Neotropical Rattlesnake (Crotalus simus) Venom Pharmacokinetics in Lymph and Blood Using an Ovine Model
Edgar Neri-Castro1,2, Melisa Bénard-Valle1, Dayanira Paniagua3
1Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnologia, Universidad Nacional Autónoma de México, Av. Universidad 2001, Cuernavaca 62210, Mexico.
Toxins
|July 26, 2020
Summary
This study reveals that whole viper venom (WV) is highly bioavailable after intramuscular injection. Individual venom toxins exhibit pharmacokinetic profiles aligning with their known effects, with crotoxin rapidly targeting tissues.
Area of Science:
- Toxicology
- Pharmacokinetics
- Biochemistry
Background:
- Viper venoms contain abundant Snake Venom Metalloproteases (SVMPs), Snake Venom Serine Proteases (SVSPs), and Phospholipases (PLA2s).
- These toxins cause significant pathophysiology, but their pharmacokinetic profiles are poorly understood.
- Few studies analyze the pharmacokinetics (PK) of whole venom (WV) and its major protein families.
Purpose of the Study:
- To investigate the pathophysiology, PK profile, and differential absorption of key toxins from Neotropical Rattlesnake (Crotalus simus) venom.
- To analyze the absorption and distribution of whole venom and specific toxins in a large animal model.
- To elucidate the in vivo behavior of crotoxin, SVSPs, and SVMPs.
Main Methods:
- Pharmacokinetic analysis of whole venom (WV) and representative toxins (crotoxin, SVSPs, SVMPs) from Crotalus simus.
- Intramuscular (IM) and intravenous (IV) administration in an ovine model.
- Serum and lymph sampling to determine toxin bioavailability and distribution.
- Analysis of toxin effects including neurotoxicity, fibrinogen depletion, and hemorrhage.
Main Results:
- Whole venom (WV) demonstrated high bioavailability (86% at 60 h) after IM injection, potentially reaching 92%.
- Individual toxin PK profiles correlated with their physicochemical properties and clinical effects.
- Crotoxin was detected in lymph but not serum after IM injection, suggesting rapid tissue targeting, and was minimally detectable in serum after IV injection.
- Lymphatic absorption accounted for 1.9% of WV over 12 hours.
Conclusions:
- Neotropical rattlesnake venom exhibits high systemic bioavailability following intramuscular envenomation.
- The pharmacokinetic behavior of venom components is consistent with their known pathophysiological roles.
- Crotoxin's rapid sequestration into tissues from circulation suggests a mechanism for its potent neurotoxicity.
