Plasma metabolic profiling analysis of toxicity induced by brodifacoum using metabonomics coupled with multivariate data analysis.
Brodifacoum is one of the most widely used rodenticides for rodent control and eradication; however, human and animal poisoning due to primary and secondary exposure has been reported since its development. Although numerous studies have described brodifacoum induced toxicity, the precise mechanism still needs to be explored. Gas chromatography mass spectrometry (GC-MS) coupled with an ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was applied to characterize the metabolic profile of brodifacoum induced toxicity and discover potential biomarkers in rat plasma. The toxicity of brodifacoum was dose-dependent, and the high-dose group obviously manifested toxicity with subcutaneous hemorrhage. The blood brodifacoum concentration showed a positive relation to the ingestion dose in toxicological analysis. Significant changes of twenty-four metabolites were identified and considered as potential toxicity biomarkers, primarily involving glucose metabolism, lipid metabolism and amino acid metabolism associated with anticoagulant activity, nephrotoxicity and hepatic damage. MS-based metabonomics analysis in plasma samples is helpful to search for potential poisoning biomarkers and to understand the underlying mechanisms of brodifacoum induced toxicity.
Department 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.
Hui
H
Yan
Department of Forensic Toxicology, Institute of Forensic Sciences, Ministry of Justice, Shanghai Key Laboratory of Forensic Medicine, Shanghai 200063, China.
Zheng
Z
Qiao
Department of Forensic Toxicology, Institute of Forensic Sciences, Ministry of Justice, Shanghai Key Laboratory of Forensic Medicine, Shanghai 200063, China.
Baohua
B
Shen
Department of Forensic Toxicology, Institute of Forensic Sciences, Ministry of Justice, Shanghai Key Laboratory of Forensic Medicine, Shanghai 200063, China.
Ping
P
Xiang
Department of Forensic Toxicology, Institute of Forensic Sciences, Ministry of Justice, Shanghai Key Laboratory of Forensic Medicine, Shanghai 200063, China. Electronic address: minshensfjd@hotmail.com.
Min
M
Shen
D015110:4-Hydroxycoumarins / Q000097:blood* / Q000633:toxicity*; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002853:Chromatography, Liquid; D016002:Discriminant Analysis; D008401:Gas Chromatography-Mass Spectrometry; D005947:Glucose / Q000378:metabolism; D050356:Lipid Metabolism; D055432:Metabolomics; D015999:Multivariate Analysis; D025341:Principal Component Analysis; D017208:Rats, Wistar; D012378:Rodenticides / Q000097:blood* / Q000633:toxicity*; D053719:Tandem Mass Spectrometry
D015110:4-Hydroxycoumarins; D000596:Amino Acids; D012378:Rodenticides; C013418:bromfenacoum; D005947:Glucose
Brodifacoum; Mass spectrometry; Metabonomics; Plasma; Toxicity