Iron protects porcine plasma coagulation kinetics from degradation by Crotalus atrox venom

Christine S. Olver, Vance G Nielsen

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

While the administration of antivenom to treat hemotoxic snake bite injury remains the gold standard of therapy, we have demonstrated that modifying human fibrinogen with iron and carbon monoxide renders it resistant to fibrinogenolytic snake venom enzymes. In order to translate these findings into a possible biometal-based therapy complementary to antivenom administration, a preclinical model that possesses fibrinogen that closely mimics the human molecule in response to iron and carbon monoxide needed to be identified. The goal of this investigation was to determine if a swine model could serve in this capacity by assessing the thrombelastographic response of porcine plasma to iron and carbon monoxide exposure, without or with further exposure to the fibrinogenolytic venom of the viper Crotalus atrox. Using plasma obtained from eight swine, it was determined that their plasma responded to iron and carbon monoxide in a manner similar to that of human plasma by displaying enhanced coagulation kinetics. However, in sharp contrast to the response seen with human plasma, only iron significantly protected porcine plasma coagulation kinetics from C. atrox venom degradation. Therefore the pig is an animal beyond humans that could derive benefit from the biometal-focused therapy of iron infusion to protect against venom mediated compromise of coagulation. Thus, future investigation to assess the effects of iron administration to attenuate the effects of fibrinogenolytic envenomation with a pig model is justified.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalBioMetals
DOIs
StateAccepted/In press - Jul 19 2017

Fingerprint

Crotalus atrox
Crotalus
Venoms
venoms
Coagulation
coagulation
Swine
Iron
iron
carbon monoxide
Plasmas
kinetics
Degradation
swine
Kinetics
Carbon Monoxide
degradation
Carbon monoxide
antivenoms
Plasma (human)

Keywords

  • Carbon monoxide
  • Fibrinogen
  • Iron
  • Metalloproteinase
  • Porcine
  • Thrombelastography

ASJC Scopus subject areas

  • Biomaterials
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Metals and Alloys

Cite this

Iron protects porcine plasma coagulation kinetics from degradation by Crotalus atrox venom. / Olver, Christine S.; Nielsen, Vance G.

In: BioMetals, 19.07.2017, p. 1-7.

Research output: Contribution to journalArticle

@article{b259c2ece13b411ab2672bec7b71d583,
title = "Iron protects porcine plasma coagulation kinetics from degradation by Crotalus atrox venom",
abstract = "While the administration of antivenom to treat hemotoxic snake bite injury remains the gold standard of therapy, we have demonstrated that modifying human fibrinogen with iron and carbon monoxide renders it resistant to fibrinogenolytic snake venom enzymes. In order to translate these findings into a possible biometal-based therapy complementary to antivenom administration, a preclinical model that possesses fibrinogen that closely mimics the human molecule in response to iron and carbon monoxide needed to be identified. The goal of this investigation was to determine if a swine model could serve in this capacity by assessing the thrombelastographic response of porcine plasma to iron and carbon monoxide exposure, without or with further exposure to the fibrinogenolytic venom of the viper Crotalus atrox. Using plasma obtained from eight swine, it was determined that their plasma responded to iron and carbon monoxide in a manner similar to that of human plasma by displaying enhanced coagulation kinetics. However, in sharp contrast to the response seen with human plasma, only iron significantly protected porcine plasma coagulation kinetics from C. atrox venom degradation. Therefore the pig is an animal beyond humans that could derive benefit from the biometal-focused therapy of iron infusion to protect against venom mediated compromise of coagulation. Thus, future investigation to assess the effects of iron administration to attenuate the effects of fibrinogenolytic envenomation with a pig model is justified.",
keywords = "Carbon monoxide, Fibrinogen, Iron, Metalloproteinase, Porcine, Thrombelastography",
author = "Olver, {Christine S.} and Nielsen, {Vance G}",
year = "2017",
month = "7",
day = "19",
doi = "10.1007/s10534-017-0035-9",
language = "English (US)",
pages = "1--7",
journal = "BioMetals",
issn = "0966-0844",
publisher = "Springer Netherlands",

}

TY - JOUR

T1 - Iron protects porcine plasma coagulation kinetics from degradation by Crotalus atrox venom

AU - Olver, Christine S.

AU - Nielsen, Vance G

PY - 2017/7/19

Y1 - 2017/7/19

N2 - While the administration of antivenom to treat hemotoxic snake bite injury remains the gold standard of therapy, we have demonstrated that modifying human fibrinogen with iron and carbon monoxide renders it resistant to fibrinogenolytic snake venom enzymes. In order to translate these findings into a possible biometal-based therapy complementary to antivenom administration, a preclinical model that possesses fibrinogen that closely mimics the human molecule in response to iron and carbon monoxide needed to be identified. The goal of this investigation was to determine if a swine model could serve in this capacity by assessing the thrombelastographic response of porcine plasma to iron and carbon monoxide exposure, without or with further exposure to the fibrinogenolytic venom of the viper Crotalus atrox. Using plasma obtained from eight swine, it was determined that their plasma responded to iron and carbon monoxide in a manner similar to that of human plasma by displaying enhanced coagulation kinetics. However, in sharp contrast to the response seen with human plasma, only iron significantly protected porcine plasma coagulation kinetics from C. atrox venom degradation. Therefore the pig is an animal beyond humans that could derive benefit from the biometal-focused therapy of iron infusion to protect against venom mediated compromise of coagulation. Thus, future investigation to assess the effects of iron administration to attenuate the effects of fibrinogenolytic envenomation with a pig model is justified.

AB - While the administration of antivenom to treat hemotoxic snake bite injury remains the gold standard of therapy, we have demonstrated that modifying human fibrinogen with iron and carbon monoxide renders it resistant to fibrinogenolytic snake venom enzymes. In order to translate these findings into a possible biometal-based therapy complementary to antivenom administration, a preclinical model that possesses fibrinogen that closely mimics the human molecule in response to iron and carbon monoxide needed to be identified. The goal of this investigation was to determine if a swine model could serve in this capacity by assessing the thrombelastographic response of porcine plasma to iron and carbon monoxide exposure, without or with further exposure to the fibrinogenolytic venom of the viper Crotalus atrox. Using plasma obtained from eight swine, it was determined that their plasma responded to iron and carbon monoxide in a manner similar to that of human plasma by displaying enhanced coagulation kinetics. However, in sharp contrast to the response seen with human plasma, only iron significantly protected porcine plasma coagulation kinetics from C. atrox venom degradation. Therefore the pig is an animal beyond humans that could derive benefit from the biometal-focused therapy of iron infusion to protect against venom mediated compromise of coagulation. Thus, future investigation to assess the effects of iron administration to attenuate the effects of fibrinogenolytic envenomation with a pig model is justified.

KW - Carbon monoxide

KW - Fibrinogen

KW - Iron

KW - Metalloproteinase

KW - Porcine

KW - Thrombelastography

UR - http://www.scopus.com/inward/record.url?scp=85025088012&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85025088012&partnerID=8YFLogxK

U2 - 10.1007/s10534-017-0035-9

DO - 10.1007/s10534-017-0035-9

M3 - Article

C2 - 28726133

AN - SCOPUS:85025088012

SP - 1

EP - 7

JO - BioMetals

JF - BioMetals

SN - 0966-0844

ER -