Nielsen O H, Bouchelouche P N, Berild D, Ahnfelt-Rønne I
Dept. of Medical Gastroenterology C, Herlev Hospital, University of Copenhagen, Denmark.
Scand J Gastroenterol. 1993 Jun;28(6):527-32. doi: 10.3109/00365529309098261.
Activated polymorphonuclear leukocytes (PMNs), which are found in the inflammatory lesions of chronic inflammatory bowel disease, produce tissue-destructive oxygen-derived free radicals. The influence of 5-aminosalicylic acid (5-ASA), its acetylated metabolite (Ac-5-ASA), sulfasalazine (SAZ), and olsalazine (OLZ) (5-ASA dimer linked by an azo group) in pharmacologically relevant concentrations (0.1-10 mM) were tested on PMN superoxide production with either the receptor-specific agent formyl-methionyl-leucyl-phenylalanine (fMLP) or the protein kinase C activator phorbol myristate acetate (PMA). Inhibition of receptor-specific superoxide production occurred at 0.07, 0.32, and 0.63 mM (IC50 values) for 5-ASA, SAZ, and OLZ, respectively. No inhibitory effects of SAZ and OLZ were observed when PMA was applied as stimulus for PMN superoxide production. The results indicate that the signal to which PMNs respond by generating superoxide is primarily due to calcium release from intracellular stores. They further suggest that SAZ and OLZ may affect the oxygen-derived free radical production in human PMNs by unspecific cytotoxicity or by interference with the nicotinamide adenine dinucleotide phosphate, reduced (NADPH) oxidase system, whereas 5-ASA itself is a free radical scavenger.
活化的多形核白细胞（PMNs）存在于慢性炎症性肠病的炎症病变中，可产生具有组织破坏性的氧衍生自由基。使用受体特异性试剂甲酰甲硫氨酰亮氨酰苯丙氨酸（fMLP）或蛋白激酶C激活剂佛波酯（PMA），测试了药理相关浓度（0.1 - 10 mM）的5-氨基水杨酸（5-ASA）、其乙酰化代谢产物（Ac-5-ASA）、柳氮磺胺吡啶（SAZ）和奥沙拉嗪（OLZ）（通过偶氮基团连接的5-ASA二聚体）对PMN超氧化物产生的影响。5-ASA、SAZ和OLZ对受体特异性超氧化物产生的抑制作用分别在0.07、0.32和0.63 mM（IC50值）时出现。当使用PMA作为PMN超氧化物产生的刺激物时，未观察到SAZ和OLZ的抑制作用。结果表明，PMN通过产生超氧化物做出反应的信号主要是由于细胞内储存的钙释放。它们进一步表明，SAZ和OLZ可能通过非特异性细胞毒性或干扰烟酰胺腺嘌呤二核苷酸磷酸（还原型）（NADPH）氧化酶系统来影响人PMN中氧衍生自由基的产生，而5-ASA本身是一种自由基清除剂。
