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Effect of Cannabis sativa extract on gastric acid secretion, oxidative stress and gastric mucosal integrity in rats

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Abstract

Studies were conducted in pylorus-ligated rats to investigate the effect of Cannabis sativa extract on gastric acid secretion, experimental gastric ulcer and on oxidative stress and inflammatory markers in the gastric mucosa. C. sativa (5, 10 and 20 mg/kg, expressed as Δ9-tetrahydrocannabinol) was administered subcutaneously daily for 4 weeks prior to pylorus ligation and different treatments. Under basal conditions, pretreatment with cannabis extract at doses of 5 and 10 mg/kg increased gastric acid secretion and induced minimally visible gastric mucosal lesions in the 4 h pylorus-ligated rat. Malondialdehyde and nitric acid concentration increased, while reduced glutathione decreased by cannabis at doses of 5 and 10 mg/kg in gastric mucosa. TNF-α increased by cannabis extract at doses of 5 and 10 mg/kg but decreased following the high dose of 20 mg/kg. On the other hand, the gastric acid secretory responses stimulated by pentagastrin or carbachol (but not histamine) were inhibited in rats pretreated with cannabis extract. Under these conditions, cannabis decreased pepsin content after pentagastrin and carbachol but not histamine stimulation. Cannabis also decreased lipid peroxidation and nitric oxide content, and increased both reduced glutathione and catalase activity in mucosa. Moreover, cannabis decreased mucosal inflammation (level of TNF-α) and the development of gastric mucosal lesions. Cannabis administered for 1 month prior to pylorus-ligation and either acidified aspirin or ethanol (96 %) decreased the development of gastric mucosal damage in a dose-dependent manner, along with reduction in gastric acid output, gastric mucosal oxidative stress and inflammation (TNF-α). Sections of gastric mucosa stained with periodic acid Schiff showed increased mucus secretion by cannabis in basal conditions and after treatment with aspirin or ethanol. Results indicate that: (1) the effect of cannabis differs in basal conditions and after exposure of the gastric mucosa to high acid concentrations or other chemical noxious agents; (2) cannabis administered systemically exerts gastric mucosal protective effects against mucosal damage evoked by stimulation of gastric acid secretion, acidified aspirin or ethanol. These effects of cannabis are likely to involve inhibition of gastric acid and pepsin secretion, increased mucus, decreased oxidative stress and inflammation in gastric mucosa.

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Abdel-Salam, O.M.E., Salama, R.A.A., El-Denshary, EE. et al. Effect of Cannabis sativa extract on gastric acid secretion, oxidative stress and gastric mucosal integrity in rats. Comp Clin Pathol 24, 1417–1434 (2015). https://doi.org/10.1007/s00580-015-2090-3

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