Total Antioxidant Effects of Esomeprazole in Dyspeptic Patients Receiving Non-steroidal Anti-inflammatory Drugs
Total Antioxidant Effects of Esomeprazole in Dyspeptic Patients Receiving Non-steroidal Anti-inflammatory Drugs
The principal investigator hypothesizes that participants receiving NSAID drugs with
 dyspeptic symptoms have increased production of gastric levels of free radicals. The primary
 objective of the study is to determine if Esomeprazole Magnesium increases gastric total
 antioxidant capacity and decreases gastric free radical production in humans. Participants
 (age 18 years and older) with no history of upper GI bleeding who are receiving non-steroidal
 anti-inflammatory drugs and then develop dyspepsia will be recruited from our primary care
 clinic in Washington, DC. All eligible participants will undergo biopsies of antrum and
 corpus. The participants will be randomized to receive either Zantac OTC or Nexium for 15
 days. On day 15, all participants will undergo repeat upper endoscopy to obtain biopsies of
 antrum and corpus. Tissue samples will then be extracted to determine total antioxidant
 capacity and lipid peroxide levels (as an indirect marker of free radical production).
An extensive meta-analysis has confirmed that dyspeptic symptoms are common in individuals
 using non-steroidal anti-inflammatory drugs (NSAIDs) (1). Both esomeprazole 20 mg daily and
 esomeprazole 40 mg daily have been shown to be more effective than placebo for the control of
 upper gastrointestinal symptoms in patients receiving NSAIDs (2).

 The mechanisms by which H, K-ATPase inhibitors protect against NSAID gastropathy remain
 unclear, although it is known that their use is more clinically effective than the use of the
 H2-receptor antagonist, ranitidine (3).

 The biochemical basis for NSAID gastropathy is not fully understood (6). One potential
 mechanism for the development of gastric damage in individuals receiving NSAIDs is oxidative
 stress related to depletion of gastric antioxidants. A recent endoscopic study in patients
 supports the hypothesis that NSAID use associated with gastric bleeding decreases gastric
 mucosal glutathione levels (7), a major cellular micronutrient antioxidant produced by
 mammalian cells. The principal investigator has been working on the possibility that
 activation of afferent nerve fibers by oxidative stress can induce abdominal discomfort
 during the use of NSAIDs. This notion is supported by animal studies that have shown that
 oxidants evoke neurotransmitter release from enteric neurons (8). This experimental result
 suggests that abnormal tissue levels of oxygen-derived free radicals (oxidative stress) could
 directly activate afferent enteric nerves or could alter gastric motility via a neuronal
 mechanism.

 The hypothesis of this present proposal is that participants receiving NSAID drugs with
 dyspeptic symptoms have increased production of gastric levels of free radicals. The primary
 aims of this study are to examine gastric free radical production and total antioxidant
 capacity in participants who are taking NSAID drugs and have dyspeptic symptoms. Gastric free
 radical production and total antioxidant capacity will be measured before and after receiving
 either 15 days of daily esomeprazole magnesium or ranitidine.
Inclusion Criteria:

 -  Participants who are capable of providing informed consent, ages 18 years old and
 older. Partipants who are taking non-steroidal anti-inflammatory drugs on a daily
 basis must present with at least a 1 week history of dyspeptic symptoms including
 epigastric or upper abdominal discomfort or pain.

 Exclusion Criteria:

 -  Participants presenting with only a complaint of heartburn will be excluded.
 Participants with alarm symptoms of vomiting, evidence of bleeding, inadvertent weight
 loss, or dysphagia will be excluded. Participants will be excluded if they have had
 upper endoscopy within 6 months prior to randomization. At the initial visit,
 participants will have a Helicobacter pylori IgG serology drawn and all participants
 with a positive serology will be excluded. Participants with a previous history of
 myocardial infarction, cerebrovascular infarction, gastric or duodenal ulcer disease,
 or carcinoma will be excluded. The study will not enroll participants who have
 received a H, K-ATPase inhibitor within the past 2 weeks. At the initial upper
 endoscopy, all participants with esophageal ulcer, esophageal cancer, gastric ulcer,
 gastric cancer, and duodenal ulcer will be excluded.