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The Organophosphate Paraoxon and Its Antidote Obidoxime Inhibit Thrombin Activity and Affect Coagulation In Vitro

Valery Golderman1, Efrat Shavit-Stein2, Ilia Tamarin3

  • 1Laboratory for Neurological Research, Sheba Medical Center, Tel HaShomer, Israel.

Plos One
|October 1, 2016
PubMed

Insights

Organophosphates and their antidote obidoxime inhibit thrombin activity and affect blood coagulation. This interaction may have clinical relevance for coagulation pathways in the body and brain.

Area of Science:

  • Biochemistry
  • Toxicology
  • Pharmacology

Background:

  • Organophosphates (OPs) can interact with serine proteases.
  • The effects of OPs and their antidotes on coagulation factors, particularly thrombin, are not fully understood.

Purpose of the Study:

  • To investigate in vitro interactions between paraoxon (an OP), its antidotes (obidoxime and atropine), and the coagulation system.
  • To assess the impact on thrombin activity and standard coagulation tests.

Main Methods:

  • Measurement of thrombin activity using a fluorescent substrate.
  • Evaluation of coagulation using standard coagulation tests (prothrombin time, thrombin time, partial thromboplastin time).

Main Results:

  • Paraoxon and obidoxime significantly inhibited thrombin activity.
  • Both paraoxon and obidoxime prolonged prothrombin time, thrombin time, and partial thromboplastin time.
  • A synergistic inhibitory effect on thrombin and coagulation was observed when paraoxon and obidoxime were combined.

Conclusions:

  • Paraoxon and obidoxime directly affect thrombin activity.
  • These substances alter the function of the coagulation system.
  • Potential clinical relevance for coagulation pathways in the blood and brain warrants further investigation.

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