Volume 28, Issue 2 (July 2024)                   Physiol Pharmacol 2024, 28(2): 169-179 | Back to browse issues page

XML Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Mostafapour A, Asgharzadeh F, Nazari S E, Eskandari M, Naghibzadeh N, baharara J, et al . The evaluation of synergistic effects of combination therapy with sulfasalazine and angiotensin-converting enzyme inhibitor in the treatment of experimental colitis in mice. Physiol Pharmacol 2024; 28 (2) : 7
URL: http://ppj.phypha.ir/article-1-2123-en.html
Abstract:   (596 Views)

Introduction: Intestinal colitis, also known as ulcerative colitis, is an inflammatory bowel disease characterized by long-term inflammation and ulcers in the gastrointestinal tract. It has been suggested that the mucosal expression of angiotensin II (AT-II) is increased in colitis. This study aimed to examine the potential therapeutic effects of combination therapy with Enalapril, an angiotensin-converting enzyme inhibitor, and sulfasalazine (SSZ) in a murine colitis model.
Methods: Male C57BL/6 mice were divided into five groups: control group (distilled water), dextran sulphate sodium (DSS) group (colitis group) (1% DSS), SSZ group (positive control group) with 100 mg/kg/day, Enalapril alone group with 4 mg/kg/day, and Enalapril (4 mg/kg/day) + SSZ (100 mg/kg/day) group.
Results: There was a significant reduction in the disease activity index among the mice receiving the combination of Enalapril and SSZ compared to the colitis group. Enalapril and SSZ treatment was associated with a lower reduction in colon length, decreased colon weight, spleen weight, and spleen-to-body weight in mice with colitis. Following DSS administration, Enalapril and SSZ also significantly decreased MDA levels, an oxidant marker, and increased total thiol, SOD, and CAT levels, as antioxidants. Additionally, mucosal damage, crypt loss, pathological changes, and inflammation scores decreased after treatment with Enalapril and SSZ in comparison with the colitis group. The combination of Enalapril and SSZ reduced colon collagen content and caused a decrease in fibrosis compared to the colitis group.
Conclusion: The results of this study indicated that Enalapril alone and in combination with SSZ decreased inflammation and clinical symptoms of colitis induced by DSS.

Article number: 7
Full-Text [PDF 1624 kb]   (19 Downloads)    

1. Alican I, Şener G, Yüksel M, Gedik N, Ercan F, Jahovic N. The effect of angiotensin-converting enzyme inhibitors on experimental colitis in rats. Regulatory Peptides 2005; 130:67-74. [DOI:10.1016/j.regpep.2005.03.009]
2. Amidon S, Brown J E, Dave V S. Colon-targeted oral drug delivery systems: design trends and approaches. Aaps Pharmscitech 2015; 16: 731-741. [DOI:10.1208/s12249-015-0350-9]
3. Asgharzadeh F, Yaghoubi A, Nazari S E, Hashemzadeh A, Hasanian S M, Avan A, et al. The beneficial effect of combination therapy with sulfasalazine and valsartan in the treatment of ulcerative colitis. EXCLI Journal 2021; 20: 236.
4. Beniwal-Patel P, Shaker R. Gastrointestinal and liver disorders in women’s health: A point of care clinical guide: Springer, 2019. [DOI:10.1007/978-3-030-25626-5]
5. Bordoni L, Fedeli D, Nasuti C, Maggi F, Papa F, Wabitsch M, et al. Antioxidant and anti-inflammatory properties of Nigella sativa oil in human pre-adipocytes. Antioxidants 2019; 8: 51. [DOI:10.3390/antiox8020051]
6. Chassaing B, Aitken J D, Malleshappa M, Vijay-Kumar M. Dextran sulfate sodium (DSS)-induced colitis in mice. Current Protocols in Immunology 2014; 104: 15.25. 1-15.25. 14. [DOI:10.1002/0471142735.im1525s104]
7. Feagan B G, MacDonald J K. Oral 5-aminosalicylic acid for induction of remission in ulcerative colitis. Cochrane Database of Systematic Reviews 2012. [DOI:10.1002/14651858.CD000543.pub3]
8. Flynn S, Eisenstein S. Inflammatory bowel disease presentation and diagnosis. Surgical Clinics of North America 2019; 99: 1051-62. [DOI:10.1016/j.suc.2019.08.001]
9. Garg M, Royce S G, Tikellis C, Shallue C, Batu D, Velkoska E, et al. Imbalance of the renin-angiotensin system may contribute to inflammation and fibrosis in IBD: a novel therapeutic target? Gut 2020; 69: 841-851. [DOI:10.1136/gutjnl-2019-318512]
10. Ghafouri Z, Seyyedian S, Nikbakht J, Kouhsari E, Bayat S, Zargar H, et al. Effect of Sodium Cromoglycate on acetic acid-induced ulcerative colitis in mice. Korean Journal of Gastroenterology 2020; 75: 39-45. [DOI:10.4166/kjg.2020.75.1.39]
11. Haendeler J, Ishida M, Hunyady L, Berk B C. The third cytoplasmic loop of the angiotensin ii type 1 receptor exerts differential effects on extracellular signal-regulated kinase (ERK1/ERK2) and apoptosis via Ras-and Rap1-dependent pathways. Circulation Research 2000; 86: 729-736. [DOI:10.1161/01.RES.86.7.729]
12. Hamer H M, Jonkers D M, Vanhoutvin S A, Troost F J, Rijkers G, de Bruïne A, et al. Effect of butyrate enemas on inflammation and antioxidant status in the colonic mucosa of patients with ulcerative colitis in remission. Clinical Nutrition 2010; 29: 738-744. [DOI:10.1016/j.clnu.2010.04.002]
13. Hamza S M, Dyck J R. Systemic and renal oxidative stress in the pathogenesis of hypertension: modulation of long-term control of arterial blood pressure by resveratrol. Frontiers in Physiology 2014; 5: 292. [DOI:10.3389/fphys.2014.00292]
14. Hashemzehi M, Naghibzadeh N, Asgharzadeh F, Mostafapour A, Hassanian S M, Ferns G A, et al. The therapeutic potential of losartan in lung metastasis of colorectal cancer. EXCLI Journal 2020; 19: 927.
15. Heidari M, Hashemi S M, Baghaei K, Zali M R Z M. Comparative effects of different doses of dextran sodium sulfate on the induction of chronic colitis in C57BL/6 mice. Research in Medicine 2020; 44: 346-351.
16. Husain K, Edu Suarez A I, Hernandez W, Ferder L. Effect of paricalcitol and enalapril on renal inflammation/oxidative stress in atherosclerosis. World Journal of Biological Chemistry 2015; 6: 240. [DOI:10.4331/wjbc.v6.i3.240]
17. Kumar S D, Mutlu E A. What do I do with my medications if I become Pregnant? Safety of IBD medications during pregnancy. Inflammatory Bowel Disease: Springer, 2015: 171-187. [DOI:10.1007/978-3-319-14072-8_23]
18. Lee C, Chun J, Hwang S W, Kang S J, Im J P, Kim J S. Enalapril inhibits nuclear factor-κB signaling in intestinal epithelial cells and peritoneal macrophages and attenuates experimental colitis in mice. Life Sciences 2014; 95: 29-39. [DOI:10.1016/j.lfs.2013.11.005]
19. Lee S Y, Hur S J. Effect of treatment with peptide extract from beef myofibrillar protein on oxidative stress in the brains of spontaneously hypertensive rats. Foods 2019; 8: 455. [DOI:10.3390/foods8100455]
20. Moum B. Which are the 5-ASA compound side effects and how is it possible to avoid them? Inflammatory bowel diseases 2008; 14: S212-S213. [DOI:10.1002/ibd.20712]
21. Nikfar S, Rahimi R, Rezaie A, Abdollahi M. A meta-analysis of the efficacy of sulfasalazine in comparison with 5-aminosalicylates in the induction of improvement and maintenance of remission in patients with ulcerative colitis. Digestive Diseases and Sciences 2009; 54: 1157-1170. [DOI:10.1007/s10620-008-0481-x]
22. Perše M, Cerar A. Dextran sodium sulphate colitis mouse model: traps and tricks. Journal of Biomedicine and Biotechnology 2012; 2012. [DOI:10.1155/2012/718617]
23. Rieder F, Bettenworth D, Ma C, Parker C E, Williamson L A, Nelson S A, et al. An expert consensus to standardise definitions, diagnosis and treatment targets for anti-fibrotic stricture therapies in Crohn’s disease. Alimentary pharmacology & therapeutics 2018; 48: 347-357. [DOI:10.1111/apt.14853]
24. Shi Y, Liu T, He L, Dougherty U, Chen L, Adhikari S, et al. Activation of the renin-angiotensin system promotes colitis development. Scientific Reports 2016; 6: 1-11. [DOI:10.1038/srep27552]
25. Spencer A U, Yang H, Haxhija E Q, Wildhaber B E, Greenson J K, Teitelbaum D H. Reduced severity of a mouse colitis model with angiotensin converting enzyme inhibition. Digestive Diseases and Sciences 2007; 52: 1060-1070. [DOI:10.1007/s10620-006-9124-2]
26. Sueyoshi R, Ignatoski K M W, Daignault S, Okawada M, Teitelbaum D H. Angiotensin converting enzyme-inhibitor reduces colitis severity in an IL-10 knockout model. Digestive Diseases and Sciences 2013; 58: 3165-3177. [DOI:10.1007/s10620-013-2825-4]
27. Sutherland L R, MacDonald J K. Oral 5-aminosalicylic acid for maintenance of remission in ulcerative colitis. Cochrane Database of Systematic Reviews 2006. [DOI:10.1002/14651858.CD000544.pub2]
28. Takahashi M, Suzuki E, Takeda R, Oba S, Nishimatsu H, Kimura K, et al. Angiotensin II and tumor necrosis factor-α synergistically promote monocyte chemoattractant protein-1 expression: roles of NF-κB, p38, and reactive oxygen species. American Journal of Physiology-Heart and Circulatory Physiology 2008; 294: H2879-H2888. [DOI:10.1152/ajpheart.91406.2007]
29. Walker A M, Szneke P, Bianchi L A, Field L G, Sutherland L R, Dreyer N A. 5-Aminosalicylates, sulfasalazine, steroid use, and complications in patients with ulcerative colitis. American Journal of Gastroenterology (Springer Nature) 1997; 92.
30. Wang L-X, Ideishi M, Yahiro E, Urata H, Arakawa K, Saku K. Mechanism of the cardioprotective effect of inhibition of the renin-angiotensin system on ischemia/reperfusion-induced myocardial injury. Hypertension Research 2001; 24: 179-187. [DOI:10.1291/hypres.24.179]
31. Wengrower D, Zannineli G, Pappo O, Latella G, Sestieri M, Villanova A, et al. Prevention of fibrosis in experimental colitis by captopril: The role of TGF-β1. Inflammatory Bowel Diseases 2004; 10: 536-545. [DOI:10.1097/00054725-200409000-00007]

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.