Neotropical rattlesnake (Crotalus simus) venom pharmacokinetics in lymph and blood using an ovine model

Edgar Neri-Castro, Melisa Bénard-Valle, Dayanira Paniagua, Leslie V. Boyer, Lourival D. Possani, Fernando López-Casillas, Alejandro Olvera, Camilo Romero, Fernando Zamudio, Alejandro Alagón

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number455
JournalToxins
Volume12
Issue number7
DOIs
StatePublished - Jul 2020

Keywords

  • Crotalus simus venom
  • Crotoxin
  • Differential absorption of venom protein families
  • Lymphatic system
  • Pharmacokinetics of venom

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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