The injurious effects of NSAIDs on the small intestine were not fully appreciated until the widespread use of capsule endoscopy. It is estimated that over two-thirds of regular NSAID users develop injury in the small intestinal injuries and that these injuries are more common than gastroduodenal mucosal injuries. Recently, chronic low-dose aspirin consumption was found to be associated with injury to the lower gut and to be a significant contributing factor in small bowel ulceration, hemorrhage, and strictures. The ability of aspirin and NSAIDs to inhibit the activities of cyclooxygenase (COX) contributes to the cytotoxicity of these drugs in the gastrointestinal tract. However, many studies found that, in the small intestine, COX-independent mechanisms are the main contributors to NSAID cytotoxicity. Bile and Gram-negative bacteria are important factors in the pathogenesis of NSAID enteropathy. Here, we focus on a promising strategy to prevent NSAID-induced small intestine injury. Selective COX-2 inhibitors, prostaglandin derivatives, mucoprotective drugs, phosphatidylcholine-NSAIDs, and probiotics have potential protective effects on NSAID enteropathy. 1. Introduction Nonsteroidal anti-inflammatory drug- (NSAID-) induced lower gastrointestinal (GI) injury is more common than NSAID-associated gastropathy [1–8]. Historically, this has been given little clinical attention since NSAID-induced enteropathy is usually asymptomatic and is not easily detected using most common diagnostic testing modalities [9, 10]. Recently, through the introduction of capsule endoscopy and device-assisted endoscopy, NSAID enteropathy has become a popular topic of study [11] particularly since NSAID enteropathy is one of the most common causes of obscure GI bleeding [11, 12]. Until recently, no new promising drugs have been developed for NSAID-induced enteropathy. Many efforts to determine the mechanism of NSAID-induced intestinal injury and preventive modalities have been made through experiments and clinical capsule studies (Tables 1 and 2). In this paper, we intend to review potential candidates for the prevention of NSAID-induced small intestinal injuries. Table 1: Proposed pathophysiologic mechanism and protection of NSAID-induced small intestinal injuries. Table 2: Clinical trials using capsule endoscopy about protective effect on NSAID-induced small intestinal injuries. 2. Proton Pump Inhibitors It is not completely clear how NSAIDs damage the lower GI tract. In contrast to the stomach, there is no evidence that gastric acid plays a role in the pathogenesis of
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