Evidence for a neurotoxic activity in crude venom of the stonefish (Synanceia verrucosa).

Journal of natural toxins Pub Date : 2002-12-01
Patrick Breton, Iroudayanadin Delamanche, Janine Buée, Françoise Goudey-Perriére, Claude Perriére
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Abstract

The neurotoxic effects of the Synanceia verrucosa venom were investigated in rodents. After intracranial injection in mice (50-125 ng/g), venom induced constant symptoms such as ataxia, circling, partial or complete reversible limbs paralysis, scratching, rolling, sleep-like periods and violent clonic seizure conducing in few seconds to death. EEG alterations occurring in rat brain after intracerebroventricular injection (50-100 microg) were precised. An initial phase was characterized by short repetitive tonic seizure periods together with a significant rise of the relative power in the delta band, no significant modification of the theta II rhythm (4-7 Hz), a decreasing of energy in theta I (7-12 Hz) and 15-40 Hz bands. A second phase was characterized by a marked generalized slowing with transient drastic decreasing of the amplitude and flattening of cortical EEG (comatose state) as the main elements. Propanolol did not reverse the EEG effects of the venom except a slight decrease of the slow wave amplitude. Previous intracerebroventricular administration of a K+(ATP) blocker generally decrease the delay of death. Histopathologic examination of the brain of surviving animals did not reveal any microscopic lesions. These results suggest (1) a complex mechanism of the venom in its neuropathologic expression; (2) at the doses tested, symptoms are not related to adrenergic pathways, K+(ATP) channel opener (verrucotoxin) is not implied in the neurotoxic effect, and the effect of the venom, which not affecting the theta II rhythm, seemed not to be exerted through cholinergic pathway.

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石鱼粗毒液中神经毒性活性的证据。
本文研究了刺棘毒对啮齿动物的神经毒性作用。在小鼠颅内注射(50-125 ng/g)后,毒液引起持续的症状,如共济失调、打转、部分或完全可逆的四肢瘫痪、抓挠、滚动、嗜睡和剧烈的阵挛性发作,在几秒钟内导致死亡。测定大鼠脑室内注射50 ~ 100 μ g后的脑电图变化。初始阶段的特征是短的重复性强直性癫痫发作,δ波段的相对功率显著上升,θ II节律(4-7 Hz)无明显改变,θ I (7-12 Hz)和15-40 Hz波段的能量下降。第二阶段以脑皮层脑电图的短暂性振幅急剧下降和变平(昏迷状态)为主要特征。丙泊洛尔并没有逆转毒液对脑电图的影响,只是稍微降低了慢波振幅。先前脑室内给予K+(ATP)阻滞剂通常可减少死亡延迟。存活动物脑组织病理学检查未发现任何显微病变。这些结果表明:(1)毒的神经病理表达机制复杂;(2)在试验剂量下,症状与肾上腺素能通路无关,K+(ATP)通道打开剂(疣毒素)不含在神经毒性作用中,毒液不影响θ II节律,似乎不通过胆碱能通路发挥作用。
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