ascorbic-acid and Bronchial-Hyperreactivity

Ozone is an environmentally reactive oxidant, and pycnogenol is a mixture of flavonoid compounds extracted from pine tree bark that have antioxidant activity. We investigated the effects of pycnogenol on reactive nitrogen species, antioxidant responses, and airway responsiveness in BALB/c mice exposed to ozone.. Antioxidant levels were determined using high performance liquid chromatography with electrochemical detection. Nitric oxide (NO) metabolites in bronchoalveolar lavage (BAL) fluid from BALB/c mice in filtered air and 2 ppm ozone with pycnogenol pretreatment before ozone exposure (n = 6) were quantified colorimetrically using the Griess reaction.. Uric acid and ascorbic acid concentrations were significantly higher in BAL fluid following pretreatment with pycnogenol, whereas γ-tocopherol concentrations were higher in the ozone exposed group but were similar in the ozone and pycnogenol pretreatment groups. Retinol and γ-tocopherol concentrations tended to increase in the ozone exposure group but were similar in the ozone and pycnogenol pretreatment groups following ozone exposure. Malonylaldehyde concentrations increased in the ozone exposure group but were similar in the ozone and pycnogenol plus ozone groups. The nitrite and total NO metabolite concentrations in BAL fluid, which parallel the in vivo generation of NO in the airways, were significantly greater in the ozone exposed group than the group exposed to filtered air, but decreased with pycnogenol pretreatment.. Pycnogenol may increase levels of antioxidant enzymes and decrease levels of nitrogen species, suggesting that antioxidants minimize the effects of acute ozone exposure via a protective mechanism.

Topics: alpha-Tocopherol; Animals; Antioxidants; Ascorbic Acid; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Bronchoconstriction; Disease Models, Animal; Female; Flavonoids; Inhalation Exposure; Lung; Malondialdehyde; Mice; Mice, Inbred BALB C; Nitric Oxide; Oxidative Stress; Ozone; Plant Extracts; Uric Acid; Vitamin A

The most important pathological feature of asthma is airway inflammation, which results in airway hyper-responsiveness. We hypothesized that excessive oxidation is likely to contribute to airway inflammation in asthma. The aim of this study was to evaluate the effects of both acute exposure and a 30-day administration of ascorbic acid (AA), which has an antioxidant effect, on airway responsiveness in sensitized guinea pigs.. Guinea pigs sensitized to ovalbumin (OA), were given drinking water without AA (group 2) or with AA (group 3). The responses of tracheal chains of control animals (group 1) and both groups of sensitized guinea pigs (n = 10, for all groups) to cumulative concentrations of methacholine were measured, and the effective concentrations of methacholine causing 50% of maximum response (EC50 M) were obtained. The response of tracheal chains to 0.1% OA, relative to contraction obtained with 10 micro mol/L methacholine, was also measured. The tracheal responses to methacholine and OA were measured on tissues both incubated and not incubated with AA.. The tracheal responses of group 2 tissues were significantly greater than those of groups 1 and 3 to both OA and methacholine (P < 0.05). There were no significant differences in tracheal responses to OA and methacholine between groups 1 and 3. Acute incubation of tissues caused a reduction of tracheal response to methacholine in all groups, but this was only significantly differ-ent for group 3 (P < 0.05). Acute incubation of tissues did not change tracheal response to OA significantly.. These results showed that although short-term administration of AA had no major effect on tracheal responsiveness among sensitized animals, 30-day administration of AA could lead to a decrease in airway responsiveness of sensitized guinea pigs to both OA and methacholine.

Topics: Analysis of Variance; Animals; Antioxidants; Ascorbic Acid; Asthma; Bronchial Hyperreactivity; Drug Administration Schedule; Guinea Pigs; Male; Methacholine Chloride; Ovalbumin; Trachea

The effect of ozone (3 ppm, 15-120 min) on bronchial reactivity in the guinea-pig was studied. Ozone induced marked (6-250-fold) bronchial hyperreactivity (BHR) to a range of inhaled, but not intravenous bronchoconstrictors. The degree of BHR was related to the duration of prior ozone exposure. The glutathione redox status was shifted to a more oxidized state in lung after 120 min ozone treatment, although no changes were found in the energy status of lung tissue, as judged by the concentrations of adenosine phosphates. Ascorbic acid pretreatment prevented BHR induced by 30 min ozone exposure. Neutral endopeptidase inhibitors elicited BHR to both substance P and histamine, but did not further enhance bronchoconstriction to substance P after ozone exposure for 120 min. Neither mepyramine, fentanyl, indomethacin nor a 5-lipoxygenase inhibitor (BW B70C), given prior to ozone exposure prevented the induction of BHR to histamine. Atropine or bilateral vagotomy reduced BHR after a 120-min, but not 30-min exposure to ozone. We conclude that in the guinea-pig, ozone induces non-specific, route-dependent BHR by oxidative injury, reducing airway NEP activity and enhancing the cholinergic and peptidergic component to bronchoconstriction. Neither cyclooxygenase nor 5-lipoxygenase products appear to play a role in ozone-induced BHR in this animal model.

Topics: Adenine Nucleotides; Animals; Ascorbic Acid; Atropine; Bronchial Hyperreactivity; Bronchoconstriction; Disease Models, Animal; Fentanyl; Glutathione; Guinea Pigs; Histamine; Indomethacin; Lipoxygenase Inhibitors; Male; Neprilysin; Oligopeptides; Oxidation-Reduction; Ozone; Pyrilamine; Substance P; Vagus Nerve