Air pollutants, such as ozone (O3) and diesel exhaust particles, elicit oxidative stress in the lung. Antioxidants within the respiratory tract lining fluid (RTLF) protect the underlying tissue from oxidative injury. Supplementation with vitamins has been shown to modulate the acute ozone-induced effects, but the mechanisms behind this have not been fully clarified. The aim of this thesis was to investigate the airway responses to diesel exhaust and ozone exposure in healthy humans, with the emphasis on inflammatory and antioxidant responses. Furthermore, to study whether oral supplementation with vitamin C could increase ascorbate concentration in the RTLF and whether vitamin supplementation could modulate the negative effects induced by ozone exposure. Diesel exhaust (100 µg/m3 PM10 for 2h), evaluated 18 hours post exposure (PE), induced a neutrophilic airway inflammation and an increase in bronchoalveolar (BAL) urate and reduced glutathione. During O3 exposure (0.2 ppm for 2h), significant losses of nasal RTLF urate and ascorbate concentrations were observed. Six hours PE, a neutrophilic inflammation was evident in the bronchial wash (BW), together with enhanced concentrations of urate and total glutathione. In the bronchoalveolar lavage (BAL), where vitamin C, urate and glutathione concentrations were augmented, no inflammatory response was seen. In alveolar lavage leukocytes, there was a significant loss of glutathione and cysteine, whereas an increase in ascorbate was found in bronchial tissue samples. Following supplementation with increasing doses of vitamin C (60-1,000 mg/day, for 14 days), evaluated 24 hours after the last dose, ascorbate concentrations were unchanged in the nasal RTLF, despite elevated concentrations in plasma and urine. In contrast, following a single dose of 1g of vitamin C, vitamin C concentrations increased significantly in both plasma and nasal lavage two hours post supplementation, before returning to baseline levels at 24 hours. Notably, dehydroascorbate (DHA) accounted for the largest part of RTLF vitamin C and a number of control experiments were performed to ensure the authenticity of this finding. Healthy O3 responders were exposed to O3 (0.2 ppm for 2 h) and air, following seven days of supplementation with vitamin C and E or placebo. No protective effect on lung function or airway inflammation was observed following supplementation. BW and BAL-DHA were enhanced after O3, with further increases following supplementation. In conclusion, oxidative air pollutants induce airway inflammation, as well as a broad spectrum of antioxidant adaptations, which could ultimately limit the airway inflammatory responses. Oral vitamin supplementation was shown to augment RTLF-vitamin C concentrations, but it did not provide protection from the ozone-induced airway responses following a single insult of ozone. The finding of high concentrations of DHA in the RTLF could indicate that DHA represents an important transport form of vitamin C onto the surface of the lung.

Vitamins are readily available in the modern diet due to liberalized fortification and supplementation policies. This research tested the hypothesis that high multi-vitamin intake by Wistar rats during pregnancy leads to the development of obesity and characteristics of the metabolic syndrome in the offspring. Pregnant Wistar rats were fed the AIN-93G diet containing either the recommended (RV) or 10-fold increase (HV) in vitamin content. Pups were weaned to the RV diet (Study 1), an obesogenic liquid diet (Ob, Study 2), low vitamin diets (1/3RV or 1/6RV, Study 3), or a nutrient selection paradigm (NSP) with 10% and 60% casein diets (Study 4). Body weight (BW), food intake (FI), glucose and insulin responses, appetite hormones, abdominal fat pad mass (FPM) and systolic blood pressure (SBP) was measured. Expressions of mRNA for hypothalamic serotonin (5-HT) receptors and proopiomelanocortin (POMC) were measured in Study 4. Males, but not females, born to HV dams had higher post-weaning BW and FI when weaned to the RV or 1/3RV diet, and exhibited components of metabolic syndrome, including higher FPM, hyperglycemia, insulin resistance and elevated SBP compared with those born to RV dams. The Ob diet led to exaggerated weight gain and expressions of components of metabolic syndrome in both sexes born to dams fed the HV diet. Female pups on the 1/6RV diet from HV dams had two-fold higher glucose response and lower insulin response, but no difference in post-weaning BW and daily FI compared to those from RV dams. In contrast to the pups born to HV dams and fed a single diet, those from the HV dams and on the NSP gained less weight and ate less, and had lower hypothalamic mRNA expressions of 5-HT receptors and POMC. In conclusion, high multi-vitamin intake during pregnancy may lead to obesity, and result in a higher risk of developing characteristics of metabolic syndrome in the offspring. However, sex, weaning diet composition, and the presence of diet choice alter the outcomes.

Vitamins are readily available in the modern diet due to liberalized fortification and supplementation policies. This research tested the hypothesis that high multi-vitamin intake by Wistar rats during pregnancy leads to the development of obesity and characteristics of the metabolic syndrome in the offspring. Pregnant Wistar rats were fed the AIN-93G diet containing either the recommended (RV) or 10-fold increase (HV) in vitamin content. Pups were weaned to the RV diet (Study 1), an obesogenic liquid diet (Ob, Study 2), low vitamin diets (1/3RV or 1/6RV, Study 3), or a nutrient selection paradigm (NSP) with 10% and 60% casein diets (Study 4). Body weight (BW), food intake (FI), glucose and insulin responses, appetite hormones, abdominal fat pad mass (FPM) and systolic blood pressure (SBP) was measured. Expressions of mRNA for hypothalamic serotonin (5-HT) receptors and proopiomelanocortin (POMC) were measured in Study 4. Males, but not females, born to HV dams had higher post-weaning BW and FI when weaned to the RV or 1/3RV diet, and exhibited components of metabolic syndrome, including higher FPM, hyperglycemia, insulin resistance and elevated SBP compared with those born to RV dams. The Ob diet led to exaggerated weight gain and expressions of components of metabolic syndrome in both sexes born to dams fed the HV diet. Female pups on the 1/6RV diet from HV dams had two-fold higher glucose response and lower insulin response, but no difference in post-weaning BW and daily FI compared to those from RV dams. In contrast to the pups born to HV dams and fed a single diet, those from the HV dams and on the NSP gained less weight and ate less, and had lower hypothalamic mRNA expressions of 5-HT receptors and POMC. In conclusion, high multi-vitamin intake during pregnancy may lead to obesity, and result in a higher risk of developing characteristics of metabolic syndrome in the offspring. However, sex, weaning diet composition, and the presence of diet choice alter the outcomes.