Guidine Patrícia Alves Maia, Moraes-Santos Tasso, Massensini André Ricardo, Moraes Márcio Flávio Dutra
Núcleo de Neurociências (NNC), Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627 Pampulha, 31270 901 Belo Horizonte, Minas Gerais, Brazil.
Neurotoxicology. 2008 Jan;29(1):136-42. doi: 10.1016/j.neuro.2007.10.004. Epub 2007 Oct 13.
The scorpion envenoming syndrome is a serious public health matter in Brazil. Previous results from our laboratory suggest that the effects of scorpion toxins on the central nervous system play a major role on the lethality induced by scorpion envenoming. The objective of this work is to evaluate carbamazepine (CBZ) as a potential therapeutic agent against tityustoxin (TsTX) envenomation. The choice of i.c.v. toxin injection assures that TsTX is readily available in the parenchyma, configuring a worst case scenario for protecting the CNS afflicted by envenomation. Adult Wistar rats were submitted to surgery for guide cannulae (lateral ventricle) and electrodes (EEG-parietal cortices and ECG-thoracic leads) implantation. Animals (n=25) were treated with i.p. injections of either vehicle or CBZ 90 min before injected i.c.v. with a fixed volume of either saline or TsTX: vehicle treated/TsTX injected (1.74 microg, i.c.v.; n=4), CBZ treated (50mg/kg, i.p.)/TsTX injected (n=12); CBZ treated/saline injected (n=5); and vehicle treated/saline injected (n=4). Video EEG/ECG was recorded until death or for a maximum period of 90 min. Lungs were excised and weighed to evaluate edema. The results showed that 10 out of 12 CBZ treated rats survived to TsTX i.c.v. microinjection. CBZ significantly decreased cardiac arrhythmias and pulmonary edema in rats injected with TsTX. Furthermore, CBZ also significantly increased the latency for the first cortical epileptiform discharge. The known effect of CBZ reducing neuronal excitability most likely protected the neural substrates targeted by TsTX. CBZ was efficient in attenuating envenoming symptoms after the i.c.v. inoculation of the TsTX in rats. Thus, CBZ can be proposed as a therapeutic coadjuvant in the treatment of scorpion poisoning.
在巴西，蝎子蜇伤综合征是一个严重的公共卫生问题。我们实验室之前的研究结果表明，蝎子毒素对中枢神经系统的作用在蝎子蜇伤所致的致死率中起主要作用。本研究的目的是评估卡马西平（CBZ）作为一种潜在的抗替尤斯毒素（TsTX）蜇伤治疗药物的效果。采用脑室内注射毒素的方式可确保TsTX在脑实质中迅速起效，这为保护受蜇伤影响的中枢神经系统设定了最不利的情况。成年Wistar大鼠接受手术植入引导套管（侧脑室）和电极（脑电图 - 顶叶皮质和心电图 - 胸导联）。在脑室内注射固定体积的生理盐水或TsTX前90分钟，对动物（n = 25）进行腹腔注射溶剂或CBZ：溶剂处理/注射TsTX（1.74微克，脑室内注射；n = 4），CBZ处理（50毫克/千克，腹腔注射）/注射TsTX（n = 12）；CBZ处理/注射生理盐水（n = 5）；溶剂处理/注射生理盐水（n = 4）。记录视频脑电图/心电图直至死亡或最长记录90分钟。切除肺脏并称重以评估水肿情况。结果显示，12只接受CBZ处理的大鼠中有10只在脑室内微量注射TsTX后存活下来。CBZ显著降低了注射TsTX大鼠的心律失常和肺水肿。此外，CBZ还显著延长了首次皮质癫痫样放电的潜伏期。CBZ降低神经元兴奋性的已知作用很可能保护了TsTX靶向的神经底物。在大鼠脑室内接种TsTX后，CBZ能有效减轻蜇伤症状。因此，可将CBZ作为蝎子中毒治疗的辅助治疗药物。
