Gastrointestinal Toxicity of Nonsteroidal Antiinflammatory Drugs

Section of Gastroenterology, Boston University, Boston, Massachusetts, United States
New England Journal of Medicine (Impact Factor: 55.87). 07/1999; 340(24):1888-99. DOI: 10.1056/NEJM199906173402407
Source: PubMed
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Available from: Marcus B. Wolfe Sr.
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    • "Among patients using NSAIDs, it is estimated that about 16,500 deaths occur every year in the United States. This figure is considerably greater than the number of deaths from multiple myeloma, asthma, cervical cancer, or Hodgkin's disease [7]. Unfortunately, many physicians and most patients are unaware of the magnitude of the problem. "
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    ABSTRACT: Aspirin is chemopreventive; however, side effects preclude its long-term use. NOSH-aspirin (NBS-1120), a novel hybrid that releases nitric oxide and hydrogen sulfide, was designed to be a safer alternative. Here we compare the gastrointestinal safety, anti-inflammatory, analgesic, anti-pyretic, anti-platelet, and chemopreventive properties of aspirin and NBS-1120 administered orally to rats at equimolar doses. Gastrointestinal safety: 6h post-administration, the number and size of hemorrhagic lesions in stomachs were counted; tissue samples were frozen for PGE2, SOD, and MDA determination. Anti-inflammatory: 1h after drug administration, the volume of carrageenan-induced rat paw edemas was measured for 5h. Anti-pyretic: fever was induced by LPS (ip) an hour before administration of the test drugs, core body temperature was measured hourly for 5h. Analgesic: time-dependent analgesic effects were evaluated by carrageenan-induced hyperalgesia. Antiplatelet: anti-aggregatory effects were studied on collagen-induced platelet aggregation of human platelet-rich plasma. Chemoprevention: Nude mice were gavaged daily for 25 days with vehicle, aspirin or NBS-1120. After one week, each mouse was inoculated subcutaneously in the right flank with HT-29 human colon cancer cells. Both agents reduced PGE2 levels in stomach tissue; however, NBS-1120 did not cause any stomach ulcers, whereas aspirin caused significant bleeding. Lipid peroxidation induced by aspirin was higher than that exerted by NBS-1120. SOD activity was significantly inhibited by aspirin but increased by NBS-1120. Both agents showed similar anti-inflammatory, analgesic, anti-pyretic, and anti-platelet activities. Aspirin increased plasma TNFα more than NBS-1120-treated animals. NBS-1120 was better than aspirin as a chemopreventive agent; it dose-dependently inhibited tumor growth and tumor mass.
    Full-text · Article · Sep 2015 · Biochemical pharmacology
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    • "Moynihan (2002) counts 450 deaths by paracetamol per year in the U.S. As the primary remedy to this hazard, Brune suggests replacing paracetamol by diclofenac, ibuprofen and other NSAIDs. But should it not be mentioned that 16,500 deaths per year were attributed to the use of NSAID in the U.S. (Wolfe et al. 1999 "

    Full-text · Article · Aug 2015 · European journal of pain (London, England)
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    • "Mild symptoms such as nausea, diarrhea, abdominal pain, loss of appetite can be demonstrated. More serious symptoms include severe damage to the upper gastrointestinal tract manifested by bleeding, ulceration, erosions and perforations (often leading to death) [5]. The lower part of the gastrointestinal tract may also be subject to such damage. "
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    ABSTRACT: Background The previous study indicated the enhancement of the anti-inflammatory effect of ketoprofen by acute and sub chronic administration of zinc hydroaspartate. Methods The present study examined anti-inflammatory, anti-ulcerogenic and analgesic activity induced by chronic (14 days) administration of ZHA (30 mg/kg, po), with a combination of a single administration of ketoprofen, in rats. Moreover, the zinc concentration in serum and stomach mucosa was also determined. Results Chronic ZHA po administration exhibits anti-inflammatory activity and enhanced the effect induced by ketoprofen. Likewise, ZHA administration demonstrated anti-ulcerogenic activity. While ZHA alone did not exhibit analgesic action, it enhanced the effect of ketoprofen. Conclusions The present study demonstrated for the first time that chronic treatment with zinc salt exhibits anti-inflammatory activity. Besides, anti-ulcerogenic activity and the enhancing properties of zinc to ketoprofen induced anti-inflammatory and analgesic activity were also shown.
    Full-text · Article · Oct 2014 · Pharmacological reports: PR
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