title: Attenuation of gastric mucosal damage by artesunate in rat: Modulation of oxidative stress and NFκB mediated signaling.
abstract: A number of factors like alcohol consumption, stress, use of non steroidal anti-inflammatory drugs and acidity are well known to increase the risk of development of gastric ulcers. The present study was carried out to investigate the protective effect of artesunate against gastric injury induced in rats by oral administration of ethanol and by pylorus ligation in independent sets of experiments. The groups included in each set (n = 6 per group) were normal control, experimental control and drug treated groups: artesunate 50 and 150 mg/kg (ART 50 and ART 150) and famotidine 20 mg/kg (FAM 20). Artesunate and famotidine were given orally 1 h before induction of gastric ulceration and the macroscopic changes, median ulcer score, gastric juice parameters (volume, pH and acidity), markers of oxidative stress and inflammation (GSH, SOD, TBARS and MPO) and tissue histology were evaluated in both the models. The study was extended further for determination of tissue levels of TNF-α and expression of IL-1β, IL-6 and NFκB (p65) in ethanol induced gastric ulcer model. The results of the present study show that pretreatment with artesunate significantly decreased hemorrhagic lesions and mucosal damage with marked reduction in median ulcer score in both the models. The protective effect of artesunate was concomitant with dose-dependent normalization of gastric juice parameters, markers of oxidative stress and lipid peroxidation. The ameliorative effect of artesunate was also supported by restoration of histological architecture. Furthermore, artesunate pretreatment also alleviated the gastric mucosal inflammation as revealed by significant decrease in the tissue level of pro-inflammatory cytokine TNF-α (p < 0.01) and tissue expression of IL-1β, IL-6 and NFκB (p65). The protective effect of artesunate was found to be comparable to that of famotidine. Conclusively, artesunate afforded significant gastroprotection in rat due to its anti-oxidant and anti-inflammatory properties with transcription factor NFκB(p65) and its downstream inflammatory cascade as a plausible target for its action.
authors.affiliation: Department of Pharmacology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India.
authors.forename: Sneh
authors.initials: S
authors.lastname: Verma
authors.affiliation: Department of Pharmacology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India. Electronic address: kumarvl98@hotmail.com.
authors.forename: Vijay L
authors.initials: VL
authors.lastname: Kumar
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants; D037621:Artemisinins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000077332:Artesunate; D016207:Cytokines / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000293:injuries; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D013276:Stomach Ulcer / Q000188:drug therapy / Q000517:prevention & control*; D051996:Transcription Factor RelA / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D000897:Anti-Ulcer Agents; D000975:Antioxidants; D037621:Artemisinins; D016207:Cytokines; D051996:Transcription Factor RelA; D000077332:Artesunate
keywords: Artesunate; Ethanol; Gastroprotective; Inflammation; Oxidative stress; Pyloric ligation