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Plasma metabolic profiling analysis of toxicity induced by brodifacoum using metabonomics coupled with multivariate

Hui Yan1, Zheng Qiao2, Baohua Shen2

  • 1Department of Forensic Toxicology, Institute of Forensic Sciences, Ministry of Justice, Shanghai Key Laboratory of Forensic Medicine, Shanghai 200063, China; Department of Forensic Science, Shanghai Medical College, Fudan University, Shanghai 200032, China.

Forensic Science International
|September 7, 2016
PubMed

Insights

Brodifacoum rodenticide poisoning causes dose-dependent toxicity, affecting glucose, lipid, and amino acid metabolism. Metabonomics analysis identified 24 plasma metabolites as potential biomarkers for brodifacoum toxicity.

Area of Science:

  • Toxicology
  • Metabonomics
  • Biomarker Discovery

Background:

  • Brodifacoum is a widely used rodenticide, but human and animal poisoning is a significant concern.
  • While brodifacoum toxicity is documented, its precise mechanisms require further elucidation.
  • Understanding brodifacoum's toxicological pathways is crucial for risk assessment and management.

Purpose of the Study:

  • To characterize the metabolic profile of brodifacoum-induced toxicity in rat plasma.
  • To identify potential plasma biomarkers indicative of brodifacoum poisoning.
  • To explore the underlying mechanisms of brodifacoum toxicity using a metabonomics approach.

Main Methods:

  • Gas chromatography-mass spectrometry (GC-MS) and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) were employed for metabolic profiling.
  • Rat plasma samples were analyzed to assess the metabolic changes following brodifacoum exposure.
  • Dose-dependent toxicity was evaluated, and blood brodifacoum concentrations were correlated with ingestion doses.

Main Results:

  • Brodifacoum toxicity was dose-dependent, with subcutaneous hemorrhage observed in high-dose groups.
  • A positive correlation was found between blood brodifacoum concentration and ingestion dose.
  • Twenty-four metabolites showed significant changes, primarily related to glucose, lipid, and amino acid metabolism, indicating anticoagulant activity, nephrotoxicity, and hepatic damage.

Conclusions:

  • MS-based metabonomics analysis of plasma is effective for identifying potential brodifacoum poisoning biomarkers.
  • The identified metabolic changes provide insights into the mechanisms of brodifacoum-induced toxicity.
  • This study contributes to a better understanding of brodifacoum's toxicological effects and aids in the development of diagnostic markers.
Keywords:
BrodifacoumMass spectrometryMetabonomicsPlasmaToxicity

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