Article

Gastrointestinal Toxicity of Nonsteroidal Antiinflammatory Drugs

Section of Gastroenterology, Boston University School of Medicine and Boston Medical Center, MA 02118-2393, USA.
New England Journal of Medicine (Impact Factor: 54.42). 07/1999; 340(24):1888-99. DOI: 10.1056/NEJM199906173402407
Source: PubMed
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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.
    Pharmacological reports: PR 10/2014; 66(5). DOI:10.1016/j.pharep.2014.05.007 · 2.17 Impact Factor
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    • "Traditional non-steroidal anti-inflammatory drugs (NSAIDs) which inhibit both COX subtypes are still the most commonly used medications for inflammation and pain (Salgin-Goksen et al., 2007). However, it is well known that NSAIDs have several serious side effects such as gastric ulceration, renal injury and cardiotoxicity (Allison et al., 1992; Wolfe et al., 1999). To limit the risk of GI damage induced by NSAIDs, highly selective COX-2 inhibitors (coxibs) have been developed where they exhibited equivalent anti-inflammatory/analgesic activities to those of non-selective COX inhibitors but with least GI toxicity (Micklewright et al., 2003). "
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    ABSTRACT: A novel set of 4-substituted-1-phenyl-pyrazolo[3,4-d]pyrimidine and 5-substituted-1-phenyl-pyrazolo[3,4-d]pyrimidin-4-one derivatives were synthesized and evaluated as potential anti-inflammatory agents. The newly prepared compounds were assessed through the examination of their in vitro inhibition of four targets; cyclooxygenases subtypes (COX-1 and COX-2), inducible nitric oxide synthase (iNOS) and nuclear factor kappa B (NF-κB). Compounds 8a, 10c and 13c were the most potent and selective ligands against COX-2 with inhibition percentages of 79.6, 78.7 and 78.9% at a concentration of 2 μM respectively, while compound 13c significantly inhibited both COX subtypes. On the other hand, fourteen compounds showed high iNOS inhibitory activities with IC50 values in the range of 0.22-8.5 μM where the urea derivative 11 was the most active compound with IC50 value of 0.22 μM. Most of the tested compounds were found to be devoid of inhibitory activity against NF-kB. Moreover, almost all compounds were not cytotoxic, (up to 25μg/ml), against a panel of normal and cancer cell lines. The in silico docking results were in agreement with the in vitro inhibitory activities against COXs and iNOS enzymes. The results of in vivo anti-inflammatory and antinociceptive studies were consistent with that of in vitro studies which confirmed that compounds 8a, 10c and 13c have significant anti-inflammatory and analgesic activities comparable to that of the control, ketorolac. Taken together, dual inhibition of COXs and iNOS with novel pyrazolopyrimidine derivatives is a valid strategy for the development of anti-inflammatory/analgesic agents with the probability of fewer side effects.
    European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 06/2014; 62. DOI:10.1016/j.ejps.2014.05.025 · 3.01 Impact Factor
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    • "Consequently, plant extracts are being extensively evaluated to identify novel anti-inflammatory compounds and ethnopharmacological studies have contributed to important insights into the identity of novel anti-inflammatory and gastro-protective compounds of medicinal value [3] [4]. Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most widely used drug classes in the world even though their continued usage can cause gastritis [5]. It is generally believed that NSAID-induced gastric damage is caused by suppression of gastric prostaglandin synthesis [6]. "
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    ABSTRACT: Infusions of Picrolemma sprucei roots, stems and leaves are used in traditional medicine throughout the Amazon region from the Guianas to Brazil and Peru in the treatment of gastritis, intestinal helminths and malaria. As there are no studies describing its mode of action in providing a gastroprotective effect, we determined herein that one of the main constituents found in P. sprucei infusions, the quassinoid isobrucein B (IsoB), reduces some of the pathophysiological effects in a mouse model of non-steroidal anti-inflammatory drug (NSAID)-induced gastritis and provide mechanisms of action. Then, IsoB (1.17 g) was isolated from the roots and stems (6.5 kg) of P. sprucei. Its structure was confirmed by 1D and 2D (1)H and (13)C NMR, ESI-tof-MS, IR and UV. C57BL/6 strain mice were subcutaneously injected with IsoB (0.5-5 mg∙kg(-1)) or vehicle before oral administration of indomethacin and sacrificed later at different times points. Gastric damage was assessed by measuring lesion length. Leukocyte migration was evaluated based on leukocyte rolling and adhesion using intravital microscopy in the mesenteric microcirculation and tissue MPO activity. Stomach extract cytokine (TNFα, IL-1β and KC/CXCL1) and prostaglandin E2 (PGE2) levels were measured by ELISA and RIA, respectively. IsoB pre-treatment (0.5-5.0 mg∙kg(-1)) significantly reduced the formation of indomethacin-induced stomach lesions in a dose-dependent manner. The decrease in stomach lesions was associated with less observed leukocyte rolling, decreased leukocyte adhesion and less neutrophil infiltration (MPO activity). IsoB (1 mg∙kg(-1)) pre-treatment did not prevent indomethacin-induced decreases in stomach PGE2 levels. However, IL-1β and KC/CXCL1 levels were inhibited by this same IsoB dosage, whereas TNF-α was unchanged. IsoB may be a prototypic compound to provide protective effects against NSAID -induced gastritis and possibly other gastropathies. Moreover, IsoB gastroprotective action may be due to a reduction in IL-1β and KC/CXCL1 production/release and leukocyte rolling, adhesion and migration.
    Fitoterapia 03/2014; 95. DOI:10.1016/j.fitote.2014.02.008 · 2.22 Impact Factor
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