Effects of combined arsenic and lead exposure on the brain monoaminergic system and behavioral functions in rats: Reversal effect of MiADMSA

In this study, we evaluated the therapeutic efficacy of monoisoamyldimercaptosuccinic acid (MiADMSA) against individual and combined effects of arsenic (As) and lead (Pb) on the monoaminergic system and behavioral functions in rats. Pregnant rats were exposed to sodium metaarsenite (50 ppm) and lead acetate (0.2%) individually and in combination (As = 25 ppm + Pb = 0.1%) via drinking water from gestation day (GD) 6 to postnatal day (PND) 21. MiADMSA (50 mg/kg body weight) was given orally through gavage for 3 consecutive days to pups from PND 18 to PND 20. The results showed increases in synaptosomal epinephrine, dopamine, and norepinephrine levels with individual metal exposures and decreases with combined exposure to As and Pb in the cortex, cerebellum, and hippocampus in PND 21, PND 28, and 3 months age-group rats. We found decreased activity of mitochondrial monoamine oxidase in the selected brain regions following individual and combined exposures to Pb and As. In addition, rats treated with Pb and As alone or in combination showed significant deficits in open-field behavior, grip strength, locomotor activity, and exploratory behavior at PND 28 and 3 months of age. However, MiADMSA administration showed reversal effects against the As- and/or Pb-induced impairments in the monoaminergic system as well as in behavioral functions of rats. Our data demonstrated that the mixture of Pb and As induced synergistic toxicity to developing brain leading to impairments in neurobehavioral functions and also suggest therapeutic efficacy of MiADMSA against Pb- and/or As-induced developmental neurotoxicity