Toxicity assessment due to prenatal and lactational exposure to lead, cadmium and mercury mixtures

The heavy metals lead (Pb), cadmium (Cd) and mercury (Hg) are common environmental pollutants that can be detected simultaneously in blood, serum, and urine samples from the general human population. However, there is limited information regarding toxicity of low-level exposure to Pb, Cd, and Hg mixtures. Our previous research showed the interaction of these three elements at low concentrations in vitro. In this study, we further evaluate early effects of low dose exposure to Pb, Cd, and Hg mixtures on the brain, heart, liver, kidney, and testicle in rats. Pregnant rats were exposed to various concentrations of heavy metal mixtures (MM) in drinking water, during gestation and lactation, and the impacts on offspring were measured at postnatal day 23. Our results showed that the concentrations of Pb, Cd, and Hg in the blood of rat pups were similar to those in the blood of the general human population. Additionally, the MM concentrations in their blood and brain significantly increased in a dose-dependent manner. MM exposure caused histopathological changes in the brain, liver, kidney and testicle. Statistically significant increases in liver CYP450 and PON1, kidney KIM1, and decrease in testicle SDH were observed. In the brain, significant increases were detected in oxidative stress, intracellular free calcium, and cell apoptosis. Further neurobehavioral testing revealed that MM exposure caused dose-dependent impairments in learning and memory as well as sensory perception. MM exposure also disrupted synapse remodeling, which may be associated with pathways involved in dendritic spine growth, maintenance, and elimination. These results suggested that exposure to Pb, Cd, and Hg mixtures, at human environmental exposure related levels, caused damage to multiple organs as well as impairments in neurobehavioral functions of rats. Our findings emphasize the need to control and regulate potential sources of heavy metal contamination.