The role of mitochondria-derived reactive oxygen species in the pathogenesis of non-steroidal anti-inflammatory drug-induced small intestinal injury

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) have been implemented in clinical settings for a long time for their anti-inflammatory effects. With the number of NSAID users increasing, gastroenterological physicians and researchers have worked hard to prevent and treat NSAID-induced gastric mucosal injury, an effort that has for the large part being successful. However, the struggle against NSAID-induced mucosal damage has taken on a new urgency due to the discovery of NSAID-induced small intestinal mucosal injury. Although the main mechanism by which NSAIDs induce small intestinal mucosal injury has been thought to depend on the inhibitory effect of NSAIDs on cyclooxygenase (COX) activity, recent studies have revealed the importance of mitochondria-derived reactive oxygen species (ROS) production, which occurs independently of COX-inhibition. ROS production is an especially important factor in the increase of small intestinal epithelial cell permeability, an early stage in the process of small intestinal mucosal injury. By clarifying the precise mechanism, together with its clinical features using novel endoscopy, effective strategies for preventing NSAID-induced small intestinal damage, especially targeting mitochondria-derived ROS production, may be developed.

ROS in gastrointestinal inflammation: Rescue Or Sabotage?

“…Similarly to NADPH oxidase‐produced ROS, mtROS were linked to SI inflammation. In a model of NSAID‐induced mucosal injury, increased barrier permeability and inflammation were associated with enhanced mtROS production and changes in mitochondrial morphology towards vacuolation, swelling and loss of cristae (Handa et al , ). In enteritis induced by Clostridium difficile infection, the increased fluid and electrolyte secretion, intestinal permeability and loss of electrical resistance were accompanied by increased ROS levels, although the source and mechanism of action were not determined (Qiu et al , ).…”

Oxidative stress, antioxidants and intestinal calcium absorption

“…Moreover, the nutritional stress produced by high-fat and high-carbohydrate diets also generates oxidative stress, which leads to initiation of pathogenic milieu and development of different chronic diseases[6-8]. ROS are also generated by other exogenous sources such as ultraviolet radiation, alcohol consumption, cigarette smoking, ingestion of nonsteroidal anti-inflammatory drugs and infections[9,10]. Ischemia/reperfusion (I/R) injuries also contribute to exacerbating ROS production[11].…”

Genome‐Wide Transcriptional Analysis Reveals the Protection against Hypoxia‐Induced Oxidative Injury in the Intestine of Tibetans via the Inhibition of GRB2/EGFR/PTPN11 Pathways

“…Many factors, such as intestinal food, are more likely to destroy the mucosal structure when intestinal mucosa is in a fragile condition [57]. Meanwhile, ROS increase the permeability of small intestinal epithelial cells and lead to intestinal mucosal injury at an early stage [58]. …”