In vivo Monitoring Metabolite profiles of Acrylamide
Date Issued
2012
Date
2012
Author(s)
Luo, Yu-Syuan
Abstract
Acrylamide is a potential human carcinogen and widely existed in high temperature processed foods. As a result, the long-term exposure of acrylamide on food safety issue has been concerned. Previous studies suggested that metabolic activation of acrylamide to glycidamide might be responsible for its genotoxicity. Meanwhile, acrylamide and glycidamide would be detoxified by glutathione transferase to acrylamide- and glycidamide-glutathione adducts, and glycidamide can be spontaneously hydrolyzed or detoxified by epoxide hydrolase to glyceramide. This study is aimed to reveal acrylamide metabonomics in blood of Sprague-Dawley rats, including acrylamide, glycidamide, glyceramide, acrylamide-glutathione adducts (AA-GSH), glycidamide-glutathione adducts(GA-GSH), with an automated in vivo microdialysis isotope-dilution solid-phase extraction LC-MS/MS method. Results from this study can provide critical quantitative information of acrylamide metabolism in SD rats. Anaesthetized rats were treated with acrylamide of 0.1mg/kg and 5mg/kg by I.P. injection, respectively. Real-time acrylamide metabolites were profiled with an automated isotope-dilution column-switching LC-MS/MS method. The elimination rate constant (ke) was 0.26 hr-1 for AA and 0.23 hr-1 for AA-GSH and the half life (T1/2) was 2.67 hr for AA and 2.97 hr for AA-GSH in rats treated with 0.1 mg/kg. Ke of AA, AA-GSH and GA were 0.23, 0.2 and 0.14 hr-1, and T1/2 were 2.97, 3.52 and 4.9 hr for AA, AA-GSH and GA in rats treated with 5 mg/kg, respectively. Estimated with their area under curve (AUC), the AA, GA and AA-GSH account for 86.1%, 8% and 1% , respectively. This study reveals that the majority of absorbed AA is metabolically activated to GA.
Subjects
Acrylamide
Glutathione
Metabonomics
LC-MS/MS
In vivo microdialysis
Type
thesis
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