MOLECULAR, HISTOLOGICAL, AND ANTI-OXIDANT EVALUATION OF COLITIS INDUCTION IN RATS BY DIFFERENT CONCENTRATION OF DEXTRAN SODIUM SULFATE (5 KDA)
Objective: Â The current study was conceived and performed to assess the pathophysiological, histological, and molecular manipulations of dextran sodium sulphate (DSS; MW: 5,000 Da) intervention in the rat and determined the changes in the antioxidant capacity of host and representative antioxidant enzymes.
Methods: Wistar rats were fed with two different concentrations (3 and 5%) of DSS for seven days and caged for another seven days. Then colon and serum samples were collected, and colitis induction was assessed by histochemical examination. The level of antioxidant enzymes were determined by spectroscopy methods, and gene regulations were evaluated by qPCR.
Results: The body mass of rat was gradually reduced to DSS intervention compared to naive control. The statistically significant level of reduction in the colon length has been recorded in DSS-treated rats (3% DSS-treated: 14.33Â±0.53 cm; 5% DSS-treated: 13.73Â±0.53 cm) compared to control (Control: 17.41Â±0.54 cm). The total histological scores of different study groups suggested that DSS causes the significant level of damages in rat colon. The antioxidant capacity of the host was significantly reduced in terms of trolox equivalence. About three-fold higher the amount of malondialdehyde was recorded in 5% DSS-treated group compared to control. The content of antioxidant enzymes were drastically reduced (1.4-2.7 fold) upon DSS exposure than naÃ¯ve control. The expression of selected inflammatory markers (IL-6, TNF-Î±, and iNOS) was up-regulated in DSS-exposed groups.
Conclusion: The current study clearly indicated that DSS altered the expression of selected inflammatory genes, antioxidant capacity, and scavenging enzymes in such a way that it facilitates the development of colitis in Wistar rat and the study provides the necessary information the experimental designing to explore the ability of any active principle against colitis using DSS (5 KDa) induced colitis rat model.
2. Danese S, Malesci A, Vetrano S. Colitis-associated cancer: the dark side of inï¬‚ammatory bowel disease. Gut 2011;60:1609-10.
3. Strober W. Animal models in inflammatory bowel disease and overview. Dig Dis Sci 1985;30:3S-10S.
4. Alex P, Zachos NC, Nguyen T, Gonzales L, Chen TE, Conklin LS, et al. Distinct cytokine patterns identified from multiplex profiles of murine DSS and TNBS-induced colitis. Inflammatory Bowel Dis 2009;15:341-52.
5. Solomon L, Mansor S, Mallon P, Donnelly E, Hoper M, Loughrey M, et al. The dextran sulphate sodium (DSS) model of colitis: an overview. Comp Clin Pathol 2010;19:235-9.
6. Randhawa PK, Singh K, Singh N, Jaggi AS. A Review on chemical-induced inflammatory bowel disease models in rodents. Korean J Physiol Pharmacol 2014;18:279-88.
7. Gaudio E, Taddei G, Vetuschi A, Sferra R, Frieri G, Ricciardi G, et al. Dextran sulfate sodium (dss) colitis in rats: clinical, structural, and ultrastructural aspects. Dig Dis Sci 1999;44:1458-75.
8. Kullmann F, Messmann H, Alt M, Gross V, Bocker T, Scholmerich J, et al. Clinical and histopathological features of dextran sulfate sodium-induced acute and chronic colitis-associated with dysplasia in rats. Int J Colorectal Dis 2001;16:238-46.
9. Mallon PT, Mckenna M, Kirk SJ, Gardiner KR. Dextran sulfate sodium (DSS) induced colitis reduces mucosal barrier function in Sprague-Dawley rats. Canadian Digestive Diseases Week, Alberta [Canada]: Canadian Association of Gastroenterology; 2006.
10. Van Meeteren ME, Meijssen MA, Zijlstra FJ. The effect of dexamethasone treatment on murine colitis. Scand J Gastroenterol 2000;35:517-21.
11. Shichijo K, Gottfried M, Sekine I, Pappas TN. Dextran sulfates sodium-induced colitis in immunodeficient rats. Dig Dis Sci 2000;45:2320-6.
12. Kitajima S, Takuma S, Morimoto M. Histological analysis of murine colitis induced by dextran sulfate sodium of different molecular weights. Exp Anim 2000;49:9-15.
13. Shimizu T, Suzuki M, Fujimura J, Hisada K, Yoshikazu O, Obinata K, et al. The relationship between the concentration of dextran sodium sulfate and the degree of induced experimental colitis in weanling rats. J Pediatr Gastroenterol Nutr 2003;37:481-6.
14. Aoi Y, Terashima S, Ogura M, Nishio H, Kato S, Takeuchi K. Role of nitric oxide (NO) and No synthases in the healing of dextran sulfate sodium-induced rat colitis. J Physiol Pharmacol 2008;59:315-36.
15. Perse M, Cerar A. Dextran sodium sulphate colitis mouse model: traps and tricks. J Biomed Biotechnol 2012. doi.org/10.1155/2012/718617. [Article in Press]
16. Cooper HS, Murthy SN, Shah RS, Sedergran DJ. A clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest 1993;69:238-49.
17. Pengkumsri N, Chaiyasut C, Saenjum C, Sirilun S, Peerajan S, Suwannalert P, et al. Physicochemical and antioxidative properties of black, brown and red rice varieties of northern Thailand. Food Sci.Technol 2015;35:331-8.
18. Suwannalert P, Rattanachitthawat S, Chaiyasut C, Riengrojpitak S. High levels of 25-hydroxyvitamin D3[25(OH)D3] and Î±-tocopherol prevent oxidative stress in rats that consume Thai brown rice. J Med Plant Res 2010;4:120-4.
19. Yang H, Fan S, Song D, Wang Z, Ma S, Li S, et al. Long-term streptozotocin-induced diabetes in rats leads to severe damage of brain blood vessels and neurons via enhanced oxidative stress. Mol Med Rep 2013;7:431-40.
20. Basler M, Dajee M, Moll C, Groettrup M, Kirk JC. Prevention of experimental colitis by a selective inhibitor of the immunoproteasome. J Immunol 2010;185:634-41.
21. Laroui H, Ingersoll SA, Liu HC, Baker MT, Ayyadurai S, Charania MA, et al. Dextran sodium sulfate (DSS) induces colitis in mice by forming nano-lipocomplexes with medium-chain-length fatty acids in the colon. PLoS One 2012;7:e32084.
22. Wu LH, Xu ZL, Dong D, He SA, Yu H. Protective effect of anthocyanins extract from blueberry on TNBS-induced IBD model of mice. Evid Based Complement Alternat Med 2011:1-8. doi:10.1093/ecam/neq040. [Epub 2011 Apr 14]
23. Montrose DC, Horelik NA, Madigan JP, Stoner GD, Wang LS, Bruno RS, et al. Anti-inflammatory effects of freeze-dried black raspberry powder in ulcerative colitis. Carcinogenesis 2011;32:343-50.
24. Bhattacharyya S, Dudeja PK, Tobacman JK. ROS, Hsp27, and IKK beta mediate dextran sodium sulfate (DSS) activation of Ikappa Ba, NFkappa B, and IL-8. Inflammatory Bowel Dis 2009;15:673-83.
25. Yeom Y, Kim Y. The sasa quelpaertensis leaf extract inhibits the dextran sulfate sodium-induced mouse colitis through modulation of antioxidant enzyme expression. J Cancer Prev 2015;20:136-46.
26. Melgar S, Karlsson L, RehnstrÃ¶m E, Karlsson A, Utkovic H, Jansson L, et al. Validation of murine dextran sulfate sodium-induced colitis using four therapeutic agents for human inflammatory bowel disease. Int Immunopharmacol 2008;8:836-44.