Vitamin D3 Reduction in Individuals Exposed to Sulfur Mustard

Document Type : Original Article

Authors

1 Department of Immunology, Immunoregulation Research Center, Shahed University, Tehran, Iran.

2 Department of Biochemistry, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran. 

Abstract

Background: Inflammatory responses in individuals exposed to sulfur mustard occur in some organs such as lung, skin and eyes. These organs manifest overreaction in cellular and humoral immune responses. Over a long period, the immune responses often continues toward chronic inflammatory processes with some interventions. Obviously some elements have been deregulated. Therefore, this study evaluated Vitamin D3 levels as a modulatory agent that could first regulate inflammatory interactions, then switch to suppress inflammatory mechanisms. Several studies showed that Vitamin D3 plays an undeniable role in suppressing inflammatory responses. In addition, some studies showed that calcium and phosphorus could play some role in inflammatory responses, too. Also, levels of serum calcium and phosphorus are associated with serum Vitamin D3 level, because it promotes absorption and reabsorption of calcium and phosphorus in intestine and kidney.
Materials and Methods: Levels of vitamin D3, calcium and phosphorus were measured by ELISA and spectrophotometric method, respectively. 114 exposed individuals as case group and 79 unexposed as control group were evaluated.
Results: The results showed that the level of serum Vitamin D3 is low in individuals exposed to sulfur mustard (PConclusion: According to our findings, chronic inflammation has correlation with status of serum Vitamin D3 deficiency in individuals exposed to sulfur mustard.

Keywords


Ghotbi L, Hassan Z. The immunostatus of natural killer cells in people exposed to sulfur mustard. International Immunopharmacology. 2002; 2(7):981-5. [DOI:10.1016/S1567-5769(02)00053-X]
Ghabili K, Agutter PS, Ghanei M, Ansarin K, Panahi Y, Shoja MM. Sulfur mustard toxicity: History, chemistry, pharmacokinetics, and pharmacodynamics. Critical Reviews in Toxicology. 2011; 41(5):384-403. [DOI:10.3109/10408444.2010.541224] [PMID]
Le HQ, Knudsen SJ. Exposure to a First World War blistering agent. Emergency Medicine Journal. 2006; 23(4):296-9. [DOI:10.1136/emj.2005.032540] [PMID] [PMCID]
Borak J, Sidell FR. Agents of chemical warfare: Sulfur mustard. Annals of Emergency Medicine. 1992; 21(3):303-8. [DOI:10.1016/S0196-0644(05)80892-3]
Dacre JC, Goldman M. Toxicology and pharmacology of the chemical warfare agent sulfur mustard. Pharmacological Reviews. 1996; 48(2):289-326. [PMID]
Ghanei M, Vosoghi AA. An epidemiologic study to screen for chronic myelocytic leukemia in war victims exposed to mustard gas. Environmental Health Perspectives. 2002; 110(5):519-21. [DOI:10.1289/ehp.02110519] [PMID] [PMCID]
Bobb AJ, Arfsten DP, Jederberg WW. N-acetyl-L-Cysteine as prophylaxis against sulfur mustard. Military Medicine. 2005; 170(1):52-6. [DOI:10.7205/MILMED.170.1.52] [PMID]
Balali-Mood M, Hefazi M. Comparison of early and late toxic effects of sulfur mustard in Iranian veterans. Basic & Clinical Pharmacology & Toxicology. 2006; 99(4):273-82. [DOI:10.1111/j.1742-7843.2006.pto_429.x] [PMID]
Javadi MA, Yazdani S, Sajjadi H, Jadidi K, Karimian F, Einollahi B, et al. Chronic and delayed-onset mustard gas keratitis: Report of 48 patients and review of literature. Ophthalmology. 2005; 112(4):617-25. [DOI:10.1016/j.ophtha.2004.09.027] [PMID]
Khateri S, Ghanei M, Keshavarz S, Soroush M, Haines D. Incidence of lung, eye, and skin lesions as late complications in 34,000 Iranians with wartime exposure to mustard agent. Journal of Occupational and Environmental Medicine / American College of Occupational and Environmental Medicine. 2003; 45(11):1136-43. [DOI:10.1097/01.jom.0000094993.20914.d1] [PMID]
Ishida H, Ray R, Ray P. Sulfur mustard downregulates iNOS expression to inhibit wound healing in a human keratinocyte model. Journal of Dermatological Science. 2008; 49(3):207-16. [DOI:10.1016/j.jdermsci.2007.09.002] [PMID]
Ghazanfari T, Kariminia A, Yaraee R, Faghihzadeh S, Ardestani SK, Ebtekar M, et al. Long term impact of sulfur mustard exposure on peripheral blood mononuclear subpopulations--Sardasht-Iran Cohort Study (SICS). International Immunopharmacology. 2013; 17(3):931-5. [DOI:10.1016/j.intimp.2012.12.023] [PMID]
Moin A, Khamesipour A, Hassan ZM, Ebtekar M, Davoudi SM, Vaez-Mahdavi MR, et al. Pro-inflammatory cytokines among individuals with skin findings long-term after sulfur mustard exposure: Sardasht-Iran Cohort Study. International Immunopharmacology. 2013; 17(3):986-90. [DOI:10.1016/j.intimp.2012.12.022] [PMID]
Barnes PJ. Role of HDAC2 in the pathophysiology of COPD. Annual Review of Physiology. 2009; 71:451-64. [DOI:10.1146/annurev.physiol.010908.163257] [PMID]
Ginanjar E, Sumariyono, Setiati S, Setiyohadi B. Vitamin D and autoimmune disease. Acta Medica Indonesiana. 2007; 39(3):133-41. [PMID]
Aranow C. Vitamin D and the immune system. Journal of Investigative Medicine. 2011; 59(6):881-6. [DOI:10.2310/JIM.0b013e31821b8755] [PMID] [PMCID]
Trochoutsou AI, Kloukina V, Samitas K, Xanthou G. Vitamin-D in the Immune System: Genomic and Non-Genomic Actions. Mini Reviews in Medicinal Chemistry. 2015; 15(11):953-63. [DOI:10.2174/1389557515666150519110830] [PMID]
Gynther P, Toropainen S, Matilainen JM, Seuter S, Carlberg C, Vaisanen S. Mechanism of 1alpha,25-dihydroxyvitamin D(3)-dependent repression of interleukin-12B. Biochimica et biophysica Acta. 2011; 1813(5):810-8. [DOI:10.1016/j.bbamcr.2011.01.037] [PMID]
Ferrari M, Schenk K, Papadopoulou C, Ferrari P, Dalle Carbonare L, Bertoldo F. Serum 25-hydroxy vitamin D and exercise capacity in COPD. Thorax. 2011; 66(6):544-5. [DOI:10.1136/thx.2010.152785] [PMID]
Finklea JD, Grossmann RE, Tangpricha V. Vitamin D and chronic lung disease: A review of molecular mechanisms and clinical studies. Advances in Nutrition. 2011; 2(3):244-53. [DOI:10.3945/an.111.000398] [PMID] [PMCID]
Janssens W, Bouillon R, Claes B, Carremans C, Lehouck A, Buysschaert I, et al. Vitamin D deficiency is highly prevalent in COPD and correlates with variants in the vitamin D-binding gene. Thorax. 2010; 65(3):215-20. [DOI:10.1136/thx.2009.120659] [PMID]
Fiaccadori E, Coffrini E, Fracchia C, Rampulla C, Montagna T, Borghetti A. HYpophosphatemia and phosphorus depletion in respiratory and peripheral muscles of patients with respiratory failure due to copd. Chest. 1994; 105(5):1392-8. [DOI:10.1378/chest.105.5.1392] [PMID]
Zhu Y, Mahon BD, Froicu M, Cantorna MT. Calcium and 1 alpha,25-dihydroxyvitamin D3 target the TNF-alpha pathway to suppress experimental inflammatory bowel disease. European Journal of Immunology. 2005; 35(1):217-24. [DOI:10.1002/eji.200425491] [PMID]
Demay MB. Mechanism of vitamin D receptor action. Annals of the New York Academy of Sciences. 2006; 1068(1):204-13. [DOI:10.1196/annals.1346.026] [PMID]
Omdahl JL, Morris HA, May BK. Hydroxylase enzymes of the vitamin D pathway: expression, function, and regulation. Annual Review of Nutrition. 2002; 22(1):139-66. [DOI:10.1146/annurev.nutr.22.120501.150216] [PMID]
Subramanian K, Bergman P, Henriques-Normark B. Vitamin D promotes pneumococcal killing and modulates inflammatory responses in primary human neutrophils. Journal of Innate Immunity. 2017; 9(4):375-86. [DOI:10.1159/000455969] [PMID]
Davis CD, Milner JA. Nutrigenomics, vitamin D and cancer prevention. Journal of Nutrigenetics and Nutrigenomics. 2011; 4(1):1-11. [DOI:10.1159/000324175] [PMID] [PMCID]
Sheng L, Callen DF, Turner AG. Vitamin D3 signaling and breast cancer: Insights from transgenic mouse models. The Journal of Steroid Biochemistry and Molecular Biology. 2018; 178:348-53. [DOI:10.1016/j.jsbmb.2018.02.006] [PMID]
Persson LJ, Aanerud M, Hiemstra PS, Hardie JA, Bakke PS, Eagan TM. Chronic obstructive pulmonary disease is associated with low levels of vitamin D. PloS One. 2012; 7(6):e38934. [DOI:10.1371/journal.pone.0038934] [PMID] [PMCID]
Barker T, Martins TB, Hill HR, Kjeldsberg CR, Dixon BM, Schneider ED, et al. Circulating pro-inflammatory cytokines are elevated and peak power output correlates with 25-hydroxyvitamin D in vitamin D insufficient adults. European Journal of Applied Physiology. 2013; 113(6):1523-34. [DOI:10.1007/s00421-012-2582-7] [PMID]
An BS, Tavera-Mendoza LE, Dimitrov V, Wang X, Calderon MR, Wang HJ, et al. Stimulation of Sirt1-regulated FoxO protein function by the ligand-bound vitamin D receptor. Molecular and Cellular Biology. 2010; 30(20):4890-900. [DOI:10.1128/MCB.00180-10] [PMID] [PMCID]
Rajendrasozhan S, Yang SR, Kinnula VL, Rahman I. SIRT1, an antiinflammatory and antiaging protein, is decreased in lungs of patients with chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine. 2008; 177(8):861-70. [DOI:10.1164/rccm.200708-1269OC] [PMID] [PMCID]