Administration of Vitamin D3 Improves Hemoglobin Level by Regulating TNF-a and IL-6 in DSS-induced Colitis Mice

Ervin Monica, Primayuni Dhia Hasanah, Arief Fadillah, Rara Aulia, Eko Sulistijono, Satrio Wibowo

Abstract


BACKGROUND: Anemia is frequently found in ulcerative colitis (UC) patients and assumed to be related to inflammatory process. Vitamin D3 (VD) is known to have anti-inflammatory and immunomodulatory effects. It also has the potential to be an alternative treatment of the inflammatory process that occurs at UC, however its mechanism has not been clearly established. This study aimed to assess the effect of VD on histopathology and hemoglobin levels in UC through its regulation in tumor necrosis factor (TNF)-α and interleukin (IL)-6.

METHODS: Total samples of 24 mice were divided equally into Sham group, UC group, UC+VD group (given 3% dextran sodium sulfate (DSS) followed by VD), and VD+UC group (given VD followed by 3% DSS). Mouse Colitis Histology Index (MCHI) was used to measure histopathological changes. Immunohistochemical staining was used to observe expression of TNF-α and IL-6 in colon. Evaluation of anemia was determined by hemoglobin levels.

RESULTS: Based on MCHI scores, significant epithelial damage was found in colon sample of UC group (8.25±3.05) compared to Sham (0.33±0.26), UC+VD (2.33±1.07), and VD+UC group (2.83±0.75) (p<0.05). Significant lower numbers of TNF-α were found in Sham (27.33±3.42), UC+VD (36.33±1.86), and VD+UC group (36.68±1.86) compared with UC group (44.66±4.87) (p<0.05). Significant less IL-6 expression was found in Sham (18.05±2.96), UC+VD (24.78±0.79), and VD+UC group (25.09±2.79) compared to UC group (38.85±3.51) (p<0.05). Differences in hemoglobin levels were significantly lower in UC group (11.85±0.97) compared to Sham (14.25±0.47), UC+VD (13.68±0.68), VD+UC group (13.52±1.07) (p<0.05).

CONCLUSION: VD significantly reduced proinflammatory cytokines, increased mucosal repair, and improved hemoglobin levels.

KEYWORDS: colitis, ulcerative, interleukin-6, tumor necrosis factor-alpha


Full Text:

PDF

References


Randhawa PK, Singh K, Singh N, Jaggi AS. A review on chemicalinduced inflammatory bowel disease models in rodents. Korean J Physiol Pharmacol. 2014; 18: 279–88, CrossRef.

Mustika S, Triana N. The prevalence, profile, and risk factor of patients with ulcerative colitis at Dr. Saiful Anwar Malang General Hospital. Indones J Gastroenterol Hepatol Dig Endosc. 2016; 17: 16–20, CrossRef.

Basheer W, Kunde D, Eri R. Role of chemokine ligand CCL20 and its receptor CCR6 in intestinal inflammation. Immunol Infect Dis. 2013; 1: 30–7, CrossRef.

Antunes CV de A, Hallack Neto AE, Nascimento CR de A, Chebli LA, Moutinho ILD, Pinheiro B do V, et al. Anemia in inflammatory bowel disease outpatients: prevalence, risk factors, and etiology. Biomed Res Int. 2015; 2015: 728925, CrossRef.

Alves RA, Miszputen SJ, Figueiredo MS. Anemia in inflammatory bowel disease: prevalence, differential diagnosis and association with clinical and laboratory variables. Sao Paulo Med J. 2014; 132: 140–6, CrossRef.

Kaitha S, Bashir M, Ali T. Iron deficiency anemia in inflammatory bowel disease. World J Gastrointest Pathophysiol. 2015; 6: 62–72, CrossRef.

Ananthakrishnan AN, Khalili H, Konijeti GG, Higuchi LM, De Silva P, Korzenik JR, et al. A prospective study of long-term intake of dietary fiber and risk of Crohn’s disease and ulcerative colitis. Gastroenterology. 2013; 145: 970–7, CrossRef.

Abraham BP, Prasad P, Malaty HM. Vitamin D deficiency and corticosteroid use are risk factors for low bone mineral density in inflammatory bowel disease patients. Dig Dis Sci. 2014; 59: 1878–84, CrossRef.

AlSheikh MH, Almubayadh SI. Effect of vitamin D supplementation on insulin, fasting blood glucose, and waist-hip ratio in young females with pre-existing vitamin D deficiency. Indones Biomed J. 2019; 11: 42–7, CrossRef.

Lai YH, Fang TC. The pleiotropic effect of vitamin D. ISRN Nephrol. 2013; 2013: 898125, CrossRef.

Dai Z, Tan B, Yang H, Wang O, Qian JJ, Lv H. 1,25-hydroxyvitamin D relieves colitis in rats via downregulation of toll-like receptor 9 expression. Croat Med J. 2015; 56: 515–24, CrossRef.

Dionne S, Calderon MR, White JH, Memari B, Elimrani I, Adelson B, et al. Differential effect of vitamin D on NOD2-and TLR-induced cytokines in Crohn’s disease. Mucosal Immunol. 2014; 7: 1405–15, CrossRef.

Reich KM, Fedorak RN, Madsen K, Kroeker KI. Vitamin D improves inflammatory bowel disease outcomes: basic science and clinical review. World J Gastroenterol WJG. 2014; 20: 4934–47, CrossRef.

Zughaier SM, Alvarez JA, Sloan JH, Konrad RJ, Tangpricha V. The role of vitamin D in regulating the iron-hepcidin-ferroportin axis in monocytes. J Clin Transl Endocrinol. 2014; 1(1): e19–e25, CrossRef.

Koelink PJ, Wildenberg ME, Stitt LW, Feagan BG, Koldijk M, van‘t Wout AB, et al. Development of reliable, valid and responsive scoring systems for endoscopy and histology in animal models for inflammatory bowel disease. J Crohn’s Colitis. 2018; 12: 794–803, CrossRef.

Tulewicz-Marti E, Moniuszko A, Rydzewska G. Management of anemia in inflammatory bowel disease: a challenge in everyday clinical practice. Prz Gastroenterol. 2017; 12: 239–43, CrossRef.

Baumgart D, Baumgart DC. Crohn’s disease and ulcerative colitis. Switzerland: Springer; 2017, NLMID.

Rogler G, Vavricka S. Anemia in inflammatory bowel disease: an under-estimated problem? Front Med. 2015; 1: 58, CrossRef.

Wu-Wong JR. Potential for vitamin D receptor agonists in the treatment of cardiovascular disease. Br J Pharmacol. 2009; 158: 395–412, CrossRef.

Chen Y, Zhang J, Ge X, Du J, Deb DK, Li YC. Vitamin D receptor inhibits nuclear factor κB activation by interacting with IκB kinase β protein. J Biol Chem. 2013; 288: 19450–8, CrossRef.

Karimi S, Tabataba-vakili S, Yari Z, Alborzi F, Hedayati M, Ebrahimi-Daryani N, et al. The effects of two vitamin D regimens on ulcerative colitis activity index, quality of life and oxidant/anti-oxidant status. Nutr J. 2019;18: 16, CrossRef.

Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. N Engl J Med. 1987; 317: 1625–9, CrossRef.




DOI: https://doi.org/10.18585/inabj.v12i2.1045

Indexed by:

                 

                  

               

     

 

The Prodia Education and Research Institute