Molecular Mechanisms of the Gastric Toxicity of Antirheumatic Drugs
Gastric toxicity of non-steroidal antiinflammatory drugs has been suggested to be due to inhibition of prostaglandin synthesis. Proquazone, which is less ulcerogenic than indomethacin, however, is a more potent inhibitor of gastric mucosal prostaglandin synthesis than indomethacin in vitro and equally effective in vivo. These results indicate that additional factors such as pharmacokinetic properties contribute to the gastric toxicity of non-steroidal antiinflammatory drugs. Furthermore, lipoxygenase products of arachidonic acid metabolism might modulate the effects of inhibition of prostaglandin synthesis by non-steroidal antiinflammatory drugs. Using a radioimmunoassay for leukotriene C4 the capacity of ovalbumin-sensitized guinea pig gastric mucosa to release leukotriene C4-like immunoreactivity after antigenic challenge has been demonstrated.
Key wordsNon-steroidal antiinflammatory drugs Prostaglandins Cyclooxygenase Lipoxygenase Leukotrienes Proquazone Indomethacin
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