title: Antioxidant diet protects against emphysema, but increases mortality in cigarette smoke-exposed mice.
abstract: Oxidative stress plays an important role in cigarette smoke-induced lung inflammation and emphysema. We produced an enriched diet by adding freeze-dried fruits and vegetables and additional supplements to the 8604 Teklad Rodent Diet, a standard rodent diet. In this study, we examined the effects of the antioxidant-enriched diet on cigarette smoke-induced lung inflammation and emphysema. CH3/HeN mice were fed either a regular diet or the supplemented diet. These mice were exposed to filtered air, a low concentration of cigarette smoke (total particulate matter: 100 mg/m3) or a high concentration of cigarette smoke (total particulate matter: 250 mg/m3) for 6 h/day, 5 days/week for total 16 weeks. Surprisingly, increased mortality (53%) was observed in the high concentration of cigarette smoke-exposed mice fed the antioxidant diet compared to the high concentration of cigarette smoke-exposed mice that were fed a regular diet (13%). The necropsy analysis revealed nasal passage obstruction due to mucous plugging in cigarette smoke-exposed mice on the antioxidant diet. However, the antioxidant diet significantly reduced neutrophilic inflammation and emphysema in the high concentration of cigarette smoke-exposed mice as compared to the regular diet /high concentration of cigarette smoke controls. The antioxidant capacity in the bronchoalveolar fluid or oxidative damage to the lung tissue was not affected by the antioxidant diet. Pro-MMP-2, MMP-2, and MMP-9 activity did not correlate with the protective effects of AOD on cigarette smoke-induced emphysema. These data suggest that the antioxidant diet reduced cigarette smoke-induced inflammation and emphysema, but increased mortality in the obligate nose-breathing mice.
authors.affiliation: Chronic Obstructive Pulmonary Disease Program, Lovelace Respiratory Research Institute, Albuquerque, NM 87108, USA.
authors.forename: Toru
authors.initials: T
authors.lastname: Nyunoya
authors.forename: Thomas H
authors.initials: TH
authors.lastname: March
authors.forename: Yohannes
authors.initials: Y
authors.lastname: Tesfaigzi
authors.forename: JeanClare
authors.initials: J
authors.lastname: Seagrave
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000166:cytology; D002452:Cell Count; D004032:Diet; D004792:Enzyme Precursors / Q000032:analysis; D005260:Female; D005638:Fruit; D018093:Gelatinases / Q000032:analysis; D053208:Kaplan-Meier Estimate; D008214:Lymphocytes; D016676:Macrophages, Alveolar; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D051379:Mice; D008809:Mice, Inbred C3H; D015508:Nasal Obstruction / Q000209:etiology; D009504:Neutrophils; D018384:Oxidative Stress; D011656:Pulmonary Emphysema / Q000473:pathology / Q000517:prevention & control*; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana; D014675:Vegetables
chemical_list: D000975:Antioxidants; D004792:Enzyme Precursors; D012906:Smoke; D018093:Gelatinases; C069860:progelatinase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9