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首页> 外文期刊>Biochemical Pharmacology >NOSH-aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid has enhanced chemo-preventive properties compared to aspirin, is gastrointestinal safe with all the classic therapeutic indications
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NOSH-aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid has enhanced chemo-preventive properties compared to aspirin, is gastrointestinal safe with all the classic therapeutic indications

机译：NOSH-阿司匹林（NBS-1120）是一种新型的释放一氧化氮和硫化氢的杂化物，与阿司匹林相比具有增强的化学预防性能，在胃肠道中具有所有经典的治疗适应症

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Aspirin is chemopreventive; however, side effects preclude its long-term use. NOSH-aspirin (NBS-1120), a novel hybrid that releases nitric oxide and hydrogen sulfide, was designed to be a safer alternative. Here we compare the gastrointestinal safety, anti-inflammatory, analgesic, anti-pyretic, anti-platelet, and chemopreventive properties of aspirin and NBS-1120 administered orally to rats at equimolar doses. Gastrointestinal safety: 6 h post-administration, the number and size of hemorrhagic lesions in stomachs were counted; tissue samples were frozen for PGE(2), SOD, and MDA determination. Anti-inflammatory: 1 h after drug administration, the volume of carrageenan-induced rat paw edemas was measured for 5 h. Anti-pyretic: fever was induced by LPS (ip) an hour before administration of the test drugs, core body temperature was measured hourly for 5 h. Analgesic: time-dependent analgesic effects were evaluated by carrageenan-induced hyperalgesia. Antiplatelet: anti-aggregatory effects were studied on collagen-induced platelet aggregation of human platelet-rich plasma. Chemoprevention: nude mice were gavaged daily for 25 days with vehicle, aspirin or NBS-1120. After one week, each mouse was inoculated subcutaneously in the right flank with HT-29 human colon cancer cells. Both agents reduced PGE2 levels in stomach tissue; however, NBS-1120 did not cause any stomach ulcers, whereas aspirin caused significant bleeding. Lipid peroxidation induced by aspirin was higher than that exerted by NBS-1120. SOD activity was significantly inhibited by aspirin but increased by NBS-1120. Both agents showed similar anti-inflammatory, analgesic, anti-pyretic, and anti-platelet activities. Aspirin increased plasma TNF alpha more than NBS-1120-treated animals. NBS-1120 was better than aspirin as a chemopreventive agent; it dose-dependently inhibited tumor growth and tumor mass. (C) 2015 Elsevier Inc. All rights reserved.
机译：阿司匹林具有化学预防作用;但是，副作用使其无法长期使用。 NOSH-阿司匹林（NBS-1120）是一种释放一氧化氮和硫化氢的新型杂合物，被设计为一种更安全的替代品。在这里，我们比较了以等摩尔剂量口服给予大鼠阿司匹林和NBS-1120的胃肠道安全性，消炎，镇痛，解热，抗血小板和化学预防特性。胃肠道安全性：给药后6小时，计算胃中出血性病变的数量和大小;将组织样品冷冻以进行PGE（2），SOD和MDA测定。抗炎：给药1小时后，测定角叉菜胶诱导的大鼠爪水肿的体积5小时。解热：在给予测试药物前一小时，由LPS（ip）引起发烧，每小时测量核心体温5小时。镇痛药：通过角叉菜胶诱导的痛觉过敏来评估时间依赖性镇痛作用。抗血小板：研究了胶原蛋白诱导的富含血小板的血浆中血小板聚集的抗聚集作用。化学预防：每天将裸鼠与赋形剂，阿司匹林或NBS-1120一起灌胃25天。一周后，将每只小鼠的右侧腹皮下接种HT-29人结肠癌细胞。两种药物均可降低胃组织中的PGE2水平。然而，NBS-1120并未引起任何胃溃疡，而阿司匹林则引起大量出血。阿司匹林引起的脂质过氧化作用高于NBS-1120。阿司匹林显着抑制了SOD活性，但NBS-1120却增加了SOD活性。两种药物均显示出相似的抗炎，镇痛，解热和抗血小板活性。阿司匹林比NBS-1120处理的动物增加的血浆TNFα含量更高。 NBS-1120作为化学预防剂优于阿司匹林;它剂量依赖性地抑制肿瘤的生长和肿块。 （C）2015 Elsevier Inc.保留所有权利。

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