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Artesunate affords protection against aspirin-induced gastric injury by targeting oxidative stress and proinflammatory signaling

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Abstract

Background

Prolonged use of aspirin, a commonly prescribed non steroidal anti-inflammatory drug, is well known to produce gastrointestinal toxicity which could be minimized by various anti-secretory agents. The present study was carried out to evaluate the protective effect of artesunate against aspirin induced gastric injury in rats.

Methods

Gastric injury was induced in fasted Wistar rats by oral administration of aspirin. The effect of 50 and 150 mg/kg of artesunate was studied on macroscopic changes, gastric secretions, histology, oxidative stress and inflammatory markers in the stomach tissue after 5 h of induction of gastric injury. Immunohistochemical analysis for the expression of IL-1β, IL-6, NF-κB(p65) and COX-2 was also carried out. The effect of artesunate was compared with that of standard anti-ulcer drug famotidine (20 mg/kg).

Results

Artesunate pretreatment produced a dose-dependent reduction in aspirin induced gastric injury and restored the gastric juice parameters. It normalized the tissue levels of oxidative stress markers (glutathione, malondialdehyde and superoxide dismutase activity) and mediators of inflammation (myeloperoxidase and TNF-α). The protection afforded by artesunate was evident from the histoarchitecture of stomach tissue and marked reduction in tissue expression of IL-1β, IL-6, NF-κB(p65) and COX-2. The effect of artesunate was found to be comparable to that of standard drug famotidine.

Conclusion

Artesunate markedly ameliorated aspirin induced gastric injury in rats by targeting oxidative stress and COX-2 dependent as well as COX-2 independent proinflammatory signaling pathways and could have a therapeutic potential in gastric ulcer disease.

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Authors and Affiliations

  1. Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India

    Sneh Verma & Vijay L. Kumar

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  1. Sneh Verma
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  2. Vijay L. Kumar
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Correspondence to Vijay L. Kumar.

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Verma, S., Kumar, V.L. Artesunate affords protection against aspirin-induced gastric injury by targeting oxidative stress and proinflammatory signaling. Pharmacol. Rep 70, 390–397 (2018). https://doi.org/10.1016/j.pharep.2017.06.003

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