Post-mortem interaction between methidathion and human serum albumin in blood
Yoshikazu Yamagishi1, Sayaka Nagasawa1,2, Hirotaro Iwase1,3
1Department of Legal Medicine, Graduate School of Medicine, Chiba University.
Abstract:
Methidathion [3-(dimethoxyphosphinothioylsulfanylmethyl)-5-methoxy-1,3,4-thiadiazol-2-one; hereinafter DMTP], one of the most widely used organophosphorus pesticides, has been detected in some clinical cases of accidental exposure and suicide in Japan. It has been reported that DMTP concentration is decreased in blood. In this study, it is difficult to recover DMTP in the free form because DMTP is bound to human serum albumin (HSA). We detected DMTP adducts in HSA by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q/TOF-MS). The mass spectra showed that DMTP was preferably bound to the lysine (K), tyrosine (Y), and cysteinylproline (CP) residues of HSA. The concentrations of K-adduct, DMTP-Y-adduct and DMTP-CP-adduct were increased in vitro in a dose-dependent fashion when DMTP concentration was lower than the lethal dose. Furthermore, the DMTP-Y-adduct and DMTP-CP-adduct were also detected in post-mortem blood of an autopsied subject who died by intentional DMTP ingestion. The results suggested that the DMTP-Y-adduct and DMTP-CP-adduct could be used as a biomarker of DMTP poisoning, and the decrease concentration of DMTP in blood after death could be determined on the basis of the concentration of the DMTP-CP-adduct in blood.
Insights
Methidathion (DMTP) pesticide binds to human serum albumin (HSA) in blood. DMTP-tyrosine and DMTP-cysteinylproline adducts in HSA can serve as biomarkers for DMTP poisoning.
Area of Science:
- Toxicology
- Biochemistry
- Analytical Chemistry
Background:
- Methidathion (DMTP) is a widely used organophosphorus pesticide.
- DMTP has been detected in clinical cases of accidental exposure and suicide.
- DMTP concentration decreases in blood post-mortem, making free DMTP difficult to detect.
Purpose of the Study:
- To investigate the binding of DMTP to human serum albumin (HSA).
- To identify potential biomarkers for DMTP poisoning.
- To understand DMTP degradation in post-mortem blood.
Main Methods:
- Liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q/TOF-MS) was used to detect DMTP adducts in HSA.
- In vitro experiments assessed DMTP binding to HSA residues.
- Analysis of post-mortem blood from a DMTP ingestion victim.
Main Results:
- DMTP preferentially binds to lysine (K), tyrosine (Y), and cysteinylproline (CP) residues of HSA.
- DMTP-K, DMTP-Y, and DMTP-CP adducts increased dose-dependently in vitro.
- DMTP-Y and DMTP-CP adducts were detected in post-mortem blood.
Conclusions:
- DMTP-Y-adduct and DMTP-CP-adduct are potential biomarkers for DMTP poisoning.
- DMTP-CP adduct concentration can help determine DMTP levels in post-mortem blood.
- This study elucidates DMTP-HSA interactions and their toxicological implications.
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