Semi-chronic increase in striatal level of 3,4-dihydroxyphenylacetaldehyde does not result in alteration of nigrostriatal dopaminergic neurones
Semi-chronic increase in striatal level of 3,4-dihydroxyphenylacetaldehyde does not result in alteration of nigrostriatal dopaminergic neurones
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DOI：
10.1002/jnr.10880
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发表时间：
2004-02-01
影响因子：
4.2
通讯作者：
Costentin, J
中科院分区：
文献类型：
--
作者：
Legros, H;Janin, F;Costentin, J
本研究旨在评价3，4-二羟基苯乙醛（DOPAL）的潜在体内毒性，DOPAL是一种通过单胺氧化酶（MAO）由多巴胺形成的醛，主要通过脑醛脱氢酶（ALDH）氧化为3，4-二羟基苯乙酸（DOPAC）。在这项研究中，雄性Sprague-Dawley大鼠用左旋多巴（L-dopa）-苄丝肼和双硫仑治疗，左旋多巴（L-dopa）-苄丝肼可增加MAO产生的DOPAL，双硫仑是ALDH的不可逆抑制剂，可减少DOPAL形成DOPAC。急性全身性腹膜内（i. p.）注射100 mg/kg双硫仑和L-多巴-苄丝肼（100 mg/kg + 25 mg/kg，24小时后）显著增加DOPAL纹状体水平。用双硫仑（100 mg/kg i. p.，每2天一次）和L-多巴-苄丝肼（100 mg/kg + 25 mg/kg，每天两次）不影响用于评估黑质纹状体多巴胺能神经元完整性的任一指标（即，多巴胺的纹状体含量和与纹状体膜上的囊泡单胺转运体的结合）。这些结果没有证明多巴酚丁胺的任何有害作用，并反对左旋多巴治疗的毒性。(C)2004 Wiley-Liss，Inc.
This work was carried out to evaluate the potential in vivo toxicity of 3,4-dihydroxyphenylacetaldehyde (DOPAL), an aldehyde formed from dopamine by monoamine oxidase (MAO) that is oxidised mainly to 3,4-dihydroxyphenylacetic acid (DOPAC) by brain aldehyde dehydrogenases (ALDH). In this study, male Sprague-Dawley rats were treated with levodopa (L-dopa)-benserazide, which increases DOPAL production by MAO, and disulfiram, an irreversible inhibitor of ALDH, which reduces the formation of DOPAC from DOPAL. An acute systemic intraperitoneal (i.p.) injection of 100 mg/kg disulfiram and L-dopa-benserazide (100 mg/kg + 25 mg/kg, 24 hr later) significantly increased DOPAL striatal level. A 30-day treatment with disulfiram (100 mg/kg i.p., once every 2 days) and L-dopa-benserazide (100 mg/kg + 25 mg/kg, two times/day) did not affect either indexes used to assess integrity of the nigrostriatal dopaminergic neurones (i.e., the striatal content in dopamine and binding to the vesicular monoamine transporter on striatal membranes). These results do not evidence any deleterious effect of DOPAL and argue against toxicity Of L-dopa therapy. (C) 2004 Wiley-Liss, Inc.