Effects of inducible nitric oxide synthase inhibitors on asthma depending on administration schedule
Effects of inducible nitric oxide synthase inhibitors on asthma depending on administration schedule
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DOI：
10.1016/j.freeradbiomed.2005.10.057
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发表时间：
2006-03-15
影响因子：
7.4
通讯作者：
Tanaka, K
中科院分区：
文献类型：
--
作者：
Abe, M;Hayashi, Y;Tanaka, K
研究了两种诱导型一氧化氮合酶（iNOS）抑制剂在不同给药方案下对过敏性气道炎症的有效性。卵清蛋白（OVA）致敏大鼠连续暴露于OVA 3天。两种iNOS抑制剂在两种预处理时间表之间显示出显著不同的效果：三次OVA暴露中的每一次之前的预处理（SI）和单独第三次暴露之前的预处理（S2）。S1预处理导致比单独的三倍OVA更高的肺阻力。这种增强作用与肺中嗜酸性粒细胞浸润和丙二醛水平增加有关，而超氧化物歧化酶（SODS）可抑制肺中嗜酸性粒细胞浸润和丙二醛水平，但甲基强的松龙不能抑制。然而，两种iNOS抑制剂的S2给药完全抑制了气道反应。给药方案S1完全抑制血浆亚硝酸盐和硝酸盐水平，但S2仅引起轻微抑制。三倍OVA暴露导致肺泡巨噬细胞中的iNOS和呼吸酶活性、Mn-和Cu/Zn-SOD表达以及气道中的硝基酪氨酸和脂质过氧化物沉积的上调。然而，通过时间表S1施用的抑制剂抑制这种上调，但进一步增强硝基酪氨酸，这反过来又被SOD抑制。虽然iNOS抑制剂可能对哮喘有益，但重复给药可能是有害的，因为NO大量减少和SOD下调。(C)2005年爱思唯尔公司All rights reserved.
The effectiveness of two inducible nitric oxide synthase (iNOS) inhibitors oil allergic airway inflammation was investigated under different administration schedules. Rats sensitized to ovalbumin (OVA) were exposed to OVA for 3 consecutive days. Both iNOS inhibitors showed markedly different effects between two pretreatment schedules: pretreatment before each of three OVA exposures (SI) and before the third exposure alone (S2). S1 pretreatment resulted in higher pulmonary resistance than triple OVA alone. This potentiation was associated with increased eosinophil infiltration and malondialdehyde levels in the lungs, which were suppressed by superoxide dismutases (SODS) but not by methylprednisolone. However, the S2 administration of both iNOS inhibitors completely suppressed the airway response. Administration by schedule S1 completely Suppressed plasma nitrite and nitrate levels, but that by S2 caused only a slight suppression. The triple OVA exposures resulted in the upregulation of iNOS in alveolar macrophages and arginase activity, Mn- and Cu/Zn-SOD expression, and nitrotyrosine and lipid peroxide deposition in the airway. However, inhibitors administered by schedule S1 suppressed this upregulation, but further potentiated nitrotyrosine, which in turn was inhibited by SOD. Although iNOS inhibitors may be beneficial for asthma, repeated administration may be detrimental because of extensive reduction of NO and downregulation of SOD. (C) 2005 Elsevier Inc. All rights reserved.