Digestive diseases and sciences
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Comparative Study
Effects of dipyrone on inflammatory infiltration and oxidative metabolism in gastric mucosa: comparison with acetaminophen and diclofenac.
In the last several years, it has been proposed that neutrophil- and oxygen-dependent microvascular injuries may be important factors in the gastrointestinal toxicity of nonsteroidal antiinflammatory drugs (NSAIDs). In addition, after oral administration, reduced levels of gastric mucosal adenosine triphosphate in response to mitochondrial damage constitute the earliest event on topical mucosal erosions. In these experiments, we compared the implication of active oxygen, lipid peroxidation levels and neutrophil infiltration in gastric mucosal injury induced by the analgesic-antipyretic drugs, dipyrone (pyrazolone derivative) and acetaminophen (nonacidic drug), both with relatively weak antiinflammatory effects, with diclofenac (an acidic NSAID). ⋯ None of treatments induced changes in xanthine oxidase activity, an index of ischemic condition. These findings confirm the favorable gastric tolerability of dipyrone, since only the highest dose produced weak mucosal lesions similar to that obtained with acetaminophen, and this effect only could be related to a diminished glutathione metabolism. In contrast, diclofenac induced significant erosions, and the data obtained indicate that the enhancement of oxidative stress plays an important role in the pathogenesis of damage.