Misawa M, Nakano E
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
J Toxicol Environ Health. 1993 Jun;39(2):193-205. doi: 10.1080/15287399309531745.
Reactive oxygens are considered to be one of the mediators involved in inflammation. We investigated the constrictive effects of reactive oxygens generated by aerosolized xanthine/xanthine oxidase (XOD) on the airways of anesthetized guinea pigs. Airway resistance was measured with a modified Konzett-Rössler method and expressed as a change in ventilation overflow (VO). Inhalation of xanthine (1.0 M)/XOD (10, 15 U/ml) caused a significant increase in VO. This airway constriction tended to be enhanced by pretreatment with inhaled superoxide dismutase, but was suppressed by inhaled catalase. Inhalation of hydrogen peroxide caused an airway constriction in a concentration-dependent manner (0.1-2.0 M). Xanthine/XOD significantly enhanced the maximal change in VO after inducing airway inflammation by SO2 exposure. The pretreatment with inhalation of xanthine/XOD did not affect the airway constriction induced by inhaled histamine. However, in SO2-exposed guinea pigs, the inhalation of xanthine/XOD significantly increased the sensitivity to histamine. These results indicate that hydrogen peroxide and other reactive oxygen intermediates produced by xanthine/XOD may cause an airway constriction and airway hyperresponsiveness.
活性氧被认为是参与炎症反应的介质之一。我们研究了雾化的黄嘌呤/黄嘌呤氧化酶（XOD）产生的活性氧对麻醉豚鼠气道的收缩作用。采用改良的Konzett-Rössler方法测量气道阻力，并以通气溢出量（VO）的变化表示。吸入黄嘌呤（1.0 M）/XOD（10、15 U/ml）导致VO显著增加。吸入超氧化物歧化酶预处理倾向于增强这种气道收缩，但吸入过氧化氢酶则抑制这种收缩。吸入过氧化氢以浓度依赖的方式（0.1 - 2.0 M）引起气道收缩。黄嘌呤/XOD在通过二氧化硫暴露诱导气道炎症后显著增强了VO的最大变化。吸入黄嘌呤/XOD预处理不影响吸入组胺诱导的气道收缩。然而，在二氧化硫暴露的豚鼠中，吸入黄嘌呤/XOD显著增加了对组胺的敏感性。这些结果表明，过氧化氢和黄嘌呤/XOD产生的其他活性氧中间体可能导致气道收缩和气道高反应性。
