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 an antioxidant 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: 250mg/m3) for 6 hours/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.

Xeroderma Pigmentosum Group C Deficiency Alters Cigarette Smoke DNA Damage Cell Fate and Accelerates Emphysema Development

“…Inflammation, apoptosis, and increased emphysema development are observed in mice with inactivation of superoxide dismutase in several different emphysema models (CS, ceramide, and elastase), with these effects attenuated with the addition of superoxide dismutase (39)(40)(41). However, countering this effect may be more complicated than simply limiting oxidative stress, as antioxidant diet was associated with decreased emphysema, but increased mortality in a mouse model of chronic CS exposure (42). It should be noted that the impact of CS and oxidative stress is not limited to alveolar epithelial cells, and similar effects have been observed in lung endothelial cells (43), which play a significant role in emphysema development as well.…”

Cigarette smoke exposure enhances transforming acidic coiled-coil–containing protein 2 turnover and thereby promotes emphysema

“…The lungs of mice were fixed under a constant pressure (25 cm H 2 O) in 10% neutral buffered formalin (Thermo Fisher Scientific, catalog 245684)for 2 hours. After fixation for 24 hours in formalin, lungs were embedded in paraffin and sectioned at 3-μm thickness as previously described (41). Using Scion Image software (Version 4.0.2), mean alveolar CL was measured on 10 randomly selected 200× fields per slide as previously described (40).…”

Oxidative stress and free radicals in COPD – implications and relevance for treatment

“… 120 So there are rational causes for vitamin D supplementation to prevent as well as to treat COPD. Vitamin E supplementation may decrease carbonyl and MDA levels in smokers and in mice with emphysema, 121 and the risk for COPD by up to 10%. 122 A positive association between intake of vitamin E and lung function was reported in a study population of 2,633 individuals.…”