EFFECT OF AMLODIPINE ON ENTEROPATHY INDUCED BY INDOMETHACIN IN RATS
Objective: Non-steroidal anti-inflammatory drugs (NSAIDs) have become well known for causing gastroduodenal mucosal damage. In addition, they are also known to affect the small intestine in humans. Amlodipine is a third-generation dihydropyridine-type calcium channel blocker; it can inhibit inflammatory cytokines and enhance antioxidant defenses. The aim of this study was to evaluate the effect of Amlodipine on indomethacin-induced enteropathy in rats.
Methods: Enteropathy was induced by subcutaneous indomethacin (Indo) prepared in 5 % sodium bicarbonate administrated at a dose rate of 9 mg/kg for two days at 24h intervals. Amlodipine (10 mg/Kg body weight po) was administrated for seven consecutive days beginning 24 h after the first Indo injection. Rats were sacrificed under ether anesthesia on the 8th day. The small intestinal injury was assessed by body weight loss, small intestine weight/length ratio, macroscopic damage, histological study, as well as by biochemical measurement of reduced glutathione (GSH), lipid peroxides and superoxide dismutase (SOD) activity in the small intestine tissue.
Results: The results showed that Amlodipine didn't decrease body weight loss, it decreased small intestine weight/length ratio, macroscopic and microscopic small intestinal damage scores caused by administration of Indo. It also increased SOD activity and decreased lipid peroxidation. The effect on the level of GSH wasn't observed. No statistical significance was observed when previous findings were compared to Indo induced enteropathy group (p>0.05).
Conclusion: Amlodipine didn't produce an obvious enhancement in enteropathy induced by Indo in rats.
2. Matsumoto T, Iida M, Nakamura S, Hizawa K, Kuroki F, Fujishima M. Preventive effect of immunosuppressive agents against indomethacin-induced small intestinal ulcers in rats. Dig Dis Sci 1994;39:787–95.
3. Lim YJ, Yang C. Non-steroidal anti-inflammatory drug-induced enteropathy. Clin Endosc 2012;45:138–44.
4. Graham DY, Opekun AR, Willingham FF, Qureshi WA. Visible small-intestinal mucosal injury in chronic NSAID users. Clin Gastroenterol Hepatol 2005;3565:55–9.
5. Takeuchi K. NSAID-induced small intestinal damage–roles of various pathogenic factors. Digestion 2015;91:218–32.
6. Park SC, Chun HJ, Kang CD, Sul D. Prevention and management of non-steroidal anti-inflammatory drug-induced small intestinal injury. World J Gastroenterol 2011;17:4647–53.
7. Tacheci I, Kopacova M, Rejchrt S, Bures J. Non-steroidal anti-inflammatory drug-induced injury to the small intestine. Acta Medica (Hradec Kralove) 2010;53:3–11.
8. Mohammed NEM, Messiha BAS, Abo-Saif AA. Effect of amlodipine, lisinopril and allopurinol on acetaminophen-induced hepatotoxicity in rats. Saudi Pharm J 2016;24:635–44.
9. El Morsy EM, Kamel R, Ahmed MAE. Attenuating effects of coenzyme Q10 and amlodipine in ulcerative colitis model in rats. Immunopharmacol Immunotoxicol 2015;37:244–51.
10. Jagtap AG, Shirke SS, Phadke AS. Effect of polyherbal formulation on experimental models of inflammatory bowel diseases. J Ethnopharmacol 2004;90:195–204.
11. Nakhai LA, Mohammadirad A, Yasa N, Minaie B, Nikfar S, Ghazanfari G, et al. Benefits of zataria multiflora boiss in an experimental model of mouse inflammatory bowel disease. Evidence Based Complement Altern Med 2007;4:43–50.
12. Moron MS, Depierre JW, Mannervik B. Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. BBA-Gen Sub 1979;582:67–78.
13. Li X. Improved pyrogallol autoxidation method: a reliable and cheap superoxide-scavenging assay suitable for all antioxidants. J Agric Food Chem 2012;60:6418–24.
14. Patil NR, Rasal VP, Malabade RH. Screening of mandarin oil on indomethcin induced inflammatory bowel disease in wistar rats. Indian J Pharm Educ Res 2014;48:1–6.
15. Kheradmand A, Alirezaei M, Asadian P, Rafiei Alavi E, Joorabi S. Antioxidant enzyme activity and MDA level in the rat testis following chronic administration of ghrelin. Andrologia 2009;41:335–40.
16. Reuter BK, Davies NM, Wallace JL. Nonsteroidal anti-inflammatory drug enteropathy in rats: role of permeability, bacteria, and enterohepatic circulation. Gastroenterology 1997;112:109–17.
17. Drees DT, Robbins TL, Crago FL. Effect of low-residue foods on lndomethacin-induced intestinal lesions in rats. Toxicol Appl Pharmacol 1974;27:194-9.
18. Elson OC, Sartor BR, Tennyson SG, Riddl HR. Experimental models of inflammatory bowel diseases. Gastroenterology 1995;109:1344-67.
19. Nandi J, Saud B, Zinkievich JM, Yang ZJ, Levine RA. TNF-? modulates iNOS expression in an experimental rat model of an indomethacin-induced jejunoileitis. Mol Cell Biochem 2010;336:17–24.
20. Yamada T, Deitch E, Specian DR, Perry AM, Sarto RrB, Grisham BM. Mechanisms of acute and crhonic intestinal inflammation induced by indomethacin. Inflammation 1993;17:641-62.
21. Kim YJ, Kim EH, Hahm KB. Oxidative stress in inflammation-based gastrointestinal tract diseases: challenges and opportunities. J Gastroenterol Hepatol 2012;27:1004–10.
22. Basivireddy J, Vasudevan A, Jacob M, Balasubramanian KA. Indomethacin-induced mitochondrial dysfunction and oxidative stress in villus enterocytes. Biochem Pharmacol 2002;64:339–49.
23. Kim K, Park J, Han Y, Lee SG, Shin SA. Azelnidipine, a novel calcium channel blocker, ameliorates severity of colitis in DSS induced colitis in DSS induced colitis in mice possibly by modulating tissue levels of TNF-alpha and IL-6. J Crohns Colitis 2017;11:29-30.
24. Rajinikanth B, Venkatachalam VV. Study on the effect of amlodipine on chemically induced inflammatory bowel disease using animal model. Int J PharmTech Res 2015;7:119–24.
25. Godfraind T. Antioxidant effects and the therapeutic mode of action of calcium channel blockers in hypertension and atherosclerosis. Philos Trans R Soc B Biol Sci 2005;360:2259–72.
26. Mahajan AS, Babbar R, Kansal N, Agarwal SK, Ray PC. Antihypertensive and antioxidant action of amlodipine and vitamin C in patients of essential hypertension. J Clin Biochem Nutr 2007;40:141–7.
27. Pronobesh C. Protective role of the calcium channel blocker amlodipine against mitochondrial injury in ischemia and reperfusion injury of rat liver 2008;58:421–8.
This work is licensed under a Creative Commons Attribution 4.0 International License.