Effect of Adrenomedullin Administration in Two Rat Models of Experimental Inflammatory Bowel Disease
American Journal of Life Sciences
Volume 3, Issue 3-2, May 2015, Pages: 39-42
Received: Mar. 29, 2015;
Accepted: Apr. 8, 2015;
Published: May 6, 2015
Views 4467 Downloads 130
Sayaka Nagata, Divivion of Circulatory and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
Tomomi Hikosaka, Divivion of Circulatory and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
Kazuo Kitamura, Divivion of Circulatory and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
Adrenomedullin (AM) is a novel hypotensive peptide that also exerts powerful anti-inflammatory effects. We recently showed that AM significantly reduces the clinical severity of acetic acid-induced colitis, an experimental model of inflammatory bowel disease (IBD) in rats. In the present study, we examined the effect of AM in two alternative rat models of IBD. We found that 2,4,6-trinitrobenzenesulfonic acid (TNBS) induced megacolon development in the saline-treated group, but AM treatment reduced the macroscopic damage caused by TNBS. In the dextran sulfate sodium (DSS) model, treatment with AM reduced diarrhea and bloody stool scores, but did not reduce body weight. Histological analysis revealed that in both the TNBS and DSS models, colon inflammation was much more severe in the saline-treated group than in the AM-treated group. These findings indicate that the anti-inflammatory properties of AM make it an effective therapeutic agent for the treatment of IBD in rats.
Effect of Adrenomedullin Administration in Two Rat Models of Experimental Inflammatory Bowel Disease, American Journal of Life Sciences. Special Issue:Biology and Medicine of Peptide and Steroid Hormones.
Vol. 3, No. 3-2,
2015, pp. 39-42.
Fiocchi, C. Inflammatory bowel disease: etiology and pathogenesis. Gastroenterology 115, 182-205 (1998).
Binion, D. G., West, G. A., Volk, E. E., Drazba, J. A., Ziats, N. P., Petras, R. E. Fiocchi, C. Acquired increase in leucocyte binding by intestinal microvascular endothelium in inflammatory bowel disease. Lancet 352, 1742-1746, doi:10.1016/S0140-6736(98)05050-8 (1998).
Salim, S. Y.Soderholm, J. D. Importance of disrupted intestinal barrier in inflammatory bowel diseases. Inflammatory bowel diseases 17, 362-381, doi:10.1002/ibd.21403 (2011).
Kitamura, K., Kangawa, K., Kawamoto, M., Ichiki, Y., Nakamura, S., Matsuo, H. Eto, T. Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma. Biochemical and biophysical research communications 192, 553-560, doi:10.1006/bbrc.1993.1451 (1993).
Kitamura, K., Kangawa, K. Eto, T. Adrenomedullin and PAMP: discovery, structures, and cardiovascular functions. Microscopy research and technique 57, 3-13, doi:10.1002/jemt.10052 (2002).
Ashizuka, S., Ishikawa, N., Kato, J., Yamaga, J., Inatsu, H., Eto, T. Kitamura, K. Effect of adrenomedullin administration on acetic acid-induced colitis in rats. Peptides 26, 2610-2615, doi:10.1016/j.peptides.2005.05.007 (2005).
Du, C., Wang, P., Yu, Y., Chen, F., Liu, J. Li, Y. Gadolinium chloride improves the course of TNBS and DSS-induced colitis through protecting against colonic mucosal inflammation. Scientific reports 4, 6096, doi:10.1038/srep06096 (2014).
Jakobsson, T., Vedin, L. L., Hassan, T., Venteclef, N., Greco, D., D'Amato, M., Treuter, E., Gustafsson, J. A. Steffensen, K. R. The oxysterol receptor LXRbeta protects against DSS- and TNBS-induced colitis in mice. Mucosal immunology 7, 1416-1428, doi:10.1038/mi.2014.31 (2014).
Alkahtani, R., Mahavadi, S., Al-Shboul, O., Alsharari, S., Grider, J. R. Murthy, K. S. Changes in the expression of smooth muscle contractile proteins in TNBS- and DSS-induced colitis in mice. Inflammation 36, 1304-1315, doi:10.1007/s10753-013-9669-0 (2013).
Beltowski, J.Jamroz, A. Adrenomedullin--what do we know 10 years since its discovery? Polish journal of pharmacology 56, 5-27 (2004).
Tache, Y. Inhibition of gastric acid secretion and ulcers by calcitonin [correction of calciton] gene-related peptide. Annals of the New York Academy of Sciences 657, 240-247 (1992).
Kaneko, H., Mitsuma, T., Nagai, H., Mori, S., Iyo, T., Kusugami, K. Tache, Y. Central action of adrenomedullin to prevent ethanol-induced gastric injury through vagal pathways in rats. The American journal of physiology 274, R1783-1788 (1998).
Clementi, G., Caruso, A., Cutuli, V. M., Mangano, N. G., Salomone, S., Lempereur, L., Prato, A., Matera, M. Amico-Roxas, M. Gastroprotective effect of adrenomedullin administered subcutaneously in the rat. Peptides 23, 1149-1153 (2002).
Maloy, K. J.Powrie, F. Intestinal homeostasis and its breakdown in inflammatory bowel disease. Nature 474, 298-306, doi:10.1038/nature10208 (2011).
Bain, C. C., Scott, C. L., Uronen-Hansson, H., Gudjonsson, S., Jansson, O., Grip, O., Guilliams, M., Malissen, B., Agace, W. W. Mowat, A. M. Resident and pro-inflammatory macrophages in the colon represent alternative context-dependent fates of the same Ly6Chi monocyte precursors. Mucosal immunology 6, 498-510, doi:10.1038/mi.2012.89 (2013).
Sakata, J., Asada, Y., Shimokubo, T., Kitani, M., Inatsu, H., Kitamura, K., Kangawa, K., Matsuo, H., Sumiyoshi, A. Eto, T. Adrenomedullin in the gastrointestinal tract. Distribution and gene expression in rat and augmented gastric adrenomedullin after fasting. Journal of gastroenterology 33, 828-834 (1998).
Kitani, M., Sakata, J., Asada, Y., Kitamura, K. Eto, T. Distribution and expression of adrenomedullin in human gastrointestinal tissue. Annals of clinical biochemistry 35 ( Pt 5), 643-648 (1998).
Hay, D. L.Smith, D. M. Adrenomedullin receptors: molecular identity and function. Peptides 22, 1753-1763 (2001).
McLatchie, L. M., Fraser, N. J., Main, M. J., Wise, A., Brown, J., Thompson, N., Solari, R., Lee, M. G. Foord, S. M. RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature 393, 333-339, doi:10.1038/30666 (1998).