Efficacy of Trypsin in Treating Coral Snake Envenomation in the Porcine Model

Abstract

Antivenom is the definitive treatment for venomous snakebites. Alternative treatments warrant investigation because antivenom is sometimes unavailable, expensive, and can have deleterious side effects. This study assesses the efficacy of trypsin to treat coral snake envenomation in an in vivo porcine model. A randomized, blinded study was conducted. Subjects were 13 pigs injected subcutaneously with 1 mL of eastern coral snake venom (10 mg/mL) in the right distal hind limb. After 1 min, subjects were randomized to have the envenomation site injected with either 1 mL of saline or 1 mL of trypsin (100 mg/mL) by a blinded investigator. Clinical endpoint was survival for 72 h or respiratory depression defined as respiratory rate <15 breaths per minute, falling pulse oximetry, or agonal respirations. Fisher's exact t test was used for between group comparisons. Average time to toxicity for the saline control was 263 min (191-305 min). The development of respiratory depression occurred more frequently in control pigs than treated pigs (p = 0.009). Four of the six pigs that received trypsin survived to the end of the 3-day study. No control pigs survived. Two of the trypsin treatment pigs died with times to toxicity of 718 and 971 min. Survival to 12 and 24 h was significantly greater in the trypsin treatment group (p = 0.002, p = 0.009, respectively). Local injection of trypsin, a proteolytic enzyme, at the site of envenomation decreased the toxicity of eastern coral snake venom and increased survival significantly. Further investigation is required before these results can be extended to human snakebites.

Delayed LY333013 (Oral) and LY315920 (Intravenous) Reverse Severe Neurotoxicity and Rescue Juvenile Pigs from Lethal Doses of Micrurus fulvius (Eastern Coral Snake) Venom

“…The results cannot yet be generalized to the neutralization of a broad range of snake venom sPLA2s and associated pathology but the toxin-specific approach is being increasingly investigated as a treatment for snakebite both alone and in conjunction with antivenom [ 7 , 9 , 10 , 23 , 24 , 26 ]. This was advantageous in guiding these experiments and to allow some reasonable comparison of results [ 30 , 31 , 32 , 33 ]. The domestic porcine model may be a stringent model to study gastrointestinal transit and absorption of drugs because gastric emptying in Sus domesticus is amongst the slowest of mammals and may have provided a more robust challenge to the oral drug, LY333013, than using minipigs bred for their accelerated gastrointestinal clearance [ 38 ].…”

“…M. fulvius venom was chosen for porcine testing because of its clinical relevance in North America, the fact that there is a scarcity of available antivenoms, and because its main toxic activities depend on the action of PLA2s [ 27 ]. In addition, M. fulvius venom proved to have high reliability in preliminary porcine lethality tests, reducing the likelihood of unnecessary animal use [ 30 , 31 , 32 , 33 ].…”

Asperosaponin VI facilitates the regeneration of skeletal muscle injury by suppressing GSK‐3β‐mediated cell apoptosis

“…Male C57BL/6 mice (10–12 weeks old, 23 ± 2 g) were purchased from SiPeiFu (Beijing) Biotechnology Co. Ltd., then fed in an specific pathogen free facility with a constant a 12‐h light/dark cycle, and provided with food and water ad libitum. Following isoflurane anesthesia, 30 μL of 10 μM CTX dissolved in PBS was intramuscularly injected into the right tibialis anterior (TA) muscle to induce injury and trypsin was injected at the same location mice were randomly divided into five groups: control, CTX‐induced muscle injury, 1500 U kg −1 trypsin 20 (Trypsin), 10 mg kg −1 day −1 ASA VI (A10) and 20 mg kg −1 day −1 ASA VI (A20), with six mice per group at each time point. ASA VI was administered by gavage.…”

First Aid and Pre-Hospital Management of Venomous Snakebites

“…The proposed mechanism of action is to digest protein venoms. A randomized, blinded study in anesthetized pigs was conducted [ 34 ]. One minute after injection in a distal hind limb of 10 mg of eastern coral snake venom ( Micrurus fulvius fulvius ) dissolved in 1 mL of water, subjects were randomized to receive either 1 mL of saline or 1 mL of trypsin (100 mg/mL) at the envenomation site by a blinded investigator.…”