JBM  Vol.5 No.8 , August 2017
Trivalent Chromium Promotes Healing of Experimental Colitis in Mice by Suppression of Inflammation and Oxidative Stress
Abstract: Ulcerative colitis (UC) has reactive oxygen species (ROS) and immunologic pathways implicated in its pathogenesis. The search for new therapeutic protocols in managing UC is tailored in suppressing or preventing these pathways. The influence of trivalent chromium (Cr3+), an essential mineral on experimental colitis was investigated. Mice were grouped into 3; group 1 (control) received clean drinking water while groups 2 and 3 received 10 and 100 ppm Cr3+ respectively for 12 weeks through drinking water. After Cr3+ administration, 5 animals per group were sacrificed on day 0. Thereafter, experimental colitis was induced intra-rectally using acetic acid (4%, 0.3mL) and 5 mice per group were subsequently sacrificed on days 3, 7 and 14. Blood and colonic tissues were obtained and processed appropriately. Blood Cr3+ level, haematological variables, gross and microscopic colitis scores, colonic myeloperoxidase (MPO), Superoxide Dismutase (SOD) and malondialdehyde (MDA) levels were determined using standard methods. Colon cytokine mRNA genes were quantified using real-time PCR. There was a significant decrease in colon gross and histology scores on days 3 and 7 in chromium treated compared with control. The MPO and MDA in chromium groups reduced significantly compared with control while SOD activities increased significantly in Cr3+ groups compared with control. Total RNA increased in chromium groups compared with control on day 3 post-colitis. There was up-regulation of IL-10, down-regulation of TNF-α and IFN-λ in chromium administered groups compared with control. Chromium enhanced healing of colitis by suppression of ROS, inflammation and promotion of antioxidant activities.
Cite this paper: Odukanmi, O. , Salami, A. , Koda, K. , Morakinyo, O. and Olaleye, S. (2017) Trivalent Chromium Promotes Healing of Experimental Colitis in Mice by Suppression of Inflammation and Oxidative Stress. Journal of Biosciences and Medicines, 5, 108-126. doi: 10.4236/jbm.2017.58009.

[1]   Abraham, C. and Medzhitov, R. (2011) Interactions between the Host Innate Immune System and Microbes in Inflammatory Bowel Disease. Gastroenterology, 140, 1729-1737.

[2]   Keshavarzian, A., Morgan, G., Sedghi, S., Gordon, J.H. and Doria, M. (1990) Role of Reactive Oxygen Metabolites in Experimental Colitis. Gut, 31, 786-790.

[3]   Grisham, M.B. (1994) Oxidant and Free Radicals in Inflammatory Bowel Disease. Lancet, 344, 859-861.

[4]   Millar, A.D., Rampton, D.S., Chander, C.L., Claxson, A.W., Blades. S., Coumbe, A. et al. (1996) Evaluating the Antioxidant Potential of New Treatments for Inflammatory Bowel Disease Using a Rat Model of Colitis. Gut, 39, 407-415.

[5]   Fiocchi, C. (1998) Inflammatory Bowel Disease: Etiology and Pathogenesis. Gastroenterology, 115, 182-205.

[6]   Podolsky, D.K. (2002) Inflammatory Bowel Disease. New England Journal of Medicine, 347, 417-429.

[7]   Nosal’ova, V., Cerna, S. and Bauer, V. (2000) Effect of N-Acetylcysteine on Colitis Induced by Acetic Acid in Rats. General Pharmacology, 35, 77-81.

[8]   Kanodia, L., Borgohain, M. and Das, S. (2011) Effect of Fruit Extract of Fragaria vesca Leave on Experimentally Induced Inflammatory Bowel Disease in Albino Rats. Indian Journal of Pharmacology, 43, 118-121.

[9]   National Institute of Health (NIH) (2013) Chromium Dietary Supplement Facts Sheet. National Institute of Health, Bethesda, 1-7.

[10]   Mertz, W. (1993) Chromium in Human Nutrition: A Review. Journal of Nutrition, 123, 626-633.

[11]   Mertz, W. (1998) Interaction of Chromium with Insulin: A Progress Report. Nutritional Review, 56, 174-177.

[12]   Stoecker, B.J. (2001) Chromium. In: Bowman, B. and Russell, R., Eds., Present Knowledge in Nutrition, 8th Edition, ILSI Press, Washington DC, 366-372.

[13]   Vincent, J.B. (2003) The Potential Value and Toxicity of Chromium Picolinate as a Nutritional Supplement, Weight Loss Agent and Muscle Development Agent. Sports Medicine, 33, 213-230.

[14]   National Institute of Health Publication (1996) Guide for the Care and Use of Laboratory Animals. Revised No. 85-23.

[15]   Choudhary, J., Blackstock, W., Creasy, D. and Cottrell, J. (2001) Matching Peptide Mass Spectra to EST and Genomic DNA Databases. Trends Biotechnology, 19, S17-S22.

[16]   Fukuda, R., Hirota, K., Fan, F., et al. (2002) Insulin-Like Growth Factor 1 Induces Hypoxia-Inducible Factor 1-Mediated Vascular Endothelial Growth Factor Expression, Which Is Dependent on MAP Kinase and Phosphatidylinositol 3-Kinase Signaling in Colon Cancer Cell. The Journal of Biological Chemistry, 277, 38205-38211.

[17]   Morris, G.P., Beck, P.L., Herrigge, M.S., et al. (1989) Hapten Induced Model of Chronic Inflammation and Ulceration in the Rat Colon. Gastroenterology, 96, 795-803.

[18]   Varshney, R. and Kale, R.K. (1990) Effect of Calmodulin Antagonists on Radiation Induced Lipid Peroxidation in Microsomes. International Journal of Biology, 158, 733-741.

[19]   Sinha, K.A. (1972) Colorimetric Assay of Catalase. Analytical Biochemistry, 47, 389-394.

[20]   Misra, H.P. and Fridovich, I. (1972) The Role of Superoxide Anion in the Autoxidation of Epinephrine and a Simple Assay for Superoxide Dismutase. Journal of Biological Chemistry, 25, 3170-3175.

[21]   Ignarro, L.J., Buga, G.M., Wood, K.S., et al. (1987) Endothelium-Derived Relaxing Factor Produced and Released from Artery and Vein Is Nitric Oxide. Proceedings of National Academy of Sciences, 84, 9265-9269.

[22]   Griess, P. (1879) Bemerkungen zu der abhandlung der H.H., Weselsky und Benedikt. “Ueber einige azoverbindungen.” Chemische Berichte, 12, 426-428.

[23]   Kim, J.J., Shajib, M.S., Manocha, M.M., et al. (2012) Investigating Intestinal Inflammation in DSS-Induced Model of IBD. Journal of Visual Experiments, 60, e3678.

[24]   Elson, C.O., Sartor, R.B., Tennyson, G.S. and Riddell, H. (1995) Experimental Models of Inflammatory Bowels Disease. Gastroenterology, 109, 1344.

[25]   Smyth, S.S., McEver, R.P., Weyrich, A.S., et al. (2009) Platelet Colloquium Participants. Platelet Functions beyond Hemostasis. Journal of Thrombosis Haemostasis, 7, 1759-1766.

[26]   Morrell, C.N., Aggrey, A.A., Chapman, L.M. and Modjeski, K.L. (2014) Emerging Roles for Platelets as Immune and Inflammatory Cells. Blood, 123, 2759-2767.

[27]   Lih-Brody, L. Powell, S.R., Collier, K.P., et al. (1996) Increased Oxidative Stress and Decreased Antioxidant Defenses in Mucosa of Inflammatory Bowel Disease. Digestive Diseases and Sciences, 41, 2078-2086.

[28]   Thomson, A., Hemphill, D. and Jeejeebhoy, K.N. (1998) Oxidative Stress and Antioxidants in Intestinal Disease. Digestive Diseases and Sciences, 16, 152-158.

[29]   Bhattacharyya, A., Chattopadhyay, R., Mitra, S. and Crowe, S.E. (2014) Oxidative Stress: An Essential Factor in the Pathogenesis of Gastrointestinal Mucosal Diseases. Physiological Reviews, 94, 329-354.

[30]   Iles, K.E., Dickinson, D.A., Watanabe, N., et al. (2002) AP-1 Activation through Endogenous H2O2 Generation by Alveolar Macrophages. Free Radical Biology and Medicine, 32, 1304-1313.

[31]   Pechova, A. and Pavlata, L. (2007) Chromium as an Essential Nutrient: A Review. Veterinarni Medicina, 52, 1-18.

[32]   Okada, S., Tsukada, H. and Ohba, H. (1983) Enhancement of Ribonucleic Acid Synthesis by Chromium (III) in Regeneratin Rat Liver. Journal of Inorganic Biochemistry, 19, 95-103.

[33]   Deisenroth, C. and Zhang, Y. (2010) Ribosome Bio-genesis Surveillance: Probing the Ribosomal Protein Mdm2-p53 Pathway Oncogene. Epub, 29, 204253-204260.

[34]   Steffen, K.K., McCormick, M.A., Pham, K.M., et al. (2012) Ribosome Deficiency Protects against ER Stress in Saccharomyces cerevisiae. Genetics, 191, 107-118.

[35]   Wan, W., Lim, J.K., Lionakis, M.S., et al. (2011) Genetic Deletion of Chemokine Receptor Ccr6 Decreases Atherogenesis in ApoE-Deficient Mice. Circulatory Research, 109, 374-381.

[36]   Wier, E.M., Neighoff, J., Sun, X., et al. (2012) Identification of an N-Terminal Truncation of the NF-Kappa B p65 Subunit That Specifically Modulates Ribosomal Protein S3-Dependent NF-kappaB Gene Expression. The Journal of Biological Chemistry, 287, 430.

[37]   Yang, H.J., Youn, H., Seong, K.M., et al. (2013) Phosphorylation of Ribosomal Protein S3 and Antiapoptotic TRAF2 Protein Mediates Radio Resistance in Non-Small Cell Lung Cancer Cells. Journal of Biological Chemistry, 288, 2965-2975.

[38]   Tsirogianni, A.K., Moutsopoulos, N.M. and Moutsopoulos, H.M. (2006) Wound Healing: Immunological Aspects. Injury, 375, S5-S12.

[39]   WanYong, H., Huynh, K.Y., Swee, K.Y., et al. (2009) Traditional Practice, Bioactivities and Commercialization Potential of Elephantopus scaber Linn. Journal of Medicinal Plant Research, 3, 1212-1221.

[40]   Cheville, N.F. (1999) Introduction to Veterinary Pathology. 2nd Edition, Iowa State University Press, Ames, 118-119.

[41]   Vitarbo, E.A., Chatzipanteli, K., Kinoshita, K., et al. (2004) TNF Expression and Protein Levels Following Fluid Percussion Injury in Rats: The Effect of Injury Severity and Brain Temperature. Neurosurgery, 55, 416-425.

[42]   Seno, H., Miyoshi, H., Brown, S.L., et al. (2009) Efficient Colonic Mucosal Wound Repair Requires Trem2 Signaling. Proceedings of National Academy of Sciences, 106, 256-261.

[43]   Goresky, T., Dirisina, R., Sinh, P., et al. (2012) p53 Mediates TNF-Induced Epithelial Cell Apoptosis in IBD. American Journal of Pathology, 181, 1306-1315.

[44]   Fan, L., Young, P.R., Barone, F.C., et al. (1996) Experimental Brain Injury Induces Differential Expression of Tumor Necrosis Factor-Alpha mRNA in the CNS. Brain Research. Molecular Brain Research, 36, 287-291.

[45]   Knoblach, S.M., Fan, L. and Faden, A.I. (1999) Early Neuronal Expression of Tumor Necrosis Factor after Experimental Brain Injury Contributes to Neurological Impairment. Journal of Neuroimmunology, 95, 115-125.