Stetinová V, Herout V, Kvetina J
Institute of Experimental Biopharmaceutics, Joint Research Center of the Academy of Sciences of the Czech Republic and PRO.MED.CS Praha a.s., Heyrovského 1207, 500 03 Hradec Králové, Czech Republic.
Clin Exp Med. 2004 Dec;4(3):152-8. doi: 10.1007/s10238-004-0050-3.
In addition to a mucolytic action, ambroxol has antioxidant and anti-inflammatory properties. The antioxidant effects of ambroxol were studied both in vitro and in vivo. In vitro methods, such as (1) inhibition of hyaluronic acid degradation induced by hydroxy radicals and (2) standard lipid peroxidation assay in rat liver mitochondria and gastric mucosa, induced by tert-butyl hydroperoxide, were used. The in vivo approach was based on the study of the protective effect of pretreatment with ambroxol in a rat model of gastric corpus and antral lesions, induced by indomethacin. The inhibition of the degradation of hyaluronic acid was measured as a change of its viscosity; ambroxol (1,000 microl/l) reduced the degradation by 93%. Lipid peroxidation with tert-butyl hydroperoxide as a source of radicals was followed by the formation of thiobarbituric acid reactive substances. Ambroxol (10 mmol/l) inhibited lipid peroxidation by 96% in the rat liver mitochondria, and by 74% in the gastric mucosa. In vivo, ambroxol was administered p.o. at a dose of 10, 30, and 50 mg/kg, at 5, 30, and 60 min prior to indomethacin administration. The highest inhibition of the number of corpus gastric lesions and lowering of the lesion index (38% and 62%, respectively) was shown after the administration of 50 mg/kg, 30 min before indomethacin administration. Antral lesions were inhibited to a lesser extent by the same dose of ambroxol, administered 30 min before indomethacin treatment. Inhibition of the number of antral lesions reached 27% and the total area of the gastric damage was even larger (the ulcer index reached -5%).
氨溴索除具有黏液溶解作用外，还具有抗氧化和抗炎特性。对氨溴索的抗氧化作用进行了体外和体内研究。体外方法包括：（1）抑制羟基自由基诱导的透明质酸降解；（2）采用叔丁基过氧化氢诱导大鼠肝线粒体和胃黏膜的标准脂质过氧化测定法。体内研究方法是基于对在吲哚美辛诱导的大鼠胃体和胃窦损伤模型中，氨溴索预处理的保护作用的研究。通过测量透明质酸黏度变化来测定其降解抑制情况；氨溴索（1000微升/升）使降解减少了93%。以叔丁基过氧化氢作为自由基来源的脂质过氧化反应会生成硫代巴比妥酸反应性物质。氨溴索（10毫摩尔/升）在大鼠肝线粒体中抑制脂质过氧化96%，在胃黏膜中抑制74%。在体内，在给予吲哚美辛前5、30和60分钟，分别以10、30和50毫克/千克的剂量口服给予氨溴索。在给予吲哚美辛前30分钟给予50毫克/千克剂量后，胃体部损伤数量的抑制率最高，损伤指数降低（分别为38%和62%）。在吲哚美辛治疗前30分钟给予相同剂量的氨溴索，对胃窦部损伤的抑制作用较小。胃窦部损伤数量的抑制率达到27%，胃损伤总面积甚至更大（溃疡指数达到-5%）。
