THESIS: C. M. V. de Souza submitted this thesis for the degree of Master in Experimental Pathology publicly examined at the Department of Pathology, Centro de Ciências Médicas, Universidade Federal Fluminense UFF - Niterói, Rio de Janeiro, Brazil in 1999.
Advisor: Prof. Dr. Miguel Benito Farah
ABSTRACT. An experimental model was developed to study convulsions induced in mice by the venom from the yellow scorpion Tityus serrulatus Lutz & Mello. The intraperitoneal (IP) administration of Tityus serrulatus crude venom (1.5 mg/kg) induced a repeatable scorpion envenoming syndrome in mice with manifestations similar to those already described in severe human envenoming. In this experimental model, the effects of anticonvulsant drugs (Diazepam, Phenytoin, and Phenobarbital) and specific antivenom on convulsions (2 hours of continuous observation) and lethality (2, 24, and 48 hours) were analyzed. Intraperitoneal administration of venom (1.5 mg/kg) induced seizures in a large number of mice treated with saline (87.8% ± 3.9%, n=116). The venom also induced a high level of lethality in the same group after 24 hours (74.2% ± 1.1%, n=116). There was no further change in lethality 48 hours after venom administration. Only pre-treatment with the highest dose of antivenom (12.5 ml/kg IP) protected against venom-induced convulsions. However, the latency time for those animals developing convulsions was reduced. None of the three doses of antivenom used (0.5, 2.0, 12.5 ml/kg IP) were able to reduce the total number of convulsions. The 24-hour lethality induced by the venom was reduced by pre-treatment with antivenom (2.0 and 12.5 ml/kg IP). Pre-treatment with 0.5 ml/kg IP of antivenom delayed venom-induced lethality 2 hours after venom injection, but the protective effect was not observed when the lethality was recorded at 24 hours. Phenytoin (3.5, 10.0, and 30.0 mg/kg IP) protected a significant number of mice against seizures. Pre-treatment with Phenytoin did not change the latency to the first convulsion or the number of convulsions those animals developed. Phenytoin (3.5 and 10.0 mg/kg IP) was also able to protect against 24-hour lethality. Pre-treatment with Diazepam (0.3, 1.0, 3.0, and 10.0 mg/kg IP) did not change the number of animals that developed seizures when compared with the control mice. The highest doses used (3.0 and 10.0 mg/kg IP) increased the time to the first seizure. The number of convulsions in the 2-hour period of continuous observation was reduced after pre-treatment with diazepam (3.0 and 10.0 mg/kg IP). Pre-treatment with Diazepam did not change the lethality induced by Tityus serrulatus venom. Phenobarbital (3.5, 10.0, and 30.0 mg/kg IP) did not protect against convulsions or change the latency to the first convulsion. Phenobarbital 30.0 mg/kg IP increased the number of venom-induced convulsions. Phenobarbital did not protect against the lethality induced by the venom in this experimental model. In conclusion: 1) The experimental model developed is suitable to investigate seizures induced by Tityus serrulatus venom. 2) Specific antivenom was not effective in protecting against seizures induced by Tityus serrulatus venom, since protection against seizures was only achieved with the dose that reduced the time to the first seizure. Our results also suggest that high doses of antivenom are required to protect against lethality in severe scorpion envenoming in mice. 3) The protective effects of Phenytoin probably involve the antagonist action of Phenytoin against scorpion venom on sodium channels. Further investigations are necessary to establish whether this drug is a useful tool in the clinical approach of human envenoming induced by Tityus serrulatus. 4) The anticonvulsant pathway showed by Diazepam suggests its interaction with gabaergic mechanisms involved in convulsion control. 5) Phenobarbital is not a suitable protection against seizures induced by Tityus serrulatus venom.
CORRESPONDENCE TO:
C. M. V. de SOUZA - Divisão de Animais Peçonhentos, Instituto Vital Brazil, Caixa Postal 100.028, CEP 24230-340, Niterói, RJ, Brasil.
Publication Dates
-
Publication in this collection
25 Feb 2000 -
Date of issue
2000
