SULFASALAZINE ATTENUATES ULCERATIVE COLITIS IN RATS VIA DOWNREGULATION OF MIRNA-31, METALLOPROTEINASE-3 AND HIGH MOBILITY GROUP BOX1

SYLVIA A. BOSHRA

doi:10.22159/ijpps.2021v13i8.41775

Authors

SYLVIA A. BOSHRA Biochemistry Department, Faculty of Pharmacy, October 6 University, Giza, Egypt

DOI:

https://doi.org/10.22159/ijpps.2021v13i8.41775

Keywords:

Dextran sodium sulfate, Leucine rich alpha 2 Glycoprotein, Trefoil Factor 3, Nuclear factor kappa B

Abstract

Objective: This study targets the inhibition of inflammatory mediators and the enhancement of gastrointestinal mucosa healing in ulcerative colitis in rats through sulfasalazine.

Methods: Twenty four female albino rats were divided into 3 groups: normal control, colitis group (rats received 5% dextran sodium sulfate (DSS) in their drinking water for 7 d), sulfasalazine group (500 mg/kg/day was administrated orally one week ahead of DSS and parallel with its administration). The impact of sulfasalazine on intestinal inflammation was investigated via estimation of some inflammatory mediators, namely; serum Leucine rich α 2 Glycoprotein (LRG) as well as colon cAMP, Myloperoxidase (MPO) and TNF-α using ELISA technique as well as gene expression of Trefoil Factor 3 (TFF3), High mobility group box1 (HMGB1), Nuclear factor kappa B (NF-κB) and metalloproteinase-3 (MMP3) and miRNA-31 levels using RT-PCR.

Results: Sulfasalazine substantially decreases the release of LRG, MPO and TNF-α and the expression of HMGB1, NF-κB, MMP3, TFF3 and miRNA31 at p≤ 0.05 compared to colitis group in vivo. Moreover, Sulfasalazine significantly increases the colonic cAMP at p≤ 0.05 in groups of rats treated with DSS.

Conclusion: Sulfasalazine has a protective effect on inflammatory bowel disease causing mucosal healing within the gastrointestinal tract. Additional studies are warranted to explore the molecular mechanism of sulfasalazine in ulcerative colitis and its clinical application.

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References

Gearry RB. IBD and environment are there differences between east and west. Dig Dis 2016;34:84–9.

Mshimesh B. Efficacy and safety of adalimumab versus infliximab in patients suffered from moderate to severe active ulcerative colitis. Asian J Pharm Clin Res 2017;10:300-7.

Monteleone G, Biancone L, Marasco R, Morrone O, Marasco O, Luzza F, et al. Interleukin 12 is expressed and actively released by Crohn’s disease intestinal lamina propria mononuclear cells. Gastroenterology 1997;112:1169-78.

Okayasu I, Hatakeyama S, Yamada M, Ohkusa T, Inagaki Y, Nakaya R. A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology 1990;98:694–702.

Thakur V, Singh B, Sharma A, Kumari N, Kumar I, Verma K, et al. Importance of nanocarriers and probiotics in the treatment of ulcerative colitis. Int J Appl Pharm 2021;13:77-85.

Mattam J, Sailaja K. Preparation and evaluation of sulfasalazine loaded sodium alginate microbeads for sustained delivery. Asian J Pharm Clin Res 2016;9:66-70.

Desreumaux P, Ghosh S. Review article: mode of action and delivery of 5-aminosalicylic acid–new evidence. Aliment Pharmacol Ther 2006;24:2-9.

Benoit C, Jesse D, Madhu M, Matam V. Dextran sulfate sodium (DSS)-induced colitis in mice. Curr Protoc Immunol 2014;25:1‐15.

Mi R, Kyeong J, Soo H, Su J, Bu I, Hyo J, et al. Comparative evaluation between sulfasalazine alone and in combination with herbal medicine on DSS-induced ulcerative colitis mice. BioMed Res Int 2017;3:1-10.

Arab HH, Al-Shorbagy MY, Abdallah DM, Nassar NN. Telmisartan attenuates colon inflammation, oxidative perturbations and apoptosis in a rat model of experimental inflammatory bowel disease. Plos One 2014;9:e97193.

Kawakami M, Kaneko N, Anada H. Measurement of interleukin-6, interleukin-10, and tumor necrosis factor-alpha levels in tissues and plasma after thermal injury in mice. Surgery 1997;121:440.

El-Ashmawy N, Khedr N, El-Bahrawy H, El-Adawy S. Roflumilast, type 4 phosphodiesterase inhibitor, attenuates inflammation in rats with ulcerative colitis via down-regulation of iNOS and elevation of cAMP. Int Immunopharmacol 1997;56:36-42.

Krawisz J, Sharon P, Stenson W. Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity: assessment of inflammation in rat and hamster models. Gastroenterology 1984;87:1344–50.

Lowry O, Rosebrough N, Farr A, Randall R. Protein measurement with the folin phenol reagent. J Biol Chem 1951;193:265–75.

Chen C, Ridzon DA, Broomer AJ, Zhou Z, Lee DH, Nguyen JT, et al. Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res 2005;33:e179.

Baumgart DC, Sandborn WJ. Inflammatory bowel disease: clinical aspects and established and evolving therapies. Lancet 2007;369:1641–57.

Gaya DR, Russell RK, Nimmo ER, Satsangi J. New genes in inflammatory bowel disease: lessons for complex diseases? Lancet 2006;367:1271–84.

Strober W, Murray PJ, Kitani A, Watanabe T. Signalling pathways and molecular interactions of NOD1 and NOD2. Nat Rev Immunol 2006;6:9–20.

Zhang ZL, Fan HY, Yang MY, Zhang ZK, Liu K. Therapeutic effect of a hydronaphthoquinone fraction on dextran sulfate sodium-induced ulcerative colitis. World J Gastroenterol 2014;20:15310-8.

Rogler G. Gastrointestinal and liver adverse effects of drugs used for treating IBD, best practice and research. Clin Gastroenterol 2010;24:157–65.

Buchheister S, Buettner M, Basic M. CD14 plays a protective role in experimental inflammatory bowel disease by enhancing intestinal barrier function. Am J Pathol 2017;187:1106–20.

Macfarlane S, Steed H, Macfarlane GT. Intestinal bacteria and inflammatory bowel disease. Crit Rev Clin Lab Sci 2009;46:25–54.

Kotlowski R, Bernstein CN, Sepehri S, Krause DO. High prevalence of Escherichia coli belonging to the B2+D phylogenetic group in inflammatory bowel disease. Gut 2007;56:669–75.

Braun A, Treede I, Gotthardt D, Tietje A, Zahn A, Ruhwald R. Alterations of phospholipid concentration and species composition of the intestinal mucus barrier in ulcerative colitis: a clue to pathogenesis. Inflamm Bowel Dis 2009;15:1705–20.

Rahimi R, Nikfar S, Rezaie A, Abdollahi MA. Meta-analysis of broad-spectrum antibiotic therapy in patients with active Crohn’s disease. Clin Ther 2006;28:1983–8.

Hoffmann W. Trefoil factors TFF (trefoil factor family) peptide-triggered signals promoting mucosal restitution. Cell Mol Life Sci 2005;62:2932–8.

Srivastava S, Kedia S, Kumar S, Mouli VP, Dhingra R, Sachdev V, et al. Serum human trefoil factor 3 is a biomarker for mucosal healing in ulcerative colitis patients with minimal disease activity. J Crohn's Colitis 2015;9:575–9.

Grønbaek H, Vestergaard EM, Hey H, Nielsen JN, Nexo E. Serum trefoil factors in patients with inflammatory bowel disease. Digestion 2006;74:33–9.

Wang KP, Zhang C, Zhang SG, Liu ED, Dong L, Kong XZ, et al. 3-(3-pyridylmethylidene)-2-indolinone reduces the severity of colonic injury in a murine model of experimental colitis. Oxid Med Cell Longev 2015. https://doi.org/10.1155/2015/959253

Islam MS, Murata T, Fujisawa M, Nagasaka R, Ushio H, Bari AM, et al. Anti-inflammatory effects of phytosteryl ferulates in colitis induced by dextran sulfate sodium in mice. Br J Pharmacol 2008;154:812-24.

Tahamtan A, Teymoori Rad M, Nakstad B, Salimi V. Anti-inflammatory microRNAs and their potential for inflammatory diseases treatment. Front Immunol 2018;9:1377.

Sylvia A. Boshra resveratrol modulates miR-34a in cardiotoxicity induced by isoproterenol. J Med Food 2020; 23:593–9.

Zheng L, Zhang YL, Dai YC, Chen X, Chen DL, Dai YT, et al. Jianpi qingchang decoction alleviates ulcerative colitis by inhibiting nuclear factor-κB activation. World J Gastroenterol 2017;23:1180-8.