TY - JOUR
T1 - The Organophosphate paraoxon and its antidote obidoxime inhibit thrombin activity and affect coagulation in vitro
AU - Golderman, Valery
AU - Shavit-Stein, Efrat
AU - Tamarin, Ilia
AU - Rosman, Yossi
AU - Shrot, Shai
AU - Rosenberg, Nurit
AU - Maggio, Nicola
AU - Chapman, Joab
AU - Eisenkraft, Arik
N1 - Publisher Copyright:
© 2016 Golderman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/9
Y1 - 2016/9
N2 - Organophosphates (OPs) are potentially able to affect serine proteases by reacting with their active site. The potential effects of OPs on coagulation factors such as thrombin and on coagulation tests have been only partially characterized and potential interactions with OPs antidotes such as oximes and muscarinic blockers have not been addressed. In the current study, we investigated the in vitro interactions between coagulation, thrombin, the OP paraoxon, and its antidotes obidoxime and atropine. The effects of these substances on thrombin activity were measured in a fluorescent substrate and on coagulation by standard tests. Both paraoxon and obidoxime but not atropine significantly inhibited thrombin activity, and prolonged prothrombin time, thrombin time, and partial thromboplastin time. When paraoxon and obidoxime were combined, a significant synergistic effect was found on both thrombin activity and coagulation tests. In conclusion, paraoxon and obidoxime affect thrombin activity and consequently alter the function of the coagulation system. Similar interactions may be clinically relevant for coagulation pathways in the blood and possibly in the brain.
AB - Organophosphates (OPs) are potentially able to affect serine proteases by reacting with their active site. The potential effects of OPs on coagulation factors such as thrombin and on coagulation tests have been only partially characterized and potential interactions with OPs antidotes such as oximes and muscarinic blockers have not been addressed. In the current study, we investigated the in vitro interactions between coagulation, thrombin, the OP paraoxon, and its antidotes obidoxime and atropine. The effects of these substances on thrombin activity were measured in a fluorescent substrate and on coagulation by standard tests. Both paraoxon and obidoxime but not atropine significantly inhibited thrombin activity, and prolonged prothrombin time, thrombin time, and partial thromboplastin time. When paraoxon and obidoxime were combined, a significant synergistic effect was found on both thrombin activity and coagulation tests. In conclusion, paraoxon and obidoxime affect thrombin activity and consequently alter the function of the coagulation system. Similar interactions may be clinically relevant for coagulation pathways in the blood and possibly in the brain.
UR - http://www.scopus.com/inward/record.url?scp=84992195781&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0163787
DO - 10.1371/journal.pone.0163787
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AN - SCOPUS:84992195781
SN - 1932-6203
VL - 11
JO - PLoS ONE
JF - PLoS ONE
IS - 9
M1 - e0163787
ER -