ACTIONS OF SULFASALAZINE AND 5-AMINOSALICYLIC ACID AS REACTIVE OXYGEN SCAVENGERS IN THE SUPPRESSION OF BILE ACID-INDUCED INCREASES IN COLONIC EPITHELIAL-CELL LOSS AND PROLIFERATIVE ACTIVITY
ACTIONS OF SULFASALAZINE AND 5-AMINOSALICYLIC ACID AS REACTIVE OXYGEN SCAVENGERS IN THE SUPPRESSION OF BILE ACID-INDUCED INCREASES IN COLONIC EPITHELIAL-CELL LOSS AND PROLIFERATIVE ACTIVITY
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DOI：
10.1016/0016-5085(87)90635-4
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发表时间：
1987-06-01
期刊：
影响因子：
29.4
通讯作者：
DERUBERTIS, FR
中科院分区：
文献类型：
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作者：
CRAVEN, PA;PFANSTIEL, J;DERUBERTIS, FR
柳氮磺胺吡啶抑制溃疡性结肠炎患者的粘膜损伤，但其治疗作用的机制尚不清楚。在本研究中，我们研究了柳氮磺胺吡啶在大鼠模型中的保护作用的机制，在该模型中，结肠上皮细胞的损失和随后的上皮细胞增殖活性的增加是由脱氧胆酸钠的结肠内滴注诱导的。柳氮磺胺吡啶或其治疗活性代谢物5-氨基水杨酸抑制了脱氧核糖核酸进入结肠腔的损失，以及随后由脱氧胆酸钠诱导的粘膜鸟氨酸脱羧酶活性和氚化胸苷掺入脱氧核糖核酸的增加。柳氮磺胺吡啶和5-氨基水杨酸也阻断了黄嘌呤-黄嘌呤氧化酶诱导的脱氧核糖核酸丢失和随后的增殖反应。体外脱氧胆酸钠增加活性氧形成的结肠粘膜刮片或孤立的隐窝上皮。脱氧胆酸钠对活性氧形成的这些作用可被柳氮磺胺吡啶或5-氨基水杨酸阻断。柳氮磺胺吡啶是柳氮磺胺吡啶的一种无治疗活性的代谢产物，对脱氧胆酸钠诱导的表面细胞脱落、鸟氨酸脱羧酶、氚化胸苷掺入脱氧核糖核酸、化学发光或超氧化物产生的增加没有影响。柳氮磺胺吡啶和5-氨基水杨酸抑制活性氧的能力可能在其治疗炎症性肠病的作用中发挥作用。
Sulfasalazine suppresses mucosal injury in patients with ulcerative colitis, but the mechanism of its therapeutic action is uncertain. In the present study, we examined the mechanism of the protective action of sulfasalazine in a rat model in which colonic epithelial cell loss and subsequent increases in epithelial proliferative activity was induced by intracolonic instillation of sodium deoxycholate. Sulfasalazine or its therapeutically active metabolite 5-aminosalicylic acid suppressed the loss of deoxyribonucleic acid into the colonic lumen and the subsequent increases in mucosal ornithine decarboxylase activity and tritiated thymidine incorporation into deoxyribonucleic acid induced by sodium deoxycholate. Sulfasalazine and 5-aminosalicylic acid also blocked xanthine-xanthine oxidase-induced loss of deoxyribonucleic acid and the subsequent proliferative response. In vitro sodium deoxycholate increased reactive oxygen formation by colonic mucosal scrapings or isolated crypt epithelium. These actions of sodium deoxycholate on reactive oxygen formation were blocked by sulfasalazine or 5-aminosalicylic acid. Sulfapyridine, a therapeutically inactive metabolite of sulfasalazine, had no effect on sodium deoxycholate-induced increases in surface cell sloughing, ornithine decarboxylase, tritiated thymidine incorporation into deoxyribonucleic acid, chemiluminescence, or superoxide production. The ability of sulfasalazine and 5-aminosalicylic acid to scavenge reactive oxygen may play a role in their therapeutic effects of inflammatory bowel disease.