Danielak Aleksandra, Wallace John L, Brzozowski Tomasz, Magierowski Marcin
Department of Physiology, Jagiellonian University Medical College, Cracow, Poland.
Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada.
Front Pharmacol. 2021 Apr 29;12:657457. doi: 10.3389/fphar.2021.657457. eCollection 2021.
Non-steroidal anti-inflammatory drugs (NSAIDs) represent one of the most widely used classes of drugs and play a pivotal role in the therapy of numerous inflammatory diseases. However, the adverse effects of these drugs, especially when applied chronically, frequently affect gastrointestinal (GI) tract, resulting in ulceration and bleeding, which constitutes a significant limitation in clinical practice. On the other hand, it has been recently discovered that gaseous mediators nitric oxide (NO), hydrogen sulfide (HS) and carbon monoxide (CO) contribute to many physiological processes in the GI tract, including the maintenance of GI mucosal barrier integrity. Therefore, based on the possible therapeutic properties of NO, HS and CO, a novel NSAIDs with ability to release one or more of those gaseous messengers have been synthesized. Until now, both preclinical and clinical studies have shown promising effects with respect to the anti-inflammatory potency as well as GI-safety of these novel NSAIDs. This review provides an overview of the gaseous mediators-based NSAIDs along with their mechanisms of action, with special emphasis on possible implications for GI mucosal defense mechanisms.
非甾体抗炎药（NSAIDs）是使用最为广泛的一类药物之一，在众多炎症性疾病的治疗中发挥着关键作用。然而，这些药物的不良反应，尤其是长期应用时，常常会影响胃肠道（GI），导致溃疡和出血，这在临床实践中构成了重大限制。另一方面，最近发现气态介质一氧化氮（NO）、硫化氢（HS）和一氧化碳（CO）参与胃肠道的许多生理过程，包括维持胃肠道黏膜屏障的完整性。因此，基于NO、HS和CO可能的治疗特性，已合成出一种能够释放一种或多种这些气态信使的新型NSAIDs。到目前为止，临床前和临床研究均已表明，这些新型NSAIDs在抗炎效力以及胃肠道安全性方面具有令人期待的效果。本综述概述了基于气态介质的NSAIDs及其作用机制，特别强调了其对胃肠道黏膜防御机制的潜在影响。
