TY - JOUR
T1 - Neotropical rattlesnake (Crotalus simus) venom pharmacokinetics in lymph and blood using an ovine model
AU - Neri-Castro, Edgar
AU - Bénard-Valle, Melisa
AU - Paniagua, Dayanira
AU - Boyer, Leslie V.
AU - Possani, Lourival D.
AU - López-Casillas, Fernando
AU - Olvera, Alejandro
AU - Romero, Camilo
AU - Zamudio, Fernando
AU - Alagón, Alejandro
N1 - Funding Information:
Funding: This research was funded by UNAM grant number PAPIIT-DGAPA IN207218 and CONACyT grant number Venenos y antivenenos 303045, Fondo Institucional de Fomento Regional para el Desarrollo Científico, Tecnológico y de Innovación (FORDECYT), Mexico.
Funding Information:
Acknowledgments: Edgar Neri Castro is a doctoral student from the Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México (UNAM) and a scholarship recipient from Consejo Nacional de Ciencia y Tecnología (CONACyT) with registration number 254145. We thank María Fernanda Aguas, Oscar Aguayo, Oscar Jiménez, Felipe Olvera and Roberto Ponce for their help in the experiments with the animals, and Hilda Vázquez for her support in administration of resources for the project. The authors thank José María Gutierrez for reviewing the manuscript. The authors thank Andrés Baltazar Alagón Cano, Jesús Pulido Hernández and Jesús Adalberto Pulido Carballo for the husbandry of horses. We thank Rubén Carbajal and Jason M. Jones for the taxonomic help provided during this project. We thank Roberto Olivares Hernández for his support and discussions during the project.
Publisher Copyright:
© 2020 by the authors.
PY - 2020/7
Y1 - 2020/7
N2 - The most abundant protein families in viper venoms are Snake Venom Metalloproteases (SVMPs), Snake Venom Serine Proteases (SVSPs) and Phospholipases (PLA2s). These are primarily responsible for the pathophysiology caused by the bite of pit-vipers; however, there are few studies that analyze the pharmacokinetics (PK) of whole venom (WV) and its protein families. We studied the pathophysiology, PK profile and differential absorption of representative toxins from venom of Neotropical Rattlesnake (Crotalus simus) in a large animal model (ovine). Toxins studied included crotoxin (the main lethal component), which causes moderate to severe neurotoxicity; SVSPs, which deplete fibrinogen; and SVMPs, which cause local tissue damage and local and systemic hemorrhage. We found that Whole Venom (WV) was highly bioavailable (86%) 60 h following intramuscular (IM) injection, and extrapolation suggests that bioavailability may be as high as 92%. PK profiles of individual toxins were consistent with their physicochemical properties and expected clinical effects. Lymph cannulated animals absorbed 1.9% of WV through lymph during the first 12 h. Crotoxin was minimally detectable in serum after intravenous (IV) injection; however, following IM injection it was detected in lymph but not in blood. This suggests that crotoxin is quickly released from the blood toward its tissue targets.
AB - The most abundant protein families in viper venoms are Snake Venom Metalloproteases (SVMPs), Snake Venom Serine Proteases (SVSPs) and Phospholipases (PLA2s). These are primarily responsible for the pathophysiology caused by the bite of pit-vipers; however, there are few studies that analyze the pharmacokinetics (PK) of whole venom (WV) and its protein families. We studied the pathophysiology, PK profile and differential absorption of representative toxins from venom of Neotropical Rattlesnake (Crotalus simus) in a large animal model (ovine). Toxins studied included crotoxin (the main lethal component), which causes moderate to severe neurotoxicity; SVSPs, which deplete fibrinogen; and SVMPs, which cause local tissue damage and local and systemic hemorrhage. We found that Whole Venom (WV) was highly bioavailable (86%) 60 h following intramuscular (IM) injection, and extrapolation suggests that bioavailability may be as high as 92%. PK profiles of individual toxins were consistent with their physicochemical properties and expected clinical effects. Lymph cannulated animals absorbed 1.9% of WV through lymph during the first 12 h. Crotoxin was minimally detectable in serum after intravenous (IV) injection; however, following IM injection it was detected in lymph but not in blood. This suggests that crotoxin is quickly released from the blood toward its tissue targets.
KW - Crotalus simus venom
KW - Crotoxin
KW - Differential absorption of venom protein families
KW - Lymphatic system
KW - Pharmacokinetics of venom
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U2 - 10.3390/toxins12070455
DO - 10.3390/toxins12070455
M3 - Article
C2 - 32708875
AN - SCOPUS:85088679741
SN - 2072-6651
VL - 12
JO - Toxins
JF - Toxins
IS - 7
M1 - 455
ER -