Fenech A G, Ellul-Micallef R
Department of Clinical Pharmacology and Therapeutics, University of Malta, Msida.
Pulm Pharmacol Ther. 1998;11(4):301-8. doi: 10.1006/pupt.1998.0122.
Oxidative processes, mediated by free radical chemistry, are recognized to contribute significantly to the inflammatory pathology of bronchial asthma. This study analysed the degree of defence against reactive oxygen species in Maltese, asthmatic patients and in normal individuals, by measuring plasma selenium concentration, erythrocyte glutathione peroxidase (GSH-Px) activity and erythrocyte superoxide dismutase (SOD) activity, in order to determine their antioxidant status. The effect of glucocorticoids on the status of these antioxidants in patients was also investigated. The measurement of antioxidant status was carried out both in mild (n = 22) and severe (n = 37) asthmatics, as well as in healthy controls (n = 49). The same antioxidant profile was then investigated in a group of 16 severe asthmatics following treatment for 4 weeks with inhaled beclomethasone dipropionate (750 micrograms twice daily), and in a second group of 16 patients suffering from severe asthma, following 2-weeks treatment with oral prednisolone (15 mg daily during the first week and 10 mg daily during the second). No statistically significant difference was found in the plasma selenium concentrations and erythrocyte glutathione peroxidase activities between patients and controls. Both mild and severe asthmatics, however, exhibited a statistically significant lower erythrocyte superoxide dismutase activity than normal subjects (mild asthmatics: 62.9 (2.9) SOD 525 U/ml, severe asthmatics: 60.6 (1.9) SOD 525 U/ml, normal: 68.5 (1.1) SOD 525 U/ml, P < 0.01). Inhaled beclomethasone dipropionate exerted no effect on this antioxidant profile, while prednisolone caused a significant increase in plasma selenium concentration over pretreatment values (pretreatment: 118.3 (4.4) ng/ml, post-treatment: 138.1 (4.6 ng/ml, P < 0.01). It is thus suggested that asthmatic patients in Malta might be more susceptible to superoxide-induced damage than normal individuals. The reason for the prednisolone-induced augmentation of plasma selenium could not be determined from this study. It is postulated that the drug may decrease the excretion rate of the element, and may thus exert a positive antioxidant effect in individuals of established low selenium status.
由自由基化学介导的氧化过程被认为对支气管哮喘的炎症病理有显著影响。本研究通过测量血浆硒浓度、红细胞谷胱甘肽过氧化物酶（GSH-Px）活性和红细胞超氧化物歧化酶（SOD）活性，分析了马耳他哮喘患者和正常个体对活性氧的防御程度，以确定他们的抗氧化状态。还研究了糖皮质激素对患者这些抗氧化剂状态的影响。对轻度（n = 22）和重度（n = 37）哮喘患者以及健康对照者（n = 49）进行了抗氧化状态的测量。然后在一组16名重度哮喘患者中进行了相同的抗氧化谱研究，这些患者接受吸入丙酸倍氯米松治疗4周（每日两次，每次750微克），在另一组16名重度哮喘患者中进行了研究，这些患者接受口服泼尼松龙治疗2周（第一周每日15毫克，第二周每日10毫克）。患者和对照者之间的血浆硒浓度和红细胞谷胱甘肽过氧化物酶活性没有发现统计学上的显著差异。然而，轻度和重度哮喘患者的红细胞超氧化物歧化酶活性均显著低于正常受试者（轻度哮喘患者：62.9（2.9）SOD 525 U/ml，重度哮喘患者：60.6（1.9）SOD 525 U/ml，正常：68.5（1.1）SOD 525 U/ml，P < 0.01）。吸入丙酸倍氯米松对这种抗氧化谱没有影响，而泼尼松龙导致血浆硒浓度比治疗前值显著增加（治疗前：118.3（4.4）ng/ml，治疗后：138.1（4.6 ng/ml，P < 0.01）。因此，提示马耳他的哮喘患者可能比正常个体更容易受到超氧化物诱导的损伤。本研究无法确定泼尼松龙诱导血浆硒增加的原因。据推测，该药物可能会降低元素的排泄率，从而可能对已确定为低硒状态的个体发挥积极的抗氧化作用。
