Search

Cadmium(Cd) and chlorpyrifos (CPF) are widespread harmful environmentalpollutants with neurotoxicity to mammals. Although the exposure toCd and CPF at the same time may pose a significant risk to human health,the subchronic combined neurotoxicity of these two chemicals at lowlevels in the brain is poorly understood. In this study, we treatedrats with three doses (low, middle, and high) of Cd, CPF, or theirmixture for 90 days. No obvious symptom was observed in the treatedanimals except those treated with high-dose CPF. Histological resultsshowed that middle and high doses of the chemicals caused neuronalcell damage in brains. GC–MS-based metabonomics analysis revealedthat energy and amino acid metabolism were disturbed in the brainsof rats exposed to the two chemicals and their combinations even atlow doses. We further identified the unique brain metabolite biomarkersfor rats treated with Cd, CPF, or both. Two amino acids, tyrosineand l-leucine, were identified as the biomarkers for Cd andCPF treatment, respectively. In addition, a set of five unique biomarkers(1,2-propanediol-1-phosphate, d-gluconic acid, 9H-purine, serine, and 2-ketoisovaleric acid) was identified for themixtures of Cd and CPF. Therefore, the metabolomics analysis is moresensitive than regular clinical observation and pathological examinationfor detecting the neurotoxicity of the individual and combined Cdand CPF at low levels. Overall, these results identified the uniquebiomarkers for Cd and CPF exposure, which provide new insights intothe mechanism of their joint toxicity. [ABSTRACT FROM AUTHOR]