A pharmacokinetic model of lead absorption and calcium competitive dynamics

Abstract

Lead is a naturally-occurring element. It has been known to man for a long time, and it is one of the longest established poisons. The current consensus is that no level of lead exposure should be deemed “safe”. New evidence regarding the blood levels at which morbidities occur has prompted the CDC to reduce the screening guideline of 10 μg/dl to 2 μg/dl. Measurable cognitive decline (reduced IQ, academic deficits) have been found to occur at levels below 10 μg/dl, especially in children. Knowledge of lead pharmacology allows us to better understand its absorption and metabolization, mechanisms that produce its medical consequences. Based upon an original and very simplified compartmental model of Rabinowitz (1973) with only three major compartments (blood, bone and soft tissue), extensive biophysical models sprouted over the following two decades. However, none of these models have been specifically designed to use new knowledge of lead molecular dynamics to understand its deleterious effects on the brain. We build and analyze a compartmental model of lead pharmacokinetics, focused specifically on addressing neurotoxicity. We use traditional phase space methods, parameter sensitivity analysis and bifurcation theory to study the transitions in the system’s behavior in response to various physiological parameters. We conclude that modeling the complex interaction of lead and calcium along their dynamic trajectory may successfully explain counter-intuitive effects on systemic function and neural behavior which could not be addressed by existing linear models. Our results encourage further efforts towards using nonlinear phenomenology in conjunction with empirically driven system parameters, to obtain a biophysical model able to provide clinical assessments and predictions.

Synergistic protective effect of Beta vulgaris with meso-2,3-dimercaptosuccinic acid against lead-induced neurotoxicity in male rats

“…The Pb capability to substitute for the calcium ions, allowing its passage across the blood-brain barrier and its accumulation in the brain via calcium-ATPase pumps 19 . Where the increasing in Pb intake may lead to the reduction of calcium steady state 34 . Consequently, both the peripheral and central nervous systems are disrupted 34 .…”

“…Where the increasing in Pb intake may lead to the reduction of calcium steady state 34 . Consequently, both the peripheral and central nervous systems are disrupted 34 . This substitution may results in many neurological disorders including mental retardation, brain damage, behavioral problems, and may lead to several diseases like Alzheimer, Parkinson, and Schizophrenia 35 .…”

Effects of Lead on Reproductive Health

“…Prenatal exposure to lead can cause several obstetric complications and adverse pregnancy outcomes [46]. Lead absorbed into the body, mainly by ingestion or inhalation, enters the bloodstream and accumulates in soft organs (mostly in brain, liver, and kidney) and bones [47,48]. It is considered that lead in bone represents approximately 95% of the total body burden in adults [47].…”

“…It is considered that lead in bone represents approximately 95% of the total body burden in adults [47]. During pregnancy, the demand of calcium rises, and lead stored in bone can replace the calcium and recirculate in the bloodstream, becoming an endogenous source of exposure [16,[48][49][50]. Lead from the blood can cross the placenta and impair the development of the fetus [51,52].…”

Potential Antioxidant Activity of Calcium and Selected Oxidative Stress Markers in Lead- and Cadmium-Exposed Workers

“…Pb and Cd exposure affects calcium metabolism in various ways. Furthermore, some studies suggested that calcium levels may have an impact on the blood lead levels [ 23 – 25 ].…”