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PO3-5-5

Artesunate affords gastroprotection by modulating oxidative stress and NFκB mediated proinflammatory signaling

[Speaker] Vijay L. Kumar:1
[Co-author] Sneh Verma:1
1:Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India

Background The risk of occurrence of gastric ulcers is well known to increase by alcohol consumption¸ stress, use of non-steroidal anti-inflammatory drugs and H. pylori infection. Its pathogenesis and loss of mucosal integrity has been related to the generation of free radicals and release of inflammatory cytokines. We have evaluated the protective effect of artesunate, an antimalarial drug¸ against gastric mucosal damage induced experimentally in rats.
Methods Gastric mucosal damage was induced by alcohol¸ pyloric ligation and aspirin. The study included respective normal control¸ experimental control and drug treated groups where two doses of artesunate (50 and 150 mg/kg) and one dose of famotidine (20 mg/kg) were administered orally 1 h before inducing ulcers. The experiments were terminated and the parameters indicating mucosal integrity¸ gastric secretary activity¸ levels of oxidative stress and inflammation markers¸ tissue histology and immunoreactivity were evaluated.
Results Gastric mucosal damage induced in three different ways exhibited distinct appearance of mucosal surface. Induction with ethanol produced hemorrhagic streaks¸ with pyloric ligation produced hyperemia¸ erosion and ulceration while with high dose aspirin edema and hemorrhage were observed. Treatment with artesunate produced a dose-dependent reduction in ulcer score in all the three models with restorative effect on tissue architecture and gastric juice parameters like pH and acidity. It also reduced oxidative stress as indicated by levels of GSH¸ TBARS¸ SOD and MPO and release of TNF-α. The enhanced expression of IL-1β¸ IL-6¸ COX-2 and NFκB(p65) observed in experimental control was also brought down with artesunate. Similar protection was also exhibited by H2 receptor blocking drug famotidine.
Conclusions Our study shows that artesunate exhibits anti-secretary and acid lowering properties and ameliorates gastric mucosal damage by inhibiting free radical¸ COX-2 and NFκB mediated pro-inflammatory signaling. These findings suggest that artesunate has a potential to be used in the treatment of gastric ulcer disease.

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