xiangming Ji
2020 Current Developments in Nutrition  
Objectives Chronic obstructive pulmonary disease (COPD) remains a leading cause of death and treatment options for this condition remain scant. This study aims to examine the ability of γ-tocotrienol to mitigate disease progression in an animal model of COPD induced by e-cigarettes. We hypothesize that γ-tocotrienol will attenuate inflammation and subsequently slow the progression of e-cigarette induced COPD. Methods Scnn1b-Tg + mice (n = 10/group), were exposed to e-cigarette vapor twice daily
more » ... e vapor twice daily for 10 days in an acute model and daily for eight weeks in a chronic model with or without γ-tocotrienol at a dose of 100 mg/kg/day. Following the treatment, animals underwent pulmonary function testing. Upon sacrifice, bronchoalveolar lavage (BAL) fluid and serum were collected for analysis of cytokine expression through cytokine array. Markers of oxidative stress, inflammation, and fibrosis in the lung were assessed via western blot. Mucus accumulation and structural changes (i.e., emphysema) were measured through Periodic Acid-Schiff and Hematoxylin and Eosin staining, respectively. Collagen deposition were evaluated by Sirius Red staining and Sircol Collagen assay. Cell morphology in BAL fluid was analyzed by Diff staining. Results In the acute model, γ-tocotrienol was evidenced to decrease collagen deposition and mucus accumulation in the bronchioles. Additionally, γ-tocotrienol reduced expression of cytokines C-X3-C motif chemokine ligand (CX3CL) 1 (P = 0.017), interleukin (IL) 4 (P = 0.0038) and T-cell immunoglobulin and mucin domain (TIM) 1 (P = 0.0215). Evidenced by large effect size, pulmonary function tests evidenced the ability of γ-tocotrienol to preserve lung function following 8 weeks of e-cigarette exposure. In addition, macrophage presence in BAL fluid was decreased following in mice supplemented with γ-tocotrienol following e-cigarette exposure. Conclusions Our results show the ability of γ-tocotrienol to attenuate the inflammatory response, and preserve lung function in models of e-cigarette induced COPD. These results indicate potential beneficial effects of γ-tocotrienol as an ancillary treatment in COPD. Funding Sources This work was supported by FAMRI foundation "METABOLIC REPROGRAMMING IN PATIENTS WITH COPD", YCSA 2015.
doi:10.1093/cdn/nzaa045_070 fatcat:m3ckeenykvcv3m7ymcmdijjglu