Study of crotoxin on the induction of paralysis in extraocular muscle in animal model

Abstract

Purpose: Crotoxin is the major toxin of the venom of the South American rattlesnake Crotalus durissus terrificus, capable of causing a blockade of the neurotransmitters at the neuromuscular junction. The objective of this study was to appraise the action and effectiveness of the crotoxin induced paralysis of the extraocular muscle and to compare its effects with the botulinum toxin type A (BT-A). Methods: The crotoxin, with LD50 of 1.5 μg, was injected into the superior rectus muscle in ten New Zealand rabbits. The concentration variance was 0.015 up to 150 μg. Two rabbits received 2 units of botulinum toxin type A for comparative analysis. The evaluation of the paralysis was performed using serial electromyography. After the functional recovery of the muscles, which occurred after two months, six rabbits were sacrificed for anatomopathology study. Results:The animals did not show any evidence of systemic toxicity. Transitory ptosis was observed in almost every animal and remained up to fourteen days. These toxins caused immediate blockade of the electrical potentials. The recovery was gradual in the average of one month with regeneration signs evident on the electromyography. The paralysis effect of the crotoxin on the muscle was proportional to its concentration. The changes with 1.5 μg crotoxin were similar to those produced by the botulinum toxin type A. The histopathology findings were localized to the site of the injection. No signs of muscle fiber's necrosis were seen in any sample. The alterations induced by crotoxin were also proportional to the concentration and similar to botulinum toxin type A in concentration of 1.5 μg. Conclusion: Crotoxin was able to induce transitory paralysis of the superior rectus muscle. This effect was characterized by reduction of action potentials and non-specific signs of fibrillation. Crotoxin, in concentration of 1.5 μg was able to induce similar effects as botulinum toxin type A. Keywords

Crotoxin-Induced Mice Lung Impairment: Role of Nicotinic Acetylcholine Receptors and COX-Derived Prostanoids

“…To investigate how CTX affects respiratory physiology, we selected a dose that causes significant intoxication by evaluating some biological alterations, based on previous findings. CTX-induced locomotor alterations are associated with neuromuscular disturbances caused by neuromuscular blockade [16,17,32,33] and myotoxicity [20,34]. We found that subcutaneous injection of CTX at a dose of 300 µg/Kg significantly decreased mice exploratory activity at the open field test and increased serum CK, which indicate locomotor impairment and systemic myotoxicity.…”

Neste fascículo dos ABO

“…The importance of this paper lies in the fact that, although almost 10% of people with bilateral blindness live in the Americas, methodologically appropriate, ophthalmic population-based studies are infrequent in Latin America (7) . Also in this issue, it has been described, for the first time, the effects of a neurotoxin isolated from the venom of a South American rattlesnake in the external ocular muscles (8) . The crotoxin was applied to the superior rectus muscle of rabbits and compared with botulinum toxin type A.…”