DOI QR코드

DOI QR Code

Hyaluronic Acid Increases Anti-Inflammatory Efficacy of Rectal 5-Amino Salicylic Acid Administration in a Murine Colitis Model

  • Received : 2020.12.15
  • Accepted : 2021.04.27
  • Published : 2021.09.01

Abstract

5-amino salicylic acid (5-ASA) is a standard therapy for the treatment of mild to moderate forms of inflammatory bowel diseases (IBD) whereas more severe forms involve the use of steroids and immunosuppressive drugs. Hyaluronic acid (HA) is a naturally occurring non-sulfated glycosaminoglycan that has shown epithelium protective effects in experimental colitis recently. In this study, both 5-ASA (30 mg/kg) and HA (15 mg/kg or 30 mg/kg) were administered rectally and investigated for their potential complementary therapeutic effects in moderate or severe murine colitis models. Intrarectal treatment of moderate and severe colitis with 5-ASA alone or HA alone at a dose of 30 mg/kg led to a significant decrease in clinical activity and histology scores, myeloperoxidase activity (MPO), TNF-α, IL-6 and IL-1β in colitis mice compared to untreated animals. The combination of HA (30 mg/kg) and 5-ASA in severe colitis led to a significant improvement of colitis compared to 5-ASA alone. Combined rectal therapy with HA and 5-ASA could be a treatment alternative for severe cases of IBD as it was the only treatment tested that was not significantly different from the healthy control group. This study further underlines the benefit of searching for yet unexplored drug combinations that show therapeutic potential in IBD without the need of designing completely new drug entities.

Keywords

Acknowledgement

Henusha D. Jhundoo gratefully acknowledges the German Academic Exchange Service (Deutscher Akademischer Austauschdienst, DAAD) (91525759) for financial support. Alf Lamprecht is grateful to the support from a French Government grant managed by the French National Research Agency under the program "Investissements d'Avenir" with reference ANR-11-LABX-0021.

References

  1. Ade-Ajayi, N., Spitz, L., Kiely, E., Drake, D. and Klein, N. (1996) Intestinal glycosaminoglycans in neonatal necrotizing enterocolitis. Br. J. Surg. 83, 415-418. https://doi.org/10.1002/bjs.1800830339
  2. Akazawa, A., Sakaida, I., Higaki, S., Kubo, Y., Uchida, K. and Okita, K. (2002) Increased expression of tumor necrosis factor-alpha messenger RNA in the intestinal mucosa of inflammatory bowel disease, particularly in patients with disease in the inactive phase. J. Gastroenterol. 37, 345-353. https://doi.org/10.1007/s005350200048
  3. Altman, R. D. and Moskowitz, R. (1998) Intraarticular sodium hyaluronate (Hyalgan) in the treatment of patients with osteoarthritis of the knee: a randomized clinical trial. J. Rheumatol. 26, 1216.
  4. Balogh, L., Polyak, A., Mathe, D., Kiraly, R., Thuroczy, J., Terez, M., Janoki, G., Ting, Y., Bucci, L. R. and Schauss, A. G. (2008) Absorption, uptake and tissue affinity of high-molecular-weight hyaluronan after oral administration in rats and dogs. J. Agric. Food Chem. 56, 10582-10593. https://doi.org/10.1021/jf8017029
  5. Bhattacharya, J., Cruz, T., Bhattacharya, S. and Bray, B. A. (1989) Hyaluronan affects extravascular water in lungs of unanesthetized rabbits. J. Appl. Physiol. 66, 2595-2599. https://doi.org/10.1152/jappl.1989.66.6.2595
  6. Campo, G. M., Avenoso, A., Campo, S., D'Ascola, A., Traina, P., Sama, D. and Calatroni, A. (2008) NF-kB and caspases are involved in the hyaluronan and chondroitin-4-sulphate-exerted antioxidant effect in fibroblast cultures exposed to oxidative stress. J. Appl. Toxicol. 28, 509-517. https://doi.org/10.1002/jat.1302
  7. Chen, M., Li, L., Wang, Z., Li, P., Feng, F. and Zheng, X. (2019) High molecular weight hyaluronic acid regulates P. gingivalis-induced inflammation and migration in human gingival fibroblasts via MAPK and NF-κB signaling pathway. Arch. Oral Biol. 98, 75-80. https://doi.org/10.1016/j.archoralbio.2018.10.027
  8. Chinen, T., Komai, K., Muto, G., Morita, R., Inoue, N., Yoshida, H., Sekiya, T., Yoshida, R., Nakamura, K., Takayanagi, R. and Yoshimura, A. (2011) Prostaglandin E2 and SOCS1 have a role in intestinal immune tolerance. Nat. Commun. 2, 190. https://doi.org/10.1038/ncomms1181
  9. Chiu, C. T., Kuo, S. N., Hung, S. W. and Yang, C. Y. (2017) Combined treatment with hyaluronic acid and mesalamine protects rats from inflammatory bowel disease induced by intracolonic administration of trinitrobenzenesulfonic acid. Molecules 22, 904. https://doi.org/10.3390/molecules22060904
  10. Danese, S. and Fiocchi, C. (2011) Ulcerative colitis. N. Engl. J. Med. 365, 1713-1725. https://doi.org/10.1056/NEJMra1102942
  11. Dicker, K. T., Gurski, L. A., Pradhan-Bhatt, S., Witt, R. L., Farach-Carson, M. C. and Jia, X. (2014) Hyaluronan: a simple polysaccharide with diverse biological functions. Acta Biomater. 10, 1558-1570. https://doi.org/10.1016/j.actbio.2013.12.019
  12. Dillon, P. W., Keefer, K., Blackburn, J. H., Houghton, P. E. and Krummel, T. M. (1994) The extracellular matrix of the fetal wound: hyaluronic acid controls lymphocyte adhesion. J. Surg. Res. 57, 170-173. https://doi.org/10.1006/jsre.1994.1126
  13. Fiorino, G., Gilardi, D., Naccarato, P., Sociale, O. R. and Danese, S. (2014) Safety and efficacy of sodium hyaluronate (IBD98E) in the induction of clinical and endoscopic remission in subjects with distal ulcerative colitis. Dig. Liver Dis. 46, 330-334. https://doi.org/10.1016/j.dld.2013.12.008
  14. Hassan, M. S., Mileva, M. M., Dweck, H. S. and Rosenfeld, L. (1998) Nitric oxide products degrade chondroitin sulfates. Nitric Oxide 2, 360-365. https://doi.org/10.1006/niox.1998.0198
  15. Indaram, A. V., Visvalingam, V., Locke, M. and Bank, S. (2002) Mucosal cytokine production in radiation-induced proctosigmoiditis compared with inflammatory bowel disease. Am. J. Gastroenterol. 95, 1221-1225. https://doi.org/10.1016/S0002-9270(00)00805-4
  16. Jensen, E. C. (2013) Quantitative analysis of histological staining and fluorescence using ImageJ. Anat .Rec. 296, 378-381. https://doi.org/10.1002/ar.22641
  17. Jiang, D., Liang, J., Fan, J., Yu, S., Chen, S., Luo, Y., Prestwich, G. D., Mascarenhas, M. M., Garg, H. G., Quinn, D. A., Homer, R. J., Goldstein, D. R., Bucala, R., Lee, P. J., Medzhitov, R. and Noble, P. W. (2005) Regulation of lung injury and repair by Toll-like receptors and hyaluronan. Nat. Med. 11,1173-1179. https://doi.org/10.1038/nm1315
  18. Kim, Y. and de la Motte, C. A. (2020) The role of hyaluronan treatment in intestinal innate host defense. Front. Immunol. 11, 569. https://doi.org/10.3389/fimmu.2020.00569
  19. Krawisz, J. E., Sharon, P. and Stenson, W. F. (1984) Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Assessment of inflammation in rat and hamster models. Gastroenterology 87, 1344-1350. https://doi.org/10.1016/0016-5085(84)90202-6
  20. Lamprecht, A., Schafer, U. and Lehr C. M. (2001a) Size-dependent bioadhesion of micro- and nanoparticulate carriers to the inflamed colonic mucosa. Pharm. Res. 18, 788-793. https://doi.org/10.1023/A:1011032328064
  21. Lamprecht, A., Ubrich, N., Yamamoto, H., Schafer, U., Takeuchi, H., Maincent, P., Kawashima, Y. and Lehr, C. M. (2001b) Biodegradable nanoparticles for targeted drug delivery in treatment of inflammatory bowel disease. J. Pharmacol. Exp. Ther. 299, 775-781.
  22. Laurent, T. C., Dahl, I. M., Dahl, L. B., Engstrom-Laurent, A., Eriksson, S., Fraser, J. R., Granath, K. A., Laurent, C., Laurent, U. B., Lilja, K,, Pertoft, H., Smedsrod, B., Tengblad, A. and Wik, W. (1986) The catabolic fate of hyaluronic acid. Connect. Tissue Res. 15, 33-41. https://doi.org/10.3109/03008208609001971
  23. Marteau, P., Probert, C. S., Lindgren, S., Gassul, M., Tan, T. G., Dignass, A., Befrits, R., Midhagen, G., Rademaker, J. and Foldager, M. (2005) Combined oral and enema treatment with Pentasa (mesalazine) is superior to oral therapy alone in patients with extensive mild/moderate active ulcerative colitis: a randomised, double blind, placebo controlled study. Gut 54, 960-965. https://doi.org/10.1136/gut.2004.060103
  24. McCloy, R. A., Rogers, S., Caldon, C. E., Lorca, T., Castro, A. and Burgess, A. (2014) Partial inhibition of Cdk1 in G 2 phase overrides the SAC and decouples mitotic events. Cell Cycle 13, 1400-1412. https://doi.org/10.4161/cc.28401
  25. Moulari, B., Beduneau, A., Pellequer, Y. and Lamprecht, A. (2014) Lectin-decorated nanoparticles enhance binding to the inflamed tissue in experimental colitis. J. Control. Release 188, 9-17. https://doi.org/10.1016/j.jconrel.2014.05.046
  26. Murch, S. H., MacDonald, T. T., Walker-Smith, J. A., Levin, M., Lionetti, P. and Klein, N. J. (1993) Disruption of sulphated glycosaminoglycans in intestinal inflammation. Lancet 341, 711-714. https://doi.org/10.1016/0140-6736(93)90485-Y
  27. Neumann, A., Schinzel, R., Palm, D., Riederer, P. and Munch, G. (1999) High molecular weight hyaluronic acid inhibits advanced glycation endproduct-induced NF-kappaB activation and cytokine expression. FEBS Lett. 453, 283-287. https://doi.org/10.1016/S0014-5793(99)00731-0
  28. O'Neill, L. A. J. (2009) A feed-forward loop involving hyaluronic acid and toll-like receptor-4 as a treatment for colitis? Gastroenterology 137, 1889-1891. https://doi.org/10.1053/j.gastro.2009.10.015
  29. Safrankova, B., Gajdova, S. and Kubala, L. (2010) The potency of hyaluronan of different molecular weights in the stimulation of blood phagocytes. Mediators Inflamm. 2010, 380948. https://doi.org/10.1155/2010/380948
  30. Sturm, A. and Dignass, A. U. (2008) Epithelial restitution and wound healing in inflammatory bowel disease. World J. Gastroenterol. 14, 348-353. https://doi.org/10.3748/wjg.14.348
  31. Tesar, B. M., Jiang, D., Liang, J., Palmer, S. M., Noble, P. W. and Goldstein, D. R. (2006) The role of hyaluronan degradation products as innate alloimmune agonists. Am. J. Transplant. 6, 2622-2635. https://doi.org/10.1111/j.1600-6143.2006.01537.x
  32. Travis, S. P., Stange, E. F., Lemann, M., Oresland, T., Bemelman, W. A., Chowers, Y., Colombel, J. F., D'Haens, G., Ghosh, S., Marteau, P., Kruis, W., Mortensen, N. J., Penninckx, F. and Gassull, M.; European Crohn's and Colitis Organisation (ECCO) (2008) European evidence-based Consensus on the management of ulcerative colitis: current management. J. Crohns Colitis 2, 24-62. https://doi.org/10.1016/j.crohns.2007.11.002
  33. Volpi, N., Schiller, J., Stern, R. and Soltes, L. (2009) Role, metabolism, chemical modifications and applications of hyaluronan. Curr. Med. Chem. 16, 1718-1745. https://doi.org/10.2174/092986709788186138
  34. You, N., Chu, S., Cai, B., Gao, Y., Hui. M., Zhu, J. and Wang, M. (2020) Bioactive hyaluronic acid fragments inhibit lipopolysaccharide-induced inflammatory responses via the Toll-like receptor 4 signaling pathway. Front. Med. doi: 10.1007/s11684-020-0806-5 [Online ahead of print].
  35. Zheng, L., Riehl, T. E. and Stenson, W. F. (2009) Regulation of colonic epithelial repair in mice by Toll-like receptors and hyaluronic acid. Gastroenterology 137, 2041-2051. https://doi.org/10.1053/j.gastro.2009.08.055