Marazova K, Klouchek E, Popov A, Ivanov C, Krushkov I, Ichikawa T, Ishihara K, Hotta K
Department of Pharmacology and Toxicology, Medical Faculty, Sofia, Bulgaria.
Methods Find Exp Clin Pharmacol. 1998 Oct;20(8):667-72. doi: 10.1358/mf.1998.20.8.487495.
We have studied the effect of the newly synthesized agent, roxatidine bismuth citrate (N-[3-(3-(1-piperidinyl-methyl)phenoxy)propyl]-hydroxyacetamide-2- hydroxypropane-1,2,3-tricarboxylate-bismuth(3+) complex), code name MX1, against acetylsalicylic acid (ASA)- and indomethacin-induced gastric mucosal damage in rats. Effects of MX1 (12.5, 50, 125, 184, 250 mg/kg) were compared to the effects of equimolar doses of roxatidine and bismuth subcitrate. Effect of MX1 (10(-6) M) on mucin biosynthesis measured by [3H] glucosamine incorporation in rat gastric corpus has been determined. MX1-pretreatment dose-dependently decreased the mean ulcer number and length in all doses used in an extent similar to that of roxatidine and more pronounced in comparison with bismuth subcitrate. The morphometrical results have been confirmed histomorphologically. The biosynthesis of mucin was found to be significantly enhanced after MX1 addition. The results of the present study suggest that MX1 has a gastroprotective effect against ASA- and indomethacin-induced ulcers which might be due both to its H2-blocking and mucus-stimulating activity.
我们研究了新合成的药物罗沙替丁枸橼酸铋（代号MX1，化学名称为N-[3-(3-(1-哌啶基甲基)苯氧基)丙基]-羟基乙酰胺-2-羟基丙烷-1,2,3-三羧酸铋(3+)络合物）对大鼠乙酰水杨酸（ASA）和吲哚美辛诱导的胃黏膜损伤的影响。将MX1（12.5、50、125、184、250mg/kg）的作用与等摩尔剂量的罗沙替丁和枸橼酸铋的作用进行了比较。测定了MX1（10(-6)M）对通过[3H]氨基葡萄糖掺入大鼠胃体中测量的粘蛋白生物合成的影响。MX1预处理剂量依赖性地降低了所有使用剂量下的平均溃疡数量和长度，其程度与罗沙替丁相似，且与枸橼酸铋相比更明显。形态计量学结果已通过组织形态学得到证实。发现添加MX1后粘蛋白的生物合成显著增强。本研究结果表明，MX1对ASA和吲哚美辛诱导的溃疡具有胃保护作用，这可能归因于其H2阻断和刺激黏液的活性。
