Abstract
Benzene is a ubiquitous environmental pollutant with various health effects. It is reported that benzene exposure might be associated with insulin resistance in elderly adults. The aim of this study is to investigate the association between urinary benzene metabolite, trans, trans-muconic acid (t,t-ma) and markers of oxidative stress and insulin resistance in children and adolescents. This cross-sectional study was conducted in 2017 among 86 children and adolescents, aged 6–18 years, living in Isfahan, Iran. t,t-ma was measured as urinary benzene metabolite and homeostasis model assessment (HOMA-IR) was determined as an index of insulin resistance. Moreover, malondialdehyde (MDA) and superoxide dismutase (SOD) were assessed as oxidative stress markers. We found significant association between insulin resistance, fasting blood glucose, and fasting blood insulin with t,t-ma (p values = 0.002, 0.03, and 0.001, respectively). Results of this study indicate that benzene metabolite in higher concentrations in comparison with lower concentrations is associated with increased risk of insulin resistance. Moreover, after adjustment for age, sex, and household passive smoking, statistically significant increase were documented in SOD and MDA (4.49- and 3.54-fold, respectively) in intermediate levels of t,t-ma vs. low levels of t,t-ma (p values = 0.01 and 0.034, respectively). To the best of our knowledge, this is the first study in its kind in the pediatric age group. It showed that benzene exposures, even in environmental levels, might be associated with insulin resistance and oxidative stress in children and adolescents. Further longitudinal studies are necessary to assess the clinical impacts of this finding.
Similar content being viewed by others
References
Agodi A, Oliveri Conti G, Barchitta M, Quattrocchi A, Lombardo BM, Montesanto G, Messina G, Fiore M, Ferrante M (2015) Validation of Armadillo officinalis Dumèril, 1816 (Crustacea, Isopoda, Oniscidea) as a bioindicator: in vivo study of air benzene exposure. Ecotoxicol Environ Saf 114:171–178
Andersen ZJ, Raaschou-Nielsen O, Ketzel M, Jensen SS, Hvidberg M, Loft S, Tjonneland A, Overvad K, Sorensen M (2012) Diabetes incidence and long-term exposure to air pollution. Diabetes Care 35:92–98
Bahadar H, Mostafalou S, Abdollahi M (2014) Current understandings and perspectives on non-cancer health effects of benzene: a global concern. Toxicol Appl Pharmacol 276:83–94
Bahadar H, Maqbool F, Mostafalou S, Baeeri M, Rahimifard M, Navaei-Nigjeh M, Abdollahi M (2015) Assessment of benzene induced oxidative impairment in rat isolated pancreatic islets and effect on insulin secretion. Environ Toxicol Pharmacol 39:1161–1169
Barbieri A, Violante FS, Sabatini L, Graziosi F, Mattioli S (2008) Urinary biomarkers and low-level environmental benzene concentration: assessing occupational and general exposure. Chemosphere 74:64–69
Barr DB, Wilder LC, Caudill SP, Gonzalez AJ, Needham LL, Pirkle JL (2005) Urinary creatinine concentrations in the US population: implications for urinary biologic monitoring measurements. Environ Health Perspect 113:192–200
Bayliss D, Jinot J, Sonawane B (2002) Toxicological review of benzene (noncancer effects). US EPA Office of Research and Development, Washington
Brook RD, Jerrett M, Brook JR, Bard RL, Finkelstein MM (2008) The relationship between diabetes mellitus and traffic-related air pollution. J Occup Environ Med 50:32–38. https://doi.org/10.1097/JOM.0b013e31815dba70
Cancer IAfRo (1987) IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans. V. 42: Silica and some silicates
Ceriello A (2003) New insights on oxidative stress and diabetic complications may lead to a “causal” antioxidant therapy. Diabetes Care 26:1589–1596
Choi Y-H, Kim JH, Lee B-E, Hong Y-C (2014) Urinary benzene metabolite and insulin resistance in elderly adults. Sci Total Environ 482:260–268
Draper HH, Hadley M (1990) [43] malondialdehyde determination as index of lipid. Peroxidation. Methods Enzymol 186:421–431. https://doi.org/10.1016/0076-6879(90)86135-I
Eze IC, Schaffner E, Fischer E, Schikowski T, Adam M, Imboden M, Tsai M, Carballo D, von Eckardstein A, Künzli N, Schindler C, Probst-Hensch N (2014) Long-term air pollution exposure and diabetes in a population-based Swiss cohort. Environ Int 70:95–105
French JE, Gatti DM, Morgan DL, Kissling GE, Shockley KR, Knudsen GA, Shepard KG, Price HC, King D, Witt KL, Pedersen LC, Munger SC, Svenson KL, Churchill GA (2015) Diversity outbred mice identify population-based exposure thresholds and genetic factors that influence benzene-induced genotoxicity. Environ Health Perspect 123:237–245
Giacco F, Brownlee M (2010) Oxidative stress and diabetic complications. Circ Res 107:1058–1070
Goldberg MS, Burnett RT, Yale J-F, Valois M-F, Brook JR (2006) Associations between ambient air pollution and daily mortality among persons with diabetes and cardiovascular disease. Environ Res 100:255–267
Harrison D, Griendling KK, Landmesser U, Hornig B, Drexler H (2003) Role of oxidative stress in atherosclerosis. Am J Cardiol 91:7–11
Joo W-A, Sul D, Lee D-Y, Lee E, Kim C-W (2004) Proteomic analysis of plasma proteins of workers exposed to benzene. Mutat Res Genet Toxicol Environ Mutagen 558:35–44
Kelishadi R, Mirghaffari N, Poursafa P, Gidding SS (2009) Lifestyle and environmental factors associated with inflammation, oxidative stress and insulin resistance in children. Atherosclerosis 203:311–319
Khan S, Yusufi A (2009) Effect of benzene on the enzymes of carbohydrate metabolism, brush border membrane (BBM) and oxidative stress in kidney and other rat tissues. Biol Med 1:28–41
Krämer U, Herder C, Sugiri D, Strassburger K, Schikowski T, Ranft U, Rathmann W (2010) Traffic-related air pollution and incident type 2 diabetes: results from the SALIA cohort study. Environ Health Perspect 118:1273–1279
Manini P, de Palma G, Andreoli R, Poli D, Petyx M, Corradi M, Mutti A, Apostoli P (2008) Biological monitoring of low benzene exposure in Italian traffic policemen. Toxicol Lett 181:25–30
Marrubini G, Coccini T, Maestri L, Manzo L (2002) Effect of sorbic acid administration on urinary trans, trans-muconic acid excretion in rats exposed to low levels of benzene. Food Chem Toxicol 40:1799–1806
Matthews D, Hosker J, Rudenski A, Naylor B, Treacher D, Turner R (1985) Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419
Maull EA, Ahsan H, Edwards J, Longnecker MP, Navas-Acien A, Pi J, Silbergeld EK, Styblo M, Tseng CH, Thayer KA, Loomis D (2012) Evaluation of the association between arsenic and diabetes: a National Toxicology Program workshop review. Environ Health Perspect 120:1658–1670. https://doi.org/10.1289/ehp.1104579
O’Neill MS et al (2007) Air pollution and inflammation in type 2 diabetes: a mechanism for susceptibility. Occup Environ Med 64:373–379
Peng Q, Harlow SD, Park SK (2015) Urinary arsenic and insulin resistance in US adolescents. Int J Hyg Environ Health 218:407–413
Poursafa P, Kelishadi R, Moattar F, Rafiee L, Amin MM, Lahijanzadeh A, Javanmard SH (2011) Genetic variation in the association of air pollutants with a biomarker of vascular injury in children and adolescents in Isfahan, Iran. J Res Med Sci 16:733
Qu Q, Melikian AA, Li G, Shore R, Chen L, Cohen B, Yin S, Kagan MR, Li H, Meng M, Jin X, Winnik W, Li Y, Mu R, Li K (2000) Validation of biomarkers in humans exposed to benzene: urine metabolites. Am J Ind Med 37:522–531
Raaschou-Nielsen O et al (2013) Long-term exposure to traffic-related air pollution and diabetes-associated mortality: a cohort study. Diabetologia 56:36–46
Rains JL, Jain SK (2011) Oxidative stress, insulin signaling, and diabetes. Free Radic Biol Med 50:567–575
Rezaee M, Assadi Y, Hosseini M-RM, Aghaee E, Ahmadi F, Berijani S (2006) Determination of organic compounds in water using dispersive liquid–liquid microextraction. J Chromatogr A 1116:1–9
Sankar P, Zachariah B, Vickneshwaran V, Jacob SE, Sridhar M (2015) Amelioration of oxidative stress and insulin resistance by soy isoflavones (from Glycine max) in ovariectomized Wistar rats fed with high fat diet: the molecular mechanisms. Exp Gerontol 63:67–75
Scherer G, Renner T, Meger M (1998) Analysis and evaluation of trans, trans-muconic acid as a biomarker for benzene exposure. J Chromatogr B Biomed Sci Appl 717:179–199
Sun Q, Yue P, Deiuliis JA, Lumeng CN, Kampfrath T, Mikolaj MB, Cai Y, Ostrowski MC, Lu B, Parthasarathy S, Brook RD, Moffatt-Bruce SD, Chen LC, Rajagopalan S (2009) Ambient air pollution exaggerates adipose inflammation and insulin resistance in a mouse model of diet-induced obesity. Circulation 119:538–546. https://doi.org/10.1161/circulationaha.108.799015
Thiering E, Cyrys J, Kratzsch J, Meisinger C, Hoffmann B, Berdel D, von Berg A, Koletzko S, Bauer CP, Heinrich J (2013) Long-term exposure to traffic-related air pollution and insulin resistance in children: results from the GINIplus and LISAplus birth cohorts. Diabetologia 56:1696–1704. https://doi.org/10.1007/s00125-013-2925-x
Tsatsoulis A, Mantzaris MD, Bellou S, Andrikoula M (2013) Insulin resistance: an adaptive mechanism becomes maladaptive in the current environment—an evolutionary perspective. Metabolism 62:622–633
Vinci RM, Canfyn M, De Meulenaer B, De Schaetzen T, Van Overmeire I, De Beer J, Van Loco J (2010) Determination of benzene in different food matrices by distillation and isotope dilution HS-GC/MS. Anal Chim Acta 672:124–129
Weisel CP (2010) Benzene exposure: an overview of monitoring methods and their findings. Chem Biol Interact 184:58–66
West IC (2000) Radicals and oxidative stress in diabetes. Diabet Med 17:171–180
Zimmet P, Alberti K, Shaw J (2001) Global and societal implications of the diabetes epidemic. Nature 414:782–787
Acknowledgments
We thank Engineer Babak Sadeghian (Laboratories Manager, Isfahan DOE) and Engineer Hamid Zohrabi (Head of Isfahan DOE) for providing PM2.5 data.
Funding
This study was funded by Isfahan University of Medical Sciences, Research Project No. 194061.
Author information
Authors and Affiliations
Corresponding author
Additional information
Responsible editor: Philippe Garrigues
Rights and permissions
About this article
Cite this article
Amin, M.M., Rafiei, N., Poursafa, P. et al. Association of benzene exposure with insulin resistance, SOD, and MDA as markers of oxidative stress in children and adolescents. Environ Sci Pollut Res 25, 34046–34052 (2018). https://doi.org/10.1007/s11356-018-3354-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11356-018-3354-7