Flannigan Kyle L, Wallace John L
15 Prince Arthur Avenue, Toronto, Ontario, M5R 1B2, Canada.
Curr Pharm Des. 2015;21(21):3012-22. doi: 10.2174/1381612821666150514105413.
Hydrogen sulfide has potent anti-inflammatory and cytoprotective properties. In the gastrointestinal tract, hydrogen sulfide contributes significantly to mucosal defence and responses to injury. This includes promotion of resolution of inflammation and healing. Inhibition of hydrogen sulfide synthesis increases the susceptibility of the gastrointestinal mucosa to injury and delays healing processes. The beneficial effects of hydrogen sulfide have been exploited in the design of novel anti-inflammatory drugs that cause negligible gastrointestinal damage. Nonsteroidal anti-inflammatory drugs are known to be effective, when used chronically, in reducing the incidence of several types of cancer. However, the toxicity of these drugs, particularly in the gastrointestinal tract, greatly limits this use. On the other hand, the gastrointestinal-safe, hydrogen sulfide-releasing anti-inflammatories show great promise for chemoprevention of cancers. This paper reviews the evidence supporting important anti-inflammatory and cytoprotective effects of hydrogen sulfide, particularly in the gastrointestinal tract. Also reviewed are the approaches taken to develop safer anti-inflammatory and cancer chemopreventive drugs by exploiting the beneficial effects of hydrogen sulfide.
硫化氢具有强大的抗炎和细胞保护特性。在胃肠道中,硫化氢对黏膜防御及损伤反应起着重要作用。这包括促进炎症消退和愈合。抑制硫化氢合成会增加胃肠道黏膜对损伤的易感性,并延缓愈合过程。硫化氢的有益作用已被用于设计对胃肠道损伤可忽略不计的新型抗炎药物。已知非甾体抗炎药长期使用时可有效降低多种癌症的发病率。然而,这些药物的毒性,尤其是在胃肠道方面,极大地限制了其使用。另一方面,胃肠道安全的、释放硫化氢的抗炎药在癌症化学预防方面显示出巨大潜力。本文综述了支持硫化氢重要抗炎和细胞保护作用的证据,特别是在胃肠道中的作用。还综述了通过利用硫化氢的有益作用来开发更安全的抗炎和癌症化学预防药物的方法。