Related Experiment Video
Updated: Nov 3, 2025
Evaluation of Oxidative Stress in Biological Samples Using the Thiobarbituric Acid Reactive Substances Assay
Published on: May 12, 2020
Effects of human serum albumin on post-mortem changes of malathion
Yoshikazu Yamagishi1,2, Hirotaro Iwase2, Yasumitsu Ogra3,4
1Laboratory of Toxicology and Environmental Health, Graduate School of Pharmaceutical Sciences, Chiba University, Chuo, Chiba, 260-8675, Japan.
Abstract:
Malathion, diethyl 2-[(dimethoxyphosphinothioyl)thio]butanedioate, is one of most widely used organophosphoryl pesticide, and it has been detected in several clinical cases of accidental exposure and suicide. It is reported that the observed malathion concentration in blood of persons who suffer from malathion poisoning is smaller than the expected concentration. Because malathion is bound to human serum albumin (HSA), recovery of malathion in the free form is insufficient. We detected malathion adducts in HSA by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q/TOF-MS). The mass spectra showed that malathion was preferably bound to the lysine (K) and cysteinylproline (CP) residues of HSA. The K- and CP-adducts of malathion were increased in vitro with a dose-dependent fashion when its concentration was smaller than the lethal dose. Further, the K-adduct was also detected in post-mortem blood of an autopsied subject suffering from intentional malathion ingestion. These results suggest that the K-adduct seems to be available to use a biomarker of malathion poisoning, and the determination of the K-adduct could make possible to estimate the amount of malathion ingestion.
Insights
Malathion pesticide exposure is underestimated due to binding to human serum albumin (HSA). Detecting malathion-HSA adducts, particularly the K-adduct, can serve as a reliable biomarker for poisoning and estimate ingestion levels.
Area of Science:
- Toxicology
- Biochemistry
- Analytical Chemistry
Background:
- Malathion is a widely used organophosphate pesticide.
- Malathion poisoning cases often show lower-than-expected blood concentrations.
- Malathion binding to human serum albumin (HSA) complicates accurate quantification.
Purpose of the Study:
- To investigate the binding of malathion to human serum albumin (HSA).
- To identify specific residues of HSA that bind to malathion.
- To evaluate the potential of malathion-HSA adducts as biomarkers for malathion poisoning.
Main Methods:
- Detection of malathion adducts in HSA using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q/TOF-MS).
- In vitro experiments to study the dose-dependent formation of adducts.
- Analysis of post-mortem blood samples for the presence of malathion-HSA adducts.
Main Results:
- Malathion was found to preferentially bind to lysine (K) and cysteinylproline (CP) residues of HSA.
- The formation of K- and CP-adducts increased in a dose-dependent manner in vitro.
- The K-adduct was detected in post-mortem blood from a malathion poisoning victim.
Conclusions:
- Malathion adducts, especially the K-adduct, are formed with HSA.
- The K-adduct can serve as a potential biomarker for malathion poisoning.
- Quantification of the K-adduct may allow for estimation of malathion ingestion amounts.
