Leśkiewicz M, Budziszewska B, Jaworska-Feil L, Lasoń W
Department of Endocrinology, Polish Academy of Sciences, Kraków, Poland.
Pol J Pharmacol. 1997 Nov-Dec;49(6):411-7.
In the present study we examined effects of some neurosteroids on the kainate-induced seizures, lethality and neurotoxicity in mice. We found that 5 alpha-pregnan-3 alpha-ol-20-one (allopregnanolone; 10 and 20 mg/kg) markedly elevated CD50 for kainate-induced convulsions, whereas 5 beta-pregnan-3 alpha-ol-20-one, 5 alpha-pregnan-3 alpha-ol-11,20-dione, 5 alpha-androstan-3 alpha-ol-17-one, dehydroepiandrosterone sulfate, pregnenolone sulfate and aminosteroid (U-107) were ineffective in that test. Furthermore, 5 alpha-pregnan-3 alpha-ol-20-one (5-20 mg/kg), 5 beta-pregnan-3 alpha-ol-20-one (20 mg/kg) and 5 alpha-androstan-3 alpha-ol 17-one (10 and 20 mg/kg) decreased, while dehydroepiandrosterone sulfate (25 and 50 mg/kg) and pregnenolone sulfate (25 mg/kg) elevated the kainate-induced lethality in mice. A histological analysis showed that kainate caused a dose-dependent neuronal loss of CA1 and CA3 hippocampal fields. Of the neurosteroids tested, only allopregnanolone attenuated the kainate-induced neurotoxicity. The above data indicate that neurosteroids exert moderate effects on seizures and neurotoxic effects of kainate. On the other hand, neurosteroids with a GABAA receptor agonistic or antagonistic activity decrease or increase, respectively, the kainate-evoked lethality.
在本研究中，我们检测了某些神经甾体对红藻氨酸盐诱导的小鼠癫痫发作、致死率和神经毒性的影响。我们发现，5α-孕烷-3α-醇-20-酮（别孕烯醇酮；10和20mg/kg）显著提高了红藻氨酸盐诱导惊厥的半数惊厥剂量（CD50），而5β-孕烷-3α-醇-20-酮、5α-孕烷-3α-醇-11,20-二酮、5α-雄甾烷-3α-醇-17-酮、硫酸脱氢表雄酮、硫酸孕烯醇酮和氨基甾体（U-107）在该试验中无效。此外，5α-孕烷-3α-醇-20-酮（5-20mg/kg）、5β-孕烷-3α-醇-20-酮（20mg/kg）和5α-雄甾烷-3α-醇17-酮（10和20mg/kg）降低了红藻氨酸盐诱导的小鼠致死率，而硫酸脱氢表雄酮（25和50mg/kg）和硫酸孕烯醇酮（25mg/kg）提高了该致死率。组织学分析表明，红藻氨酸盐导致海马CA1和CA3区剂量依赖性神经元丢失。在所检测的神经甾体中，只有别孕烯醇酮减轻了红藻氨酸盐诱导的神经毒性。上述数据表明，神经甾体对红藻氨酸盐的癫痫发作和神经毒性有适度影响。另一方面，具有GABAA受体激动或拮抗活性的神经甾体分别降低或提高了红藻氨酸盐诱发的致死率。
