Combined exposure to lead, inorganic mercury and methylmercury shows deviation from additivity for cardiovascular toxicity in rats

Abstract

Environmental exposure to metal mixtures in the human population is common. Mixture risk assessments are often challenging because of a lack of suitable data on the relevant mixture. A growing number of studies show an association between lead or mercury exposure and cardiovascular effects. We investigated the cardiovascular effects of single metal exposure or co-exposure to methylmercury [MeHg(I)], inorganic mercury [Hg(II)] and lead [Pb(II)]. Male Wistar rats received four different metal mixtures for 28 days through the drinking water. The ratios of the metals were based on reference and environmental exposure values. Blood and pulse pressure, cardiac output and electrical activity of the heart were selected as end-points. While exposure to only MeHg(I) increased the systolic blood pressure and decreased cardiac output, the effects were reversed with combined exposures (antagonism). In contrast to these effects, combined exposures negatively affected the electrical activity of the heart (synergism). Thus, it appears that estimates of blood total Hg levels need to be paired with estimates of what species of mercury dominate exposure as well as whether lead co-exposure is present to link total blood Hg levels to cardiovascular effects. Based on current human exposure data and our results, there may be an increased risk of cardiac events as a result of combined exposures to Hg(II), MeHg(I) and Pb(II). This increased risk needs to be clarified by analyzing lead and Hg exposure data in relation to cardiac electrical activity in epidemiological studies.

Full Atrioventricular Block Secondary to Acute Poisoning Mercury: A Case Report

“…Other toxic effects are related with different cellular mechanisms, such as; the interruption of microtubule formation, the changing of the intracellular calcium balance and the membrane potential, the alteration of cell membrane integrity, the disturbing or inhibition of enzymes, the inducing of oxidative stress, the inhibition of protein and DNA synthesis, and the disturbing of immune functions [ 18 ]. The vascular effects of mercury include increases in oxidative stress and inflammation [ 19 ], reductions in oxidative defenses [ 20 ], thrombosis [ 21 ], mitochondrial dysfunction [ 22 ], depolarization, autoxidation of the inner infarction [ 10 ], and cardiovascular disease [ 9 , 23 ]. Mercury toxicity is indeed strongly correlated with hypertension, coronary heart disease, myocardial infarction, cardiac arrhythmias, carotid artery obstruction, cerebrovascular accidents, and generalized atherosclerosis [ 9 , 24 ].…”

“…In this respect. Wildeman et al [ 10 ] observed that Hg(II) affects the cardiovascular systems, and they report a prolonged PR interval, mainly by inorganic Hg(II) mercury exposure, as well as showing a significant prolongation of the QRS and QT intervals, suggesting that the electrical activity of the heart might be more susceptible to Hg(II). In his study, the QRS interval, which represents the depolarization of the ventricles, was most sensitive to combined metal exposure.…”

“…For decades, the toxic effects of mercury were associated mainly with the central nervous system. However, a growing body of evidence suggests that mercury exposure can also lead to increased risks of adverse cardiovascular impacts in exposed populations [ 9 ], mainly by organic and inorganic mercury exposure [ 10 ].…”

Synergistic Effects of Heavy Metals and Pesticides in Living Systems

“…Combined administration of Cd with nickel may produce fewer pathological alterations than that of Cd alone (İşcan et al, 2002 ). The synergistic effect of lead (Pb) and mercury (Hg) are extremely neurotoxic and has been reported to be much worse than the single one (Wildemann et al, 2015 ). The amount of mercury as well as lead sufficient to kill 1% of rats when administered individually, when administered in the combined may kill 100% of rats tested ( http://amalgam.org/education/scientific-evidenceresearch/synergistic-effects-of-mercury-other-toxic-exposures/ ) (Sheets and Sheet, 2018 ).…”

Lead Induced Ototoxicity and Neurotoxicity in Adult Guinea Pig

“…Lead accumulation in the body can lead to irreversible dysfunction in multiple systems [1–3]. Many studies have shown that lead exposure can cause or aggravate hearing damage in human or animals [4–6]. Lead exposure experiments in C57BL/6 mice by Samson Jamesdanie proved that lead exposure could damage the inner ear barrier, activate the oxidative stress pathway in the mouse cochlea, and significantly alter hearing threshold [7].…”