Pharmacological evidence for the participation of NO-_cGMP-K _ATP pathway in the gastric protective effect of curcumin against indomethacin-induced gastric injury in the rat

Curcumin, main compound obtained from rizhoma of Curcuma longa, shows antitumoral, antioxidant, anticarcinogenic and gastric protective properties. Recently, it has been demonstrated that curcumin exerts its gastric protective action due to an increase in gastric nitric oxide (NO) levels. However, it is unknown whether these increased NO levels are associated with activation of intracellular signaling pathways. Thus, the purpose of this study was to investigate the role of NO-_cGMP-K_ATP pathway in the gastric protective effect of curcumin during indomethacin-induced gastric injury in the rat. Adult female Wistar rats were gavaged with curcumin (3-300 mg/kg, p.o.) or omeprazole (30 mg/kg, p.o.) 30 min before indomethacin insult (30 mg/kg, p.o.). Other groups of rats were administered L-NAME (70 mg/kg, i.p.; inhibitor of nitric oxide synthase), ODQ (10 mg/kg, i.p.; inhibitor of soluble guanylate cyclase) or glibenclamide (1 mg/kg, i.p.; blocker of ATP-sensitive potassium (K_ATP) channels) 30 min before curcumin (30 mg/kg, p.o.). 3 h after indomethacin administration, rats were sacrificed and gastric injury was evaluated by determining total damaged area. A sample of gastric tissue was harvested and processed to quantify organic nitrite levels. Curcumin significantly protected against indomethacin-induced gastric injury and this effect was comparable to gastroprotective effect by omeprazole. L-NAME, ODQ and glibenclamide significantly prevented the curcumin-mediated gastric protective effect in the indomethacin-induced gastric injury model. Furthermore, curcumin administration induced a significant increase in gastric nitric oxide levels as compared to vehicle administration. Our results show for the first time that curcumin activates NO/_cGMP/K_ATP pathway during its gastro protective action.