Advertisement

Biochemical investigation of association of arsenic exposure with risk factors of diabetes mellitus in Pakistani population and its validation in animal model

  • Kanwal Rehman
  • Fiza Fatima
  • Muhammad Sajid Hamid AkashEmail author
Article
  • 122 Downloads

Abstract

Arsenic is one of the naturally occurring heavy metal that has been reported to cause damaging effects on different body organs. This study was aimed to determine the arsenic level in different water sources and investigate the effect of arsenic exposure on risk factors of diabetes mellitus (DM) in human participants and experimental animals. We recruited 150 participants to investigate the arsenic exposure in their urine and from drinking water. We found that males contained significantly higher (P < 0.001) concentrations of urinary arsenic as compared with that of their female counterparts. Similarly, urinary arsenic concentration was high and showed significant association in the age of ≥ 60 years (P < 0.05), illiterate (P < 0.001), smokers (P < 0.0001), and diabetic (P < 0.0001) participants. Moreover, urinary arsenic exposure was also associated with higher levels of fasting (P < 0.001) and random blood glucose (P < 0.001), HbA1c (P < 0.001), AST, ALT, MDA, IL-6, CRP, blood urea nitrogen, and creatinine in arsenic-exposed diabetics as compared with that of unexposed diabetics. Further, we also exposed the white albino rats with arsenic in drinking water for 30 days and their blood glucose was measured at 15th and 30th days of treatment that was significantly higher (P < 0.001) in arsenic-exposed animals as compared with that of unexposed animals. Similarly, arsenic-exposed animals failed to tolerate exogenously administered glucose (P < 0.001) as compared with that of unexposed animals. Likewise, insulin and glutathione concentrations were also significantly decreased (P < 0.001) in arsenic-exposed animals as compared with that of unexposed animals. The alterations in normal values of glucose, insulin, and glutathione exhibited the damaging effects of arsenic exposure in experimental rats. This study showed that arsenic exposed to human beings and animals through drinking water resulted in the disruption of pancreatic β-cell functioning that provoked the risk factor for development of DM. This study also suggested that long-term arsenic exposure induces hyperglycemia, inflammation, and oxidative stress that may lead to the onset of development of DM.

Keywords

Arsenic exposure Diabetes mellitus Arsenic in drinking water Urinary arsenic 

Notes

Funding information

This study was financially supported by the Higher Education Commission (HEC) of Pakistan for (21-667/SRGP/R&D/HEC/2016 and 8365/Punjab/NRPU/R&D/HEC/2017).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Aamir, A. H., Ul-Haq, Z., Mahar, S. A., Qureshi, F. M., Ahmad, I., Jawa, A., Sheikh, A., Raza, A., Fazid, S., & Jadoon, Z. (2019). Diabetes Prevalence Survey of Pakistan (DPS-PAK): prevalence of type 2 diabetes mellitus and prediabetes using HbA1c: a population-based survey from Pakistan. BMJ Open, 9, e025300.CrossRefGoogle Scholar
  2. Afridi, H. I., Kazi, T. G., Kazi, N., Jamali, M. K., Arain, M. B., Jalbani, N., Baig, J. A., & Sarfraz, R. A. (2008). Evaluation of status of toxic metals in biological samples of diabetes mellitus patients. Diabetes Research and Clinical Practice, 80, 280–288.CrossRefGoogle Scholar
  3. Akash, M. S. H., Rehman, K., & Chen, S. (2013). Role of inflammatory mechanisms in pathogenesis of type 2 diabetes mellitus. Journal of Cellular Biochemistry, 114, 525–531.CrossRefGoogle Scholar
  4. Association AD. (2014). Diagnosis and classification of diabetes mellitus. Diabetes Care, 37, S81–S90.CrossRefGoogle Scholar
  5. Atsdr, U. (2007). Toxicological profile for arsenic. Agency for Toxic Substances and Disease Registry. Atlanta, GA: Division of Toxicology.Google Scholar
  6. Bhardwaj, P., Jain, K., & Dhawan, D. K. (2018). Lithium treatment aggregates the adverse effects on erythrocytes subjected to arsenic exposure. Biological Trace Element Research, 184, 206–213.CrossRefGoogle Scholar
  7. Briggs, D. (2003). Environmental pollution and the global burden of disease. British Medical Bulletin, 68, 1–24.CrossRefGoogle Scholar
  8. Campbell, R. K. (2009). Type 2 diabetes: where we are today: an overview of disease burden, current treatments, and treatment strategies. Journal of the American Pharmacists Association, 49, S3–S9.CrossRefGoogle Scholar
  9. Castriota, F., Acevedo, J., Ferreccio, C., Smith, A. H., Liaw, J., Smith, M. T., & Steinmaus, C. (2018). Obesity and increased susceptibility to arsenic-related type 2 diabetes in Northern Chile. Environmental Research, 167, 248–254.CrossRefGoogle Scholar
  10. Chen, C.-J., Hsueh, Y.-M., Lai, M.-S., Shyu, M.-P., Chen, S.-Y., Wu, M.-M., Kuo, T.-L., & Tai, T.-Y. (1995). Increased prevalence of hypertension and long-term arsenic exposure. Hypertension, 25, 53–60.CrossRefGoogle Scholar
  11. Chen, Y., Ahsan, H., Slavkovich, V., Peltier, G. L., Gluskin, R. T., Parvez, F., Liu, X., & Graziano, J. H. (2010). No association between arsenic exposure from drinking water and diabetes mellitus: a cross-sectional study in Bangladesh. Environmental Health Perspectives, 118, 1299–1305.CrossRefGoogle Scholar
  12. Chen, Y., Graziano, J. H., Parvez, F., Liu, M., Slavkovich, V., Kalra, T., Argos, M., Islam, T., Ahmed, A., & Rakibuz-Zaman, M. (2011). Arsenic exposure from drinking water and mortality from cardiovascular disease in Bangladesh: prospective cohort study. BMJ, 342, d2431.CrossRefGoogle Scholar
  13. Chen, Y., Wu, F., Liu, M., Parvez, F., Slavkovich, V., Eunus, M., Ahmed, A., Argos, M., Islam, T., & Rakibuz-Zaman, M. (2013). A prospective study of arsenic exposure, arsenic methylation capacity, and risk of cardiovascular disease in Bangladesh. Environmental Health Perspectives, 121, 832–838.CrossRefGoogle Scholar
  14. Douillet, C., Currier, J., Saunders, J., Bodnar, W. M., Matoušek, T. A., & Styblo, M. (2013). Methylated trivalent arsenicals are potent inhibitors of glucose stimulated insulin secretion by murine pancreatic islets. Toxicology and Applied Pharmacology, 267, 11–15.CrossRefGoogle Scholar
  15. Dover, E., Beck, R., Huang, M., Douillet, C., Wang, Z., Klett, E., & Stýblo, M. (2018). Arsenite and methylarsonite inhibit mitochondrial metabolism and glucose-stimulated insulin secretion in INS-1 832/13 β cells. Archives of Toxicology, 92, 693–704.CrossRefGoogle Scholar
  16. Frediani, J. K., Naioti, E. A., Vos, M. B., Figueroa, J., Marsit, C. J., & Welsh, J. A. (2018). Arsenic exposure and risk of nonalcoholic fatty liver disease (NAFLD) among US adolescents and adults: an association modified by race/ethnicity, NHANES 2005–2014. Environmental Health, 17, 6.CrossRefGoogle Scholar
  17. Gribble, M. O., Howard, B. V., Umans, J. G., Shara, N. M., Francesconi, K. A., Goessler, W., Crainiceanu, C. M., Silbergeld, E. K., Guallar, E., & Navas-Acien, A. (2012). Arsenic exposure, diabetes prevalence, and diabetes control in the Strong Heart Study. American Journal of Epidemiology, 176, 865–874.CrossRefGoogle Scholar
  18. Hong, F., Jin, T., & Zhang, A. (2004). Risk assessment on renal dysfunction caused by co-exposure to arsenic and cadmium using benchmark dose calculation in a Chinese population. Biometals, 17, 573–580.CrossRefGoogle Scholar
  19. Houston, M. C. (2011). Role of mercury toxicity in hypertension, cardiovascular disease, and stroke. The Journal of Clinical Hypertension, 13, 621–627.CrossRefGoogle Scholar
  20. Hsu, L.-I., Hsieh, F.-I., Wang, Y.-H., Lai, T.-S., Wu, M.-M., Chen, C.-J., Chiou, H.-Y., & Hsu, K.-H. (2017). Arsenic exposure from drinking water and the incidence of CKD in low to moderate exposed areas of Taiwan: a 14-year prospective study. American Journal of Kidney Diseases, 70, 787–797.CrossRefGoogle Scholar
  21. Huang, C.-F., Yang, C.-Y., Chan, D.-C., Wang, C.-C., Huang, K.-H., Wu, C.-C., Tsai, K.-S., Yang, R.-S., & Liu, S.-H. (2015). Arsenic exposure and glucose intolerance/insulin resistance in estrogen-deficient female mice. Environmental Health Perspectives, 123, 1138–1144.CrossRefGoogle Scholar
  22. IARC A. (2012). Review of human carcinogens, part C: arsenic, metals, fibres, and dusts. IARC Monographs, Lyon, France, 100, 196–211.Google Scholar
  23. Idrees, M., & Batool, S. (2018). Environmental risk assessment of chronic arsenic in drinking water and prevalence of type 2 diabetes mellitus in Pakistan. Environmental Technology, 1–18.Google Scholar
  24. Izquierdo-Vega, J. A., Soto, C. A., Sanchez-Peña, L. C., De Vizcaya-Ruiz, A., & Del Razo, L. M. (2006). Diabetogenic effects and pancreatic oxidative damage in rats subchronically exposed to arsenite. Toxicology Letters, 160, 135–142.CrossRefGoogle Scholar
  25. James, K. A., Marshall, J. A., Hokanson, J. E., Meliker, J. R., Zerbe, G. O., & Byers, T. E. (2013). A case-cohort study examining lifetime exposure to inorganic arsenic in drinking water and diabetes mellitus. Environmental Research, 123, 33–38.CrossRefGoogle Scholar
  26. Jomova, K., Jenisova, Z., Feszterova, M., Baros, S., Liska, J., Hudecova, D., Rhodes, C., & Valko, M. (2011). Arsenic: toxicity, oxidative stress and human disease. Journal of Applied Toxicology, 31, 95–107.Google Scholar
  27. Kim, N. H., Mason, C. C., Nelson, R. G., Afton, S. E., Essader, A. S., Medlin, J. E., Levine, K. E., Hoppin, J. A., Lin, C., & Knowler, W. C. (2013). Arsenic exposure and incidence of type 2 diabetes in Southwestern American Indians. American Journal of Epidemiology, 177, 962–969.CrossRefGoogle Scholar
  28. Liu, S., Guo, X., Wu, B., Yu, H., Zhang, X., & Li, M. (2014). Arsenic induces diabetic effects through beta-cell dysfunction and increased gluconeogenesis in mice. Scientific Reports, 4, 6894.CrossRefGoogle Scholar
  29. Lobo, V., Patil, A., Phatak, A., & Chandra, N. (2010). Free radicals, antioxidants and functional foods: Impact on human health. Pharmacognosy Reviews, 4, 118.CrossRefGoogle Scholar
  30. Longnecker, M. P., & Daniels, J. L. (2001). Environmental contaminants as etiologic factors for diabetes. Environmental Health Perspectives, 109, 871.Google Scholar
  31. Maiti, S., & Chatterjee, A. K. (2000). Differential response of cellular antioxidant mechanism of liver and kidney to arsenic exposure and its relation to dietary protein deficiency. Environmental Toxicology and Pharmacology, 8, 227–235.CrossRefGoogle Scholar
  32. Maiti, S., & Chatterjee, A. K. (2001). Effects on levels of glutathione and some related enzymes in tissues after an acute arsenic exposure in rats and their relationship to dietary protein deficiency. Archives of Toxicology, 75, 531–537.CrossRefGoogle Scholar
  33. Maull, E. A., Ahsan, H., Edwards, J., Longnecker, M. P., Navas-Acien, A., Pi, J., Silbergeld, E. K., Styblo, M., Tseng, C.-H., & Thayer, K. A. (2012). Evaluation of the association between arsenic and diabetes: a National Toxicology Program workshop review. Environmental Health Perspectives, 120, 1658–1670.CrossRefGoogle Scholar
  34. Milton, A. H., Smith, W., Rahman, B., Hasan, Z., Kulsum, U., Dear, K., Rakibuddin, M., & Ali, A. (2005). Chronic arsenic exposure and adverse pregnancy outcomes in Bangladesh. Epidemiology, 16, 82–86.CrossRefGoogle Scholar
  35. Navas-Acien, A., Silbergeld, E. K., Streeter, R. A., Clark, J. M., Burke, T. A., & Guallar, E. (2006). Arsenic exposure and type 2 diabetes: a systematic review of the experimental and epidemiologic evidence. Environmental Health Perspectives, 114, 641–648.CrossRefGoogle Scholar
  36. Navas-Acien, A., Silbergeld, E. K., Pastor-Barriuso, R., & Guallar, E. (2008). Arsenic exposure and prevalence of type 2 diabetes in US adults. JAMA, 300, 814–822.CrossRefGoogle Scholar
  37. Nesha, M., Islam, M., Ferdous, N., Nazrul, F., Rasker, J. (2018). Chronic arsenic exposure through drinking water and risk of type 2 diabetes mellitus: a study from Bangladesh. J Family Med Prim Care Open Acc: JFOA-113.Google Scholar
  38. Nordstrom, D. K. (2002). Worldwide occurrences of arsenic in ground watereditor^editors: American Association for the Advancement of Science.Google Scholar
  39. Orloff, K., Mistry, K., & Metcalf, S. (2009). Biomonitoring for environmental exposures to arsenic. Journal of Toxicology and Environmental Health, Part B, 12, 509–524.CrossRefGoogle Scholar
  40. Paul, D. S., Walton, F. S., Saunders, R. J., & Stýblo, M. (2011). Characterization of the impaired glucose homeostasis produced in C57BL/6 mice by chronic exposure to arsenic and high-fat diet. Environmental Health Perspectives, 119, 1104–1109.CrossRefGoogle Scholar
  41. Ravenscroft, P. (2007). Predicting the global distribution of natural arsenic contamination of groundwatereditor^editors. Symposium on arsenic: the geography of a global problem. London: Royal Geographical Society.Google Scholar
  42. Rehman, K., & Akash, M. S. H. (2016). Mechanisms of inflammatory responses and development of insulin resistance: how are they interlinked? Journal of Biomedical Science, 23, 87.CrossRefGoogle Scholar
  43. Rehman, K., & Akash, M. S. H. (2017). Mechanism of generation of oxidative stress and pathophysiology of type 2 diabetes mellitus: how are they interlinked? Journal of Cellular Biochemistry, 118, 3577–3585.CrossRefGoogle Scholar
  44. Rezaei, M., Khodayar, M. J., Seydi, E., Soheila, A., & Parsi, I. K. (2017). Acute, but not chronic, exposure to arsenic provokes glucose intolerance in rats: possible roles for oxidative stress and the adrenergic pathway. Canadian Journal of Diabetes, 41, 273–280.CrossRefGoogle Scholar
  45. Salazard, B., Bellon, L., Jean, S., Maraninchi, M., El-Yazidi, C., Orsiere, T., Margotat, A., Botta, A., & Bergé-Lefranc, J.-L. (2004). Low-level arsenite activates the transcription of genes involved in adipose differentiation. Cell Biology and Toxicology, 20, 375–385.CrossRefGoogle Scholar
  46. Santra, A., Maiti, A., Das, S., Lahiri, S., Charkaborty, S. K., Guha Mazumder, D. N., & Guha Mazumder, D. (2000). Hepatic damage caused by chronic arsenic toxicity in experimental animals. Journal of Toxicology. Clinical Toxicology, 38, 395–405.CrossRefGoogle Scholar
  47. Sasaki, A., Oshima, Y., & Fujimura, A. (2007). An approach to elucidate potential mechanism of renal toxicity of arsenic trioxide. Experimental Hematology, 35, 252–262.CrossRefGoogle Scholar
  48. Shafik, N. M., & El Batsh, M. M. (2016). Protective effects of combined selenium and Punica granatum treatment on some inflammatory and oxidative stress markers in arsenic-induced hepatotoxicity in rats. Biological Trace Element Research, 169, 121–128.CrossRefGoogle Scholar
  49. Singh, M. K., Yadav, S. S., Yadav, R. S., Chauhan, A., Katiyar, D., & Khattri, S. (2015). Protective effect of Emblica-officinalis in arsenic induced biochemical alteration and inflammation in mice. Springerplus, 4, 438.CrossRefGoogle Scholar
  50. Tseng, C.-H., Tai, T.-Y., Chong, C.-K., Tseng, C.-P., Lai, M.-S., Lin, B. J., Chiou, H.-Y., Hsueh, Y.-M., Hsu, K.-H., & Chen, C.-J. (2000). Long-term arsenic exposure and incidence of non-insulin-dependent diabetes mellitus: a cohort study in arseniasis-hyperendemic villages in Taiwan. Environmental Health Perspectives, 108, 847–851.CrossRefGoogle Scholar
  51. Valko, M., Morris, H., & Cronin, M. (2005). Metals, toxicity and oxidative stress. Current Medicinal Chemistry, 12, 1161–1208.CrossRefGoogle Scholar
  52. von Ehrenstein, O. S., Poddar, S., Yuan, Y., Mazumder, D. G., Eskenazi, B., Basu, A., Hira-Smith, M., Ghosh, N., Lahiri, S., & Haque, R. (2007). Children’s intellectual function in relation to arsenic exposure. Epidemiology, 18, 44–51.CrossRefGoogle Scholar
  53. Wang, W., Xie, Z., Lin, Y., & Zhang, D. (2014a). Association of inorganic arsenic exposure with type 2 diabetes mellitus: a meta-analysis. Journal of Epidemiology and Community Health, 68, 176–184.CrossRefGoogle Scholar
  54. Wang, X., Zhao, H., Shao, Y., Wang, P., Wei, Y., Zhang, W., Jiang, J., Chen, Y., & Zhang, Z. (2014b). Nephroprotective effect of astaxanthin against trivalent inorganic arsenic-induced renal injury in wistar rats. Nutrition Research and Practice, 8, 46–53.CrossRefGoogle Scholar
  55. Wasserman, G. A., Liu, X., Parvez, F., Ahsan, H., Factor-Litvak, P., van Geen, A., Slavkovich, V., Lolacono, N. J., Cheng, Z., & Hussain, I. (2004). Water arsenic exposure and children’s intellectual function in Araihazar, Bangladesh. Environmental Health Perspectives, 112, 1329–1333.CrossRefGoogle Scholar
  56. Xia, X., Liang, C., Sheng, J., Yan, S., Huang, K., Li, Z., Pan, W., Tao, R., Hao, J., Zhu, B., Tong, S., & Tao, F. (2018). Association between serum arsenic levels and gestational diabetes mellitus: a population-based birth cohort study. Environmental Pollution, 235, 850–856.CrossRefGoogle Scholar
  57. Yuan, Y., Xiao, Y., Yu, Y., Liu, Y., Feng, W., Qiu, G., Wang, H., Liu, B., Wang, J., & Zhou, L. (2018). Associations of multiple plasma metals with incident type 2 diabetes in Chinese adults: the Dongfeng-Tongji Cohort. Environmental Pollution, 237, 917–925.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Institute of Pharmacy, Physiology and PharmacologyUniversity of AgricultureFaisalabadPakistan
  2. 2.Department of Pharmaceutical ChemistryGovernment College UniversityFaisalabadPakistan

Personalised recommendations