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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.
ACKNOWLEDGMENTS
This manuscript was supported by National Institute of Health grants NIH K08: KHL089135A, R03:AG037768-01, and AHA grants: 10GRNT3530045 (to TN), HL68111 and ES015482 (to YT) and by the Tobacco Master Settlement through a cooperative research agreement with the University of New Mexico.
| ABBREVIATIONS | ||
| AOD | = | antioxidant diet |
| BALF | = | bronchoalveolar fluid |
| COPD | = | chronic obstructive pulmonary disease |
| CS | = | cigarette smoke |
| FA | = | filtered air |
| HCS | = | high concentration of cigarette smoke |
| LCS | = | low concentration of cigarette smoke |
| MMP | = | metalloproteinase |
| NRF-2 | = | nuclear factor erythroid-derived 2, like 2 |
| RD | = | regular diet |
| SOD | = | superoxide dismutase |
| TBARS | = | thiobarbituric acid-reactive substances |
| TEAC | = | trolox equivalent antioxidant capacity |
| TPM | = | total particulate matter. |