Antioxidant diet protects against emphysema, but increases mortality in cigarette smoke-exposed mice

COPD. 2011 Oct;8(5):362-8. doi: 10.3109/15412555.2011.600361. Epub 2011 Aug 11.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / administration & dosage*
  • Antioxidants / analysis
  • Bronchoalveolar Lavage Fluid / chemistry*
  • Bronchoalveolar Lavage Fluid / cytology
  • Cell Count
  • Diet
  • Enzyme Precursors / analysis
  • Female
  • Fruit
  • Gelatinases / analysis
  • Kaplan-Meier Estimate
  • Lymphocytes
  • Macrophages, Alveolar
  • Matrix Metalloproteinase 2 / analysis
  • Matrix Metalloproteinase 9 / analysis
  • Mice
  • Mice, Inbred C3H
  • Nasal Obstruction / etiology
  • Neutrophils
  • Nicotiana
  • Oxidative Stress
  • Pulmonary Emphysema / pathology
  • Pulmonary Emphysema / prevention & control*
  • Smoke / adverse effects*
  • Vegetables

Substances

  • Antioxidants
  • Enzyme Precursors
  • Smoke
  • Gelatinases
  • progelatinase
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9