Student Research: Jason Allen

, Occupational and Environmental Medicine (OEM), 2006
Faculty Advisor: Joel D. Kaufman

Oxidative Stress and Antioxidant Status in Controlled Human Diesel Exhaust Exposure: A Randomized, Blinded, Cross-Over Experiment


Abstract

Introduction: Traffic related air pollution is associated with cardiovascular morbidity and mortality. Although the biological mechanisms are not well understood, oxidative stress may be a primary pathway.

Aims: Our objective was to assess the relationship between exposure to diesel exhaust (DE) and indicators of systemic antioxidant and oxidative response in adults with the metabolic syndrome (MeS). We hypothesized that DE exposure would result in greater oxidative stress and antioxidant response compared with FA.

Method: Randomized, double-blind, cross-over experiment in 10 adults with MeS. Subjects received a 2 hr controlled exposure to DE (200μg/m3) or filtered air (FA), randomized to order, followed by a >wk washout period and the cross-over exposure. To assess short-term antioxidant response we analyzed plasma ascorbate (vitamin C), ninety minutes after the start of the exposure. Plasma nitrate + nitrite levels were measured to determine oxidative response, assessed at 22 hrs after exposure initiation. Urinary Isoprostane (8-isoPGF2α), 8-hydroxy-2’ deoxyguanosine (8-OHdG) were used to assess oxidative stress at 22 hrs after exposure initiation. All outcomes were compared to baseline (pre-exposure) levels, and mean changes were calculated and compared between FA and DE exposure.

Results: At 90 minutes after exposure initiation, mean changes in ascorbate (mg/dl) associated with FA (0.92 [95% CI = 0.5, 1.3]) and DE (0.96[0.7, 1.2]) were similar. Changes were also similar in nitrate + nitrite (μmol/L) (4.9 [-1.3, 10.1]). At 22 hrs, mean changes in urinary isoprostane (ng/mg creatinine) (0.53 [-1.97, 0.14]), 8-OHdG (μg/g creatinine) (0.12[0.06, 0.18]) and between DE and FA were also not statistically significant.

Conclusions: In subjects with MeS exposed to 200μg/m3DE, we did not detect significant changes in systemic antioxidant response or oxidative stress, as measured by ascorbate, nitrate + nitrite, 8-isoPGF2α, and 8-OHdG.