title: Metabolomics analysis and biomarker identification for brains of rats exposed subchronically to the mixtures of low-dose cadmium and chlorpyrifos.
abstract: Cadmium (Cd) and chlorpyrifos (CPF) are widespread harmful environmental pollutants with neurotoxicity to mammals. Although the exposure to Cd and CPF at the same time may pose a significant risk to human health, the subchronic combined neurotoxicity of these two chemicals at low levels in the brain is poorly understood. In this study, we treated rats with three doses (low, middle, and high) of Cd, CPF, or their mixture for 90 days. No obvious symptom was observed in the treated animals except those treated with high-dose CPF. Histological results showed that middle and high doses of the chemicals caused neuronal cell damage in brains. GC-MS-based metabonomics analysis revealed that energy and amino acid metabolism were disturbed in the brains of rats exposed to the two chemicals and their combinations even at low doses. We further identified the unique brain metabolite biomarkers for rats treated with Cd, CPF, or both. Two amino acids, tyrosine and l-leucine, were identified as the biomarkers for Cd and CPF 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 the mixtures of Cd and CPF. Therefore, the metabolomics analysis is more sensitive than regular clinical observation and pathological examination for detecting the neurotoxicity of the individual and combined Cd and CPF at low levels. Overall, these results identified the unique biomarkers for Cd and CPF exposure, which provide new insights into the mechanism of their joint toxicity.
authors: †Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1-5 Beichenxi Road, Beijing 100101, P. R. China.|§University of Chinese Academy of Sciences, Beijing 100049, P. R. China.
authors: Ming-Yuan
authors: MY
authors: Xu
authors: †Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1-5 Beichenxi Road, Beijing 100101, P. R. China.|‡Department of Veterinary Medicine and Animal Science, Beijing University of Agriculture, Beijing 102206, P. R. China.
authors: Ying-Jian
authors: YJ
authors: Sun
authors: †Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1-5 Beichenxi Road, Beijing 100101, P. R. China.
authors: Pan
authors: P
authors: Wang
authors: †Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1-5 Beichenxi Road, Beijing 100101, P. R. China.
authors: Hai-Yang
authors: HY
authors: Xu
authors: †Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1-5 Beichenxi Road, Beijing 100101, P. R. China.
authors: Li-Ping
authors: LP
authors: Chen
authors: †Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1-5 Beichenxi Road, Beijing 100101, P. R. China.
authors: Li
authors: L
authors: Zhu
authors: †Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1-5 Beichenxi Road, Beijing 100101, P. R. China.
authors: Yi-Jun
authors: YJ
authors: Wu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D002104:Cadmium / Q000008:administration & dosage* / Q000633:toxicity*; D004390:Chlorpyrifos / Q000008:administration & dosage* / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D007930:Leucine / Q000032:analysis / Q000378:metabolism; D008297:Male; D055432:Metabolomics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000032:analysis / Q000378:metabolism
chemical_list: D015415:Biomarkers; D002104:Cadmium; D014443:Tyrosine; D007930:Leucine; D004390:Chlorpyrifos