Ambroxol reduces LPS toxicity mediated by induction of alkaline phosphatases in rat lung
Ambroxol reduces LPS toxicity mediated by induction of alkaline phosphatases in rat lung
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DOI：
10.1016/j.clinbiochem.2004.02.004
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发表时间：
2004-08-01
影响因子：
2.8
通讯作者：
Komoda, T
中科院分区：
文献类型：
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作者：
Koyama, I;Matsunaga, T;Komoda, T
碱性磷酸酶（APs）被认为通过去磷酸化来解毒脂多糖（LPS）。氨溴索是一种支气管祛痰药，其药理作用是加速肺表面活性物质颗粒（包括AP分子）的分泌。本研究探讨了氨溴索对大鼠肺LPS毒性的一些有益作用。在大鼠肺器官培养实验中，25 PM氨溴索在组织和培养基中孵育后，AP活性呈时间依赖性增强。Western blot分析表明，氨溴索通过诱导表面活性剂蛋白（SPs）和AP分子，提高了AP活性。在体内实验中，大鼠经气管灌注LPS 20 mg/kg后，血清LPS含量明显升高。然而，在LPS攻毒前1 h口服氨溴索（1.0 mg/ kg）预处理大鼠，血清LPS浓度-时间曲线下面积（AUC）明显降低。这些结果表明，氨溴索抑制LPS从肺部转位进入循环，并通过提高AP活性来抑制其解毒作用。溴溴辛，另一种祛痰剂，作为脂多糖解毒剂的效果不如氨溴索。在肺中维持高AP活性水平表明APs对LPS诱导的炎症事件具有显著的生理作用。(C) 2004加拿大临床化学学会。版权所有。
Alkaline phosphatases (APs) have been suggested to detoxify lipopolysaccharide (LPS) by dephosphorylation. Ambroxol, a bronchial expectorant, is known to accelerate the secretion of pulmonary surfactant particles including AP molecules as a pharmacological action. In the present study, some beneficial effects of ambroxol on LPS toxicity in the rat lung were investigated.In an experiment using the rat lung organ culture, AP activities were enhanced in a time-dependent manner by incubation with 25 PM of ambroxol in both the tissue and the medium. Western blot analysis indicated that AP activity was elevated by the treatment with ambroxol, due to the induction of surfactant proteins (SPs) and AP molecules. In the in vivo experiment, the serum LPS content was markedly increased after LPS administration to rats by intratracheal instillation of 20 mg/kg. However, when the rats were pretreated with oral ambroxol (1.0 mg/ kg) at 1 h before LPS challenge, the area under the concentration-time curve (AUC) of serum LPS was significantly decreased. These results suggest that ambroxol inhibits the translocation of LPS from the lung into the circulation as well as its detoxification effect via the elevation of AP activity. Bromhexine, another expectorant, is less effective than ambroxol as an LPS detoxificant. Maintenance of high AP activity level in the lung suggests APs to have physiological significant effects against the inflammatory events induced by LPS. (C) 2004 The Canadian Society of Clinical Chemists. All rights reserved.