Rescue strategies against non‐steroidal anti‐inflammatory drug‐induced gastroduodenal damage

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly prescribed drugs worldwide, which attests to their efficacy as analgesic, antipyretic and anti-inflammatory agents as well as anticancer drugs. However, NSAID use also carries a risk of major gastroduodenal events, including symptomatic ulcers and their serious complications that can lead to fatal outcomes. The development of "coxibs" (selective cyclooxygenase-2 [COX-2] inhibitors) offered similar efficacy with reduced toxicity, but this promise of gastroduodenal safety has only partially been fulfilled, and is now dented with associated risks of cardiovascular or intestinal complications. Recent advances in basic science and biotechnology have given insights into molecular mechanisms of NSAID-induced gastroduodenal damage beyond COX-2 inhibition. The emergence of newer kinds of NSAIDs should alleviate gastroduodenal toxicity without compromising innate drug efficacy. In this review, novel strategies for avoiding NSAID-associated gastroduodenal damage will be described.

Prevention of Gastric Ulcers

“…Despite the protective role of this gas against mucosal injury, it suspected that hydrogen sulphide may contribute to the pro-inflammatory actions in Helicobacter pylori infection. Nevertheless, with non-steroidal anti-inflammatory drugs, hydrogen sulfide provide gastric protection by inducing up-regulation of anti-inflammatory and cyto-protective genes, including hemeoxygenase-1, vascular endothelial growth factor, insulin-like growth factor receptor and several genes associated with the transforming growth factor-receptor signaling pathway (Lim et al, 2009). A number of therapeutic possibilities combining hydrogen sulfide with non-steroidal antiinflammatory drugs are considered in early stages of development.…”

“…Furthermore, this gaseous mediator reduces non-steroidal anti-inflammatory drugs-induced leukocyte adhesion to vascular endothelial cell. The combination causes reversal of the increased expression of tumor necrosis factor-and improvement prostaglandin E 2 synthesis impaired by non-steroidal anti-inflammatory drugs (Lim et al, 2009). …”

“…Thus, activation of peroxisome proliferation-activated receptors during non-steroidal anti-inflammatory drugs administration blocks the production of inflammatory response markers, such endothelin-1, vascular cell adhesion molecule-1 in endothelial cells and tissue factors as matrix metalloproteinase-3 and tumor necrosis factor-in macrophages. These anti-inflammatory actions are mediated by inhibition of pro-inflammatory transcription pathways as nuclear factor-κB, activator protein-1 and nuclear factor of activated T cells (Lim et al, 2009). …”

“…In addition, Lipoxin A 4 can inhibit inflammatory pain processing and regulate trans-epithelial electrical resistance. Antagonism of Lipoxin A 4 receptor can significantly exacerbate gastric ulcer (Lim et al, 2009). …”

Gastric Barrier Function and Toxic Damage

“…Development of ‘coxibs' (selective cyclooxygenase-2, COX-2, inhibitors) offered similar efficacy with reduced toxicity, but coxibs are now dented with associated risks of cardiovascular or intestinal complications. Recent advances in basic science and biotechnology have given insights into molecular mechanisms of NSAID-induced GI damage and have led to the development of potential newer therapeutics, including COX and lipoxygenase dual-inhibiting NSAIDs, NO-releasing NSAIDs, H 2 S-releasing NSAIDs, zinc-conjugated NSAIDs, and NSAIDs in combination with phosphatidylcholine [36]. …”