Abstract

Chlorpyrifos (CPF) and cadmium (Cd) are widespread environmental pollutants, which are often present in drinking water and foods. However, the combined effects of CPF and Cd were not entirely clear at present. There was also no biomarker available to diagnose the poisoning of the two chemicals at low dose for long-term exposures. In this study, we investigated the change of serum metabolites of rats with subchronic exposure to CPF, Cd, and CPF plus Cd using gas chromatography-mass spectrometer-based metabolomics approach. We performed a stepwise optimization algorithm based on receiver operating characteristic to identify serum metabolite biomarkers for toxic diagnosis of the chemicals at different doses after 90-day exposure. We found that aminomalonic acid was the biomarker for the toxicity of Cd alone administration, and serine and propanoic acid were unique biomarkers for the toxicities of CPF plus Cd administrations. Our results suggest that subchronic exposure to CPF and Cd alone, or in combination at their low doses, could cause disturbance of energy and amino acid metabolism. Overall, we have shown that analysis of serum metabolomics can make exceptional contributions to the understanding of the toxic effects following long-term low-dose exposure of the organophosphorus pesticide and heavy metal.

Highlights

  • Chlorpyrifos (CPF) and cadmium (Cd) are widespread environmental pollutants, which are often present in drinking water and foods

  • We found that CPF and Cd disturbed energy and amino acids metabolism in the brain and liver

  • AST and total bilirubin (TBIL) levels increased in most of the rats treated with CPF plus Cd, but ALT levels increased only in the rats exposed to the high-dose mixture of CPF and Cd

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Summary

Introduction

Chlorpyrifos (CPF) and cadmium (Cd) are widespread environmental pollutants, which are often present in drinking water and foods. Our results suggest that subchronic exposure to CPF and Cd alone, or in combination at their low doses, could cause disturbance of energy and amino acid metabolism. Chronic Cd exposure induces toxicity in kidneys, liver, and bones[5,6,7,8] Due to their toxicity to different target organs, CPF and Cd pose significant threats to public health. Metabolomics is a very useful approach for toxicological studies because it can characterize the changes of metabolite levels induced by toxic chemicals and identify the specific biomarkers for each toxicant[17,18]. We aim to use metabolomics analysis in serum to study the combined toxicity of CPF and Cd and identify potential biomarkers for their exposure. We use the gas chromatography - mass spectrometer (GC/MS) method, which has high sensitivity and specificity for detecting and quantification of chemicals in biofluids and tissue extracts[19]

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