Abstract
Thousands suffer poisonous snake bite, often from defibrinogenating species annually. Three rattlesnake species in particular, the timber rattlesnake, Eastern diamondback rattlesnake, and Southern Pacific rattlesnake, cause clinically relevant hypofibrinogenemia via thrombin-like activity in their venom. It has been demonstrated that iron (Fe) and carbon monoxide (CO) change the ultrastructure of plasma thrombi and improve coagulation kinetics. Thus, the present investigation sought to determine if pretreatment of plasma with Fe and CO could attenuate venom-mediated catalysis of fibrinogen via thrombin-like activity. Human plasma was pretreated with ferric chloride (0-10 μM) and CO-releasing molecule-2 (0-100 μM) prior to exposure to 2.5-10 μg/ml of venom obtained from the aforementioned three species of rattlesnake. Coagulation kinetics were determined with thrombelastography. All three snake venoms degraded plasmatic coagulation kinetics to a significant extent, especially diminishing the speed of clot growth and strength. Pretreatment of plasma with Fe and CO completely abrogated the effects of all three venoms on coagulation kinetics. Further in vitro investigation of other pit viper venoms that possess thrombin-like activity is indicated to see if there is significant conservation of venom enzymatic target recognition of specific amino acid sequences such that Fe and CO can reliably attenuate venom-mediated catalysis of fibrinogen. These data also serve as a rationale for future preclinical investigation.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1116-1122 |
| Number of pages | 7 |
| Journal | Human and Experimental Toxicology |
| Volume | 35 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 1 2016 |
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Keywords
- carbon monoxide
- fibrinogen
- iron
- Snake venom
- thrombelastography
- thrombin
ASJC Scopus subject areas
- Toxicology
- Health, Toxicology and Mutagenesis
Cite this
Iron and carbon monoxide prevent degradation of plasmatic coagulation by thrombin-like activity in rattlesnake venom. / Nielsen, Vance G.
In: Human and Experimental Toxicology, Vol. 35, No. 10, 01.10.2016, p. 1116-1122.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Iron and carbon monoxide prevent degradation of plasmatic coagulation by thrombin-like activity in rattlesnake venom
AU - Nielsen, Vance G
PY - 2016/10/1
Y1 - 2016/10/1
N2 - Thousands suffer poisonous snake bite, often from defibrinogenating species annually. Three rattlesnake species in particular, the timber rattlesnake, Eastern diamondback rattlesnake, and Southern Pacific rattlesnake, cause clinically relevant hypofibrinogenemia via thrombin-like activity in their venom. It has been demonstrated that iron (Fe) and carbon monoxide (CO) change the ultrastructure of plasma thrombi and improve coagulation kinetics. Thus, the present investigation sought to determine if pretreatment of plasma with Fe and CO could attenuate venom-mediated catalysis of fibrinogen via thrombin-like activity. Human plasma was pretreated with ferric chloride (0-10 μM) and CO-releasing molecule-2 (0-100 μM) prior to exposure to 2.5-10 μg/ml of venom obtained from the aforementioned three species of rattlesnake. Coagulation kinetics were determined with thrombelastography. All three snake venoms degraded plasmatic coagulation kinetics to a significant extent, especially diminishing the speed of clot growth and strength. Pretreatment of plasma with Fe and CO completely abrogated the effects of all three venoms on coagulation kinetics. Further in vitro investigation of other pit viper venoms that possess thrombin-like activity is indicated to see if there is significant conservation of venom enzymatic target recognition of specific amino acid sequences such that Fe and CO can reliably attenuate venom-mediated catalysis of fibrinogen. These data also serve as a rationale for future preclinical investigation.
AB - Thousands suffer poisonous snake bite, often from defibrinogenating species annually. Three rattlesnake species in particular, the timber rattlesnake, Eastern diamondback rattlesnake, and Southern Pacific rattlesnake, cause clinically relevant hypofibrinogenemia via thrombin-like activity in their venom. It has been demonstrated that iron (Fe) and carbon monoxide (CO) change the ultrastructure of plasma thrombi and improve coagulation kinetics. Thus, the present investigation sought to determine if pretreatment of plasma with Fe and CO could attenuate venom-mediated catalysis of fibrinogen via thrombin-like activity. Human plasma was pretreated with ferric chloride (0-10 μM) and CO-releasing molecule-2 (0-100 μM) prior to exposure to 2.5-10 μg/ml of venom obtained from the aforementioned three species of rattlesnake. Coagulation kinetics were determined with thrombelastography. All three snake venoms degraded plasmatic coagulation kinetics to a significant extent, especially diminishing the speed of clot growth and strength. Pretreatment of plasma with Fe and CO completely abrogated the effects of all three venoms on coagulation kinetics. Further in vitro investigation of other pit viper venoms that possess thrombin-like activity is indicated to see if there is significant conservation of venom enzymatic target recognition of specific amino acid sequences such that Fe and CO can reliably attenuate venom-mediated catalysis of fibrinogen. These data also serve as a rationale for future preclinical investigation.
KW - carbon monoxide
KW - fibrinogen
KW - iron
KW - Snake venom
KW - thrombelastography
KW - thrombin
UR - http://www.scopus.com/inward/record.url?scp=84986582215&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84986582215&partnerID=8YFLogxK
U2 - 10.1177/0960327115621366
DO - 10.1177/0960327115621366
M3 - Article
C2 - 26666988
AN - SCOPUS:84986582215
VL - 35
SP - 1116
EP - 1122
JO - Human and Experimental Toxicology
JF - Human and Experimental Toxicology
SN - 0960-3271
IS - 10
ER -