Interaction of sodium selenite on neurotoxicity induced by methylmercuric chloride
Authors
박정수
Issue Date
1990
Description
의학과/박사
Abstract
[한글]
유기수은의 신경독성에 대한 셀레늄의 보상작용은 여러가지 학설에 의해 그 기전이 보고되어 왔으나 아직까지 구체적인 세포단위에서의 기전은 잘 밝혀져 있지 않다. 신경독성을 유발시키는 유기수은의 세포내 작용기전은 유기수은의 신경세포막 침투로 presynaptic C^^a**2+ 의 투과성이 증가되고 신경세포내 C^^a**2+ 농도를 상승시키게 되며, 이로 인해 acetylcholine과 같은 신경전달물질들의 유리증가 및 저류현상을 일으켜 신경독성을 나타낸다. 반면 셀레늄은 인체구성성분인 미량금속성분으로 glutathione peroxidase의 구 성요소이며 유기수은으로 인한 지질과산화를 억제시키고 세포막구조를 안정화시키는 작용을 지니고 있다. 본 연구에서는 유기수은의 신경독성에 대한 셀레늄의 보상효과 기전의 일부를 규명하고자 유기수은으로 인한 세포내 C^^a**2+ 농도 상승에 셀레늄이 어떠한 영
향을 미치는가 관찰하여 보고자 하였다.
유기수은으로는 CH^^3 H^^g Cl을 셀레늄은 Na^^2 S^^e O^^3 를 선정하여 흰쥐를 대상으로한 생체내 실험과 synaptosome을 이용한 실험관내 실험을 병행하여 실시하였다. 체중 200g 내외의 수컷 흰쥐 75마리를 대상으로 CH^^3 H^^g Cl(3mg/kg)과 Na^^2 S^^e O^^3 (5mg
이상의 실험결과를 종합하여 보면 특정용량의 N^^a^^2 S^^e O^^3는 CH^^3 H^^g Cl 투여로 인한 세포내 C^^a**2+ 의 증가를 저하시키므로 C^^3 H^^g Cl의 신경독성에 보상효과를 지니고 있음을 알 수 있었다.
[영문]
This study was conducted to investigate the mechanism of protective effect by sodium selenite in methylmercuric chloride neurotoxicity, increasing intracellular C^^a**2+ concentration of the neuron.
Methylmercuric chloride of 3mg/kg of body weight was administered simultaneously with sodium selenite of 5mg/kg and pretreatment of sodium selenite via intraperitoneal injection to rat.
Also, Effects of methylmercuric chloride (25μM, 50μM, 100μM) and sodium selenite (200μM) on free intrasynaptosomal C^^a**2+ concentration were studied using the fluorescent C^^a**2+ indicator fura-2 in vitro.
After the treatment, at 6, 24, and 48 hours later, mercury in the cerebral cortex, liver and kidney tissues, succinic dehydrogenase activities, andenosine-5'-triphosphate concentration, acetylcholinesterase activities, and
intracellular C^^a**2+ concentration in the cerebral cortex were determined in vivo.
Cerebral synaptosomes of rats were incubated with methylmercuric chloride and sodium selenite in Hepes buffer for 10 minutes and free intrasynaptosomal C^^a**2+ concentration were measured with fura-2 in vitro.
The results were summarized as follows
1.The combined administration of CH^^3 H^^g Cl and N^^a^^2 S^^e O^^3 and pretreatment of N^^a^^2 S^^e O^^3 according to time significantly more increased in the cerebral cortex and decreased in the liver, kidney mercury concentrations compared to the administration of CH^^3 H^^g Cl only.
2. The combined administration of CH^^3 H^^g Cl and N^^a^^2 S^^e O^^3 and pretreatment of N^^a^^2 S^^e O^^3 increased more succinic dehydrogenase and acetylcholinesterase activities compared to the administration of CH^^3 H^^g Cl only. Particularly pretreatment of N^^a^^ S^^e O^^3 increased significantly more compared to the administration of CH^^3 H^^g Cl only. The concentration of adenosine-5'-triphosphate in N^^a^^2 S^^e O^^3 treatment groups revealed a favourable effect compared to administration of CH^^3 H^^g Cl only.
3. Intracellular C^^a^^2+ concentration in administration of CH^^3 H^^g Cl only was increased significantly more than control group in all test hours but was increased significantly more at 48 hours only after treatment in combined administration of CH^^3 H^^g Cl and N^^a^^2 S^^e O^^3 and pretreatment of N^^a^^2
S^^e O^^3. The combined administration of CH^^3 H^^g Cl and N^^a^^2 S^^e O^^3 and pretreatment of N^^a^^2 S^^e O^^3 according to time interval more decreased significantly intracellular C^^a**2+ concentration compared to the administration of CH^^3 H^^g Cl only.
4. Free intrasynaptosomal C^^a**2+ concentration in the combined administration of CH^^3 H^^g Cl and N^^a^^2 S^^e O^^3 was decreased (24%-40%) significantly more than the administration of CH^^3 H^^g Cl only.
From the above results, the specific dosage of N^^a^^2 S^^e O^^3 decreased incrementally of intracellular C^^a**2+ concentration induced by administration of CH^^3 H^^g Cl. These findings suggest the protective mechanism of N^^a^^ S^^e O^^3