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Low levels of lead and glutathione markers of redox status in human blood

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Abstract

Exposure to lead (Pb) is implicated in a plethora of health threats in both adults and children. Increased exposure levels are associated with oxidative stress in the blood of workers exposed at occupational levels. However, it is not known whether lower Pb exposure levels are related to a shift toward a more oxidized state. To assess the association between blood lead level (BLL) and glutathione (GSH) redox biomarkers in a population of healthy adults, BLL and four GSH markers (GSH, GSSG, GSH/GSSG ratio and redox potential E h ) were measured in the blood of a cross-sectional cohort of 282 avid seafood-eating healthy adults living on Long Island (NY). Additionally, blood levels of two other metals known to affect GSH redox status, selenium (Se) and mercury (Hg), and omega-3 index were tested for effect modification. Regression models were further adjusted for demographic and smoking status. Increasing exposure to Pb, measured in blood, was not associated with GSSG, but was associated with lower levels of GSH/GSSG ratio and more positive GSH redox potential E h , driven by its association with GSH. No effect modification was observed in analyses stratified by Hg, Se, omega-3 index, sex, age, or smoking. Blood Pb is associated with lower levels of GSH and the GSH/GSSG ratio in this cross-sectional study of healthy adults.

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References

  • Agency for Toxic Substances and Disease Registry (ATSDR). (2007). Toxicological profile for lead. Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service.

    Google Scholar 

  • Agency for Toxic Substances and Disease Registry (ATSDR). (2010). Case Studies in Environmental Medicine: Lead Toxicity. http://www.atsdr.cdc.gov/csem/lead/docs/lead.pdf.

  • Ahamed, M., & Siddiqui, M. K. J. (2007). Environmental lead toxicity and nutritional factors. Clinical Nutrition, 26(4), 400–408. doi:10.1016/j.clnu.2007.03.010.

    Article  CAS  Google Scholar 

  • Ahamed, M., Verma, S., Kumar, A., & Siddiqui, M. K. (2005). Environmental exposure to lead and its correlation with biochemical indices in children. Science of the Total Environment, 346(1–3), 48–55. doi:10.1016/j.scitotenv.2004.12.019.

    Article  CAS  Google Scholar 

  • Bellinger, D. C. (2008). Late neurodevelopmental effects of early exposures to chemical contaminants: Reducing uncertainty in epidemiological studies. Basic & Clinical Pharmacology & Toxicology, 102(2), 237–244. doi:10.1111/j.1742-7843.2007.00164.x.

    Article  CAS  Google Scholar 

  • Canfield, R. L., Henderson, C. R., Jr., Cory-Slechta, D. A., Cox, C., Jusko, T. A., & Lanphear, B. P. (2003). Intellectual impairment in children with blood lead concentrations below 10 microg per deciliter. New England Journal of Medicine, 348(16), 1517–1526. doi:10.1056/NEJMoa022848.

    Article  CAS  Google Scholar 

  • Centers for Disease Control and Prevention (CDC). (2014). Blood Lead Levels in Children. http://www.cdc.gov/nceh/lead/acclpp/lead_levels_in_children_fact_sheet.pdf.

  • Chen, A., Dietrich, K. N., Ware, J. H., Radcliffe, J., & Rogan, W. J. (2005). IQ and blood lead from 2 to 7 years of age: Are the effects in older children the residual of high blood lead concentrations in 2-year-olds? Environmental Health Perspectives, 113(5), 597–601.

    Article  CAS  Google Scholar 

  • Chiodo, L. M., Jacobson, S. W., & Jacobson, J. L. (2004). Neurodevelopmental effects of postnatal lead exposure at very low levels. Neurotoxicology and Teratology, 26(3), 359–371. doi:10.1016/j.ntt.2004.01.010.

    Article  CAS  Google Scholar 

  • Circu, M. L., & Aw, T. Y. (2010). Reactive oxygen species, cellular redox systems, and apoptosis. Free Radical Biology and Medicine, 48(6), 749–762. doi:10.1016/j.freeradbiomed.2009.12.022.

    Article  CAS  Google Scholar 

  • Dalle-Donne, I., Rossi, R., Colombo, R., Giustarini, D., & Milzani, A. (2006). Biomarkers of oxidative damage in human disease. Clinical Chemistry, 52(4), 601–623. doi:10.1373/clinchem.2005.061408.

    Article  CAS  Google Scholar 

  • Devi, S. S., Biswas, A. R., Biswas, R. A., Vinayagamoorthy, N., Krishnamurthi, K., Shinde, V. M., et al. (2007). Heavy metal status and oxidative stress in diesel engine tuning workers of central Indian population. Journal of Occupational and Environmental Medicine, 49(11), 1228–1234. doi:10.1097/JOM.0b013e3181565d29.

    Article  CAS  Google Scholar 

  • Enns, G. M., Moore, T., Le, A., Atkuri, K., Shah, M. K., Cusmano-Ozog, K., et al. (2014). Degree of glutathione deficiency and redox imbalance depend on subtype of mitochondrial disease and clinical status. PLoS ONE, 9(6), e100001. doi:10.1371/journal.pone.0100001.

    Article  CAS  Google Scholar 

  • Ercal, N., Gurer-Orhan, H., & Aykin-Burns, N. (2001). Toxic metals and oxidative stress part I: Mechanisms involved in metal-induced oxidative damage. Current Topics in Medicinal Chemistry, 1(6), 529–539.

    Article  CAS  Google Scholar 

  • Ergurhan-Ilhan, I., Cadir, B., Koyuncu-Arslan, M., Arslan, C., Gultepe, F. M., & Ozkan, G. (2008). Level of oxidative stress and damage in erythrocytes in apprentices indirectly exposed to lead. Pediatrics International, 50(1), 45–50. doi:10.1111/j.1442-200X.2007.02442.x.

    Article  CAS  Google Scholar 

  • Flora, G., Gupta, D., & Tiwari, A. (2012). Toxicity of lead: A review with recent updates. Interdiscip Toxicol, 5(2), 47–58. doi:10.2478/v10102-012-0009-2.

    Article  CAS  Google Scholar 

  • Garcon, G., Leleu, B., Zerimech, F., Marez, T., Haguenoer, J. M., Furon, D., et al. (2004). Biologic markers of oxidative stress and nephrotoxicity as studied in biomonitoring of adverse effects of occupational exposure to lead and cadmium. Journal of Occupational and Environmental Medicine, 46(11), 1180–1186.

    Article  CAS  Google Scholar 

  • Gurer, H., & Ercal, N. (2000). Can antioxidants be beneficial in the treatment of lead poisoning? Free Radical Biology and Medicine, 29(10), 927–945.

    Article  CAS  Google Scholar 

  • Gurer-Orhan, H., Sabır, H. U., & Özgüneş, H. (2004). Correlation between clinical indicators of lead poisoning and oxidative stress parameters in controls and lead-exposed workers. Toxicology, 195(2–3), 147–154. doi:10.1016/j.tox.2003.09.009.

    Article  CAS  Google Scholar 

  • Hall, M. N., Niedzwiecki, M., Liu, X., Harper, K. N., Alam, S., Slavkovich, V., et al. (2013). Chronic arsenic exposure and blood glutathione and glutathione disulfide concentrations in bangladeshi adults. Environmental Health Perspectives, 121(9), 1068–1074. doi:10.1289/ehp.1205727.

    Article  CAS  Google Scholar 

  • Hunaiti, A. A., & Soud, M. (2000). Effect of lead concentration on the level of glutathione, glutathione S-transferase, reductase and peroxidase in human blood. Science of the Total Environment, 248(1), 45–50.

    Article  CAS  Google Scholar 

  • Jomova, K., & Valko, M. (2011). Advances in metal-induced oxidative stress and human disease. Toxicology, 283(2–3), 65–87. doi:10.1016/j.tox.2011.03.001.

    Article  CAS  Google Scholar 

  • Jones, D. P. (2001). Redox potential of GSH/GSSG couple: Assay and biological significance. Methods in Enzymology, 348, 93–112.

    Article  Google Scholar 

  • Kanehisa, M., & Goto, S. (2000). KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Research, 28(1), 27–30.

    Article  CAS  Google Scholar 

  • Karimi, R., Fisher, N. S., & Meliker, J. R. (2014a). Mercury-nutrient signatures in seafood and in the blood of avid seafood consumers. Science of the Total Environment, 496, 636–643. doi:10.1016/j.scitotenv.2014.04.049.

    Article  CAS  Google Scholar 

  • Karimi, R., Silbernagel, S., Fisher, N. S., & Meliker, J. R. (2014b). Elevated blood Hg at recommended seafood consumption rates in adult seafood consumers. International Journal of Hygiene and Environmental Health, 217(7), 758–764. doi:10.1016/j.ijheh.2014.03.007.

    Article  CAS  Google Scholar 

  • Karimi, R., Vacchi-Suzzi, C., & Meliker, J. R. (2015). Mercury exposure and a shift toward oxidative stress in avid seafood consumers. Environmental Research, 146, 100–107. doi:10.1016/j.envres.2015.12.023.

    Article  CAS  Google Scholar 

  • Kasperczyk, S., Blaszczyk, I., Dobrakowski, M., Romuk, E., Kapka-Skrzypczak, L., Adamek, M., et al. (2013). Exposure to lead affects male biothiols metabolism. Annals of Agricultural and Environmental Medicine, 20(4), 721–725.

    CAS  Google Scholar 

  • Kasperczyk, S., Kasperczyk, A., Ostalowska, A., Dziwisz, M., & Birkner, E. (2004). Activity of glutathione peroxidase, glutathione reductase, and lipid peroxidation in erythrocytes in workers exposed to lead. Biological Trace Element Research, 102(1–3), 61–72.

    Article  CAS  Google Scholar 

  • Kyoto Encyclopedia of Genes and Genomes Glutathione metabolism - Reference pathway. (2000). http://www.genome.jp/kegg/pathway/map/map00480.html. Accessed 30 March 2017.

  • Lanphear, B. P., Dietrich, K., Auinger, P., & Cox, C. (2000). Cognitive deficits associated with blood lead concentrations < 10 microg/dL in US children and adolescents. Public Health Reports, 115(6), 521–529.

    Article  CAS  Google Scholar 

  • Lee, D. H., Lim, J. S., Song, K., Boo, Y., & Jacobs, D. R., Jr. (2006). Graded associations of blood lead and urinary cadmium concentrations with oxidative-stress-related markers in the U.S. population: Results from the third National Health and Nutrition Examination Survey. Environmental Health Perspectives, 114(3), 350–354.

    Article  CAS  Google Scholar 

  • Liu, M. C., Xu, Y., Chen, Y. M., Li, J., Zhao, F., Zheng, G., et al. (2013). The effect of sodium selenite on lead induced cognitive dysfunction. Neurotoxicology, 36, 82–88. doi:10.1016/j.neuro.2013.03.008.

    Article  CAS  Google Scholar 

  • Malekirad, A. A., Oryan, S., Fani, A., Babapor, V., Hashemi, M., Baeeri, M., et al. (2010). Study on clinical and biochemical toxicity biomarkers in a zinc-lead mine workers. Toxicology and Industrial Health, 26(6), 331–337. doi:10.1177/0748233710365697.

    Article  CAS  Google Scholar 

  • Martinez-Haro, M., Green, A. J., & Mateo, R. (2011). Effects of lead exposure on oxidative stress biomarkers and plasma biochemistry in waterbirds in the field. Environmental Research, 111(4), 530–538. doi:10.1016/j.envres.2011.02.012.

    Article  CAS  Google Scholar 

  • Occupational Safety and Health Administration (OSHA). (2014). Safety and health topics: Lead. https://www.osha.gov/SLTC/lead/. Accessed 4 June 2015.

  • Othman, A. I., & El Missiry, M. A. (1998). Role of selenium against lead toxicity in male rats. Journal of Biochemical and Molecular Toxicology, 12(6), 345–349.

    Article  CAS  Google Scholar 

  • Owen, J. B., & Butterfield, D. A. (2010). Measurement of oxidized/reduced glutathione ratio. In P. Bross & N. Gregersen (Eds.), Protein misfolding and cellular stress in disease and aging: Concepts and protocols (Methods in molecular biology) (Vol. 648, pp. 269–277). Totowa: Humana Press Inc.

    Chapter  Google Scholar 

  • Pande, M., & Flora, S. J. (2002). Lead induced oxidative damage and its response to combined administration of alpha-lipoic acid and succimers in rats. Toxicology, 177(2–3), 187–196.

    Article  CAS  Google Scholar 

  • Patrick, L. (2006). Lead toxicity part II: The role of free radical damage and the use of antioxidants in the pathology and treatment of lead toxicity. Altern Med Rev, 11(2), 114–127.

    Google Scholar 

  • Reddy, C. C., & Massaro, E. J. (1983). Biochemistry of selenium: A brief overview. Fundamental and Applied Toxicology, 3(5), 431–436.

    Article  CAS  Google Scholar 

  • Rossi, R., Milzani, A., Dalle-Donne, I., Giustarini, D., Lusini, L., Colombo, R., et al. (2002). Blood glutathione disulfide: In vivo factor or in vitro artifact? Clinical Chemistry, 48(5), 742–753.

    CAS  Google Scholar 

  • Schafer, F. Q., & Buettner, G. R. (2001). Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radical Biology and Medicine, 30(11), 1191–1212.

    Article  CAS  Google Scholar 

  • Sciskalska, M., Zalewska, M., Grzelak, A., & Milnerowicz, H. (2014). The influence of the occupational exposure to heavy metals and tobacco smoke on the selected oxidative stress markers in smelters. Biological Trace Element Research, 159(1–3), 59–68. doi:10.1007/s12011-014-9984-9.

    Article  CAS  Google Scholar 

  • Sinicropi, M. S., Amantea, D., Caruso, A., & Saturnino, C. (2010). Chemical and biological properties of toxic metals and use of chelating agents for the pharmacological treatment of metal poisoning. Archives of Toxicology, 84(7), 501–520. doi:10.1007/s00204-010-0544-6.

    Article  CAS  Google Scholar 

  • Sugawara, E., Nakamura, K., Miyake, T., Fukumura, A., & Seki, Y. (1991). Lipid peroxidation and concentration of glutathione in erythrocytes from workers exposed to lead. British Journal of Industrial Medicine, 48(4), 239–242.

    CAS  Google Scholar 

  • von Schacky, C., & Harris, W. S. (2007). Cardiovascular risk and the omega-3 index. Journal of Cardiovascular Medicine (Hagerstown), 8(Suppl 1), S46–S49. doi:10.2459/01.jcm.0000289273.87803.87.

    Article  Google Scholar 

  • Yuan, X., & Tang, C. (2001). The accumulation effect of lead on DNA damage in mice blood cells of three generations and the protection of selenium. Journal of Environmental Science and Health Part A Toxic/Hazardous Substances & Environmental Engineering, 36(4), 501–508.

    Article  CAS  Google Scholar 

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Acknowledgements

We wish to thank the participants and research support staff of the Long Island Seafood Study, including the Clinical Research Core at Stony Brook Medical Center, Izolda Mileva, Susan Silbernagel, Karen Warren, Nikita Timofeev, Jia Juan (Tommy) Chu, Rebecca Monastero, Paige de Rosa, and Shivam Kothari. This work was supported by NY SeaGrant# R/SHH-17 and the Gelfond Fund for Mercury Research and Outreach (Stony Brook University, Stony Brook, NY). The study was reviewed and approved by Stony Brook University’s Institutional Review Board for human subjects (IRB# 2010-1179).

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Correspondence to Caterina Vacchi-Suzzi.

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Vacchi-Suzzi, C., Viens, L., Harrington, J.M. et al. Low levels of lead and glutathione markers of redox status in human blood. Environ Geochem Health 40, 1175–1185 (2018). https://doi.org/10.1007/s10653-017-0034-3

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