Protective effect of cannabinoids on gastric mucosal lesions induced by water immersion restrain stress in rats

Objective(s): This study aimed to determine the impact of cannabinoid agonists and antagonists on the mucosal lesion progress in the stomach induced by water-immersion restraint stress (WIRS).   Materials and Methods: Rats subjected to WIRS for ۴ hr were treated with Dimethyl sulfoxide (DMSO), CBR۱ agonist (NADA ۱ mg/kg), CBR۱ antagonist (Rimonabant ۱ mg/kg), CBR۲ agonist (GW۴۰۵۸۳۳ ۱ mg/kg) or CBR۲ antagonist (AM۶۳۰ ۱ mg/kg SC) ۳۰ min before WIRS. Microscopic lesions, oxidative stress, inflammatory cytokines biomarkers, and (Myeloperoxidase) MPO in gastric tissues were determined. Results: Results indicated development of severe gastric lesions with a substantial increase in the contents of (nitric oxide) NO, (malondialdehyde) MDA,  (interleukin-۱ beta) IL-۱β, MPO, (tumor necrosis factor-alpha) TNF-α, and a significant fall in the content of GSH and the activity of  PON-۱ after WIRS. Conclusion: Treatment with NADA and AM۶۳۰ protected gastric tissues against ulcers as demonstrated by a decrease in the contents of MDA, TNF-α, MPO, and IL-۱β along with an increase in the content of PON-۱ activity and GSH in the stomach tissues. On the other hand, treatment with SR۱۴۱۷۱۶A or GW۴۰۵۸۳۳ showed no protective effects on ulcers development. It seems that cannabinoids exert their antioxidant potential and anti-inflammatory effects against  WIRS-induced gastric ulcers by activation of CB۱R.

کلیدواژه ها:

Anti-oxidant ، Cannabinoid receptor ، stress ، TNF-α ، Ulcer