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4 Circulating miRNAs as Biomarkers of Toxic Heavy Metal Exposure

       Alexandra N. Nail, Ana P. Ferragut Cardoso, Mayukh Banerjee, and J. Christopher States

       Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY

      Metals and the Focus of This Chapter

      Metals are defined as elements that readily form cations and are composed of a lattice of positive ions surrounded by a cloud of delocalized electrons. Heavy metals have played an important role in human civilization for thousands of years. Commonly defined by their specific density (greater than 5.0 g/cm³), heavy metals occur naturally in the environment. Five heavy metals, namely arsenic (which is classified as a metalloid but is often grouped within heavy metals), lead, mercury, cadmium, and chromium, are of considerable public health importance because of their high degree of toxicity (Jarup 2003). In fact arsenic, lead, mercury, and cadmium are ranked within the top seven substances in the Agency for Toxic Substances and Disease Registry’s Substance Priority List, which considers a combination of frequency, toxicity, and potential for human exposure when classifying substances of concern (ATSDR 2019). While metals often occur naturally in the environment, anthropogenic activities such as mining, smelting, industrial production, and agriculture can lead to their increased mobilization and can alter their chemical form, thereby also altering their toxicity. Human activities thus contribute to environmental and occupational exposure to arsenic, lead, mercury, cadmium, and chromium. Exposure to these metals can cause a myriad of health problems such as multiple organ damage, cellular damage, cardiovascular and metabolic diseases, and cancer (Rehman et al. 2018).

      In general, concentrations of metals in biological samples are used as biomarkers for assessing the level of concern with metal intoxication. As technologies continue to improve in molecular toxicology, biomarker possibilities have expanded. This chapter discusses circulating

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