Clinical and molecular aspects of lead toxicity: An update

Abstract

Lead toxicity is a major public health issue in developed and developing countries. Both acute and chronic lead exposure has the potential to cause many deleterious systematic effects including hypertension, frank anemia, cognitive deficits, infertility, immune imbalances, delayed skeletal and deciduous dental development, vitamin D deficiency, and gastrointestinal effects. The underlying mechanisms for all these systemic effects have not been elucidated completely. However, the most plausible cause is free radical damage. In addition to this, lead being a divalent cation can surrogate for calcium at multiple levels affecting various cell signaling pathways. The molecular basis of lead exposure resulting in various systemic effects is being extensively explored. The reports include single nucleotide polymorphisms, epigenetic modifications in susceptible individuals, and the most recent reports also feature regulatory RNA molecules - miRNAs. However, many genetic targets are identified, but their possible mechanisms are still an area to be explored. Additional studies are needed in different population groups to validate the existing findings, as well as to find newer targets that may help in better understanding the molecular mechanisms contributing to lead toxicity. Furthermore, newer strategies for lead risk assessment becomes necessary as the previously recognized "safe" level of lead is also being found to be associated with negative health outcomes.

The role of iron repletion in adult iron deficiency anemia and other diseases

“…41 Lead toxicity can rarely cause microcytic or normocytic anemia in children through decreased hemoglobin synthesis and hemolysis by generation of reactive oxygen species. 43,44 Lead is known to adversely affect hemoglobin synthesis through inhibition of multiple enzymes involved in porphyrin synthesis and iron incorporation into the porphyrin ring. 44 Both capillary blood testing and venous sampling can accurately detect elevated blood lead levels in children.…”

“…43,44 Lead is known to adversely affect hemoglobin synthesis through inhibition of multiple enzymes involved in porphyrin synthesis and iron incorporation into the porphyrin ring. 44 Both capillary blood testing and venous sampling can accurately detect elevated blood lead levels in children. 45 Management involves elimination of the lead source with chelation therapy if blood lead concentrations exceed 45 µg/dL.…”

Immunomodulation by Coriandrum sativum seeds (Coriander) and its ameliorative effect on lead‐induced immunotoxicity in Nile tilapia ( Oreochromis niloticus L.)

“…The exposure of Procambarus clarkii to 100 mg/L of lead for 96 hr was enough to induce changes in the ultrastructure of the gill filaments epithelial cells and the cuticle (Rubio, Tineo, Torreblanca, Del Ramo, & Mayans, 1991). Pb is considered to be not only a common non-degradable toxic contaminant in freshwaters (Khallaf, Authman, & Alne-na-ei, 2018;Kim & Kang, 2017;Osman & Kloas, 2010), but also a serious health hazard (Mitra, Sharma, Purohit, & Sharma, 2017). Presence of Pb in the water bodies is often related to mining, coal burning, traffic, industrial processing and other anthropogenic activities (Hadji, Urien, Uher, Fechner, & Lebrun, 2016).…”

“…Presence of Pb in the water bodies is often related to mining, coal burning, traffic, industrial processing and other anthropogenic activities (Hadji, Urien, Uher, Fechner, & Lebrun, 2016). The non-biodegradable nature of Pb is the main reason for its persistence in the environment (Mitra et al, 2017), and the simultaneous exposure to waterborne Pb is likely to occur (Alsop, Ng, Chowdhury, & Wood, 2016). The consequences of lead exposure, in human and aquatic animals, have been demonstrated in a number of research papers, reviews and books, whom all are stated that lead exposure is associated with various adverse effects in many organ systems (Authman et al, 2015;Mishra, 2009;Mishra, Rani, Yadav, & Naik, 2010;Mitra et al, 2017;Sfakianakis et al, 2015).…”

“…The non-biodegradable nature of Pb is the main reason for its persistence in the environment (Mitra et al, 2017), and the simultaneous exposure to waterborne Pb is likely to occur (Alsop, Ng, Chowdhury, & Wood, 2016). The consequences of lead exposure, in human and aquatic animals, have been demonstrated in a number of research papers, reviews and books, whom all are stated that lead exposure is associated with various adverse effects in many organ systems (Authman et al, 2015;Mishra, 2009;Mishra, Rani, Yadav, & Naik, 2010;Mitra et al, 2017;Sfakianakis et al, 2015). The immune system has been recognized to be one of the sensitive targets of lead toxicity, not only in human (Mishra, 2009;Mitra et al, 2017) but also in fish (Paul et al, 2014;Shah & Altindağ, 2005).…”