Efficiency evaluation of Amlodipine combined with N-acetylcysteine on Indomethacin-induced gastritis in rats

Abstract

Introduction: It is a well-known phenomenon that nonsteroidal anti-inflammatory drugs cause gastric mucosal damage. Amlodipine is a third generation dihydropyridine-type calcium channel blocker; it can inhibit inflammatory cytokines and enhance antioxidant defenses. N-acetylcysteine can act both as a precursor of reduced glutathione and as a direct ROS scavenger. Moreover, N-acetylcysteine has been purported to have anti-inflammatory properties. Materials and methods: 34 albino Wistar rats were used. The model of gastritis was induced by subcutaneous Indomethacin prepared in 5% sodium bicarbonate administered at a dose rate of 9 mg/kg for two days at 24h intervals. N-acetylcysteine (500 mg/kg), Amlodipine (10 mg/kg) and N-acetylcysteine (500 mg/kg) combined with Amlodipine (5 mg/kg) were administrated for seven consecutive days beginning 24 h after the first Indomethacin injection. Rats were sacrificed under ether anesthesia on the 8th day. The stomach injury was assessed by macroscopic damage and histological study. Results and discussion: The results showed that macroscopic stomach damage scores caused by administration of Indomethacin did not significantly decrease by administration of N-acetylcysteine alone (p>0.05), but it decreased significantly by administration of Amlodipine alone or by its combination with N-acetylcysteine (p<0.05). Microscopic stomach damage scores did not significantly decrease by administration of Amlodipine or N-acetylcysteine alone (p>0.05), but they decreased significantly by administering the combination of Amlodipine with N-acetylcysteine (p<0.05). Administration of Amlodipine with N-acetylcysteine showed significant reduction in the severity of the gastric inflammation induced by Indomethacin, which was evidenced macroscopically and microscopically. Conclusion: This study concluded that administration of Amlodipine with N-acetylcysteine produce obvious enhancement in gastritis induced by Indomethacin. Graphical abstract: