Fornstedt B, Carlsson A
Department of Pharmacology, University of Göteborg, Sweden.
J Neurochem. 1991 Feb;56(2):407-14. doi: 10.1111/j.1471-4159.1991.tb08166.x.
Being a catechol, dopamine (DA) is easily autoxidized in solution to a semiquinone and then further to a quinone. These quinones and by-products, as reduced forms of oxygen, are all cytotoxic. By quantifying quinone metabolites, such as 5-S-cysteinyl adducts of DA, 3,4-dihydroxyphenylalanine (DOPA), and 3,4-dihydroxyphenylacetic acid (DOPAC), an indirect measure of catechol autoxidation is available. Ascorbic acid (AA) has an important role as an antioxidant in the organism. A group of guinea pigs (Dunkin-Hartley) received an AA-free diet for 37 days, whereas a control group was fed an AA-containing diet (1,400 mg/kg of pellets). To one group of AA-deprived animals a single dose of AA (500 mg/kg, i.p.) was administered 2 h before death, whereas another group received two doses 9 and 24 h before death. The striatal levels of 5-S-cysteinyl adducts, DA, noradrenaline, and DOPAC and the cerebellar and the limbic levels of AA were determined. A significant increase in 5-S-cysteinyl-DA content was found in the striatum of AA-deficient animals (143 +/- 12% of control values). A further increase was found 2 h after an AA injection (177 +/- 16% of control values), which was significant compared with both controls and AA-deficient animals. An elevation in 5-S-cysteinyl-DA content was still observed following two AA injections during a 24-h period (153 +/- 7% of control values). The 5-S-cysteinyl-DOPAC content increased significantly (134 +/- 14% of control values) in the AA-deficient animals given AA acutely (2 h), both compared with controls and with the AA-deficient group.(ABSTRACT TRUNCATED AT 250 WORDS)
作为一种儿茶酚,多巴胺(DA)在溶液中很容易自动氧化为半醌,然后进一步氧化为醌。这些醌及其副产物作为氧的还原形式,都具有细胞毒性。通过定量醌代谢产物,如DA、3,4-二羟基苯丙氨酸(DOPA)和3,4-二羟基苯乙酸(DOPAC)的5-S-半胱氨酰加合物,可以间接测量儿茶酚的自动氧化。抗坏血酸(AA)在生物体中作为抗氧化剂发挥着重要作用。一组豚鼠(Dunkin-Hartley)接受了37天的无AA饮食,而对照组则喂食含AA的饮食(每千克颗粒1400毫克)。对一组缺乏AA的动物在死亡前2小时给予单剂量AA(500毫克/千克,腹腔注射),而另一组在死亡前9小时和24小时接受两剂AA。测定了纹状体中5-S-半胱氨酰加合物、DA、去甲肾上腺素和DOPAC的水平以及小脑和边缘系统中AA的水平。在缺乏AA的动物纹状体中发现5-S-半胱氨酰-DA含量显著增加(为对照值的143±12%)。注射AA后2小时进一步增加(为对照值的177±16%),与对照组和缺乏AA的动物相比均有显著差异。在24小时内注射两剂AA后,仍观察到5-S-半胱氨酰-DA含量升高(为对照值的153±7%)。与对照组和缺乏AA的组相比,急性给予AA(2小时)的缺乏AA的动物中5-S-半胱氨酰-DOPAC含量显著增加(为对照值的134±14%)。(摘要截断于250字)