CORRELATION BETWEEN 1-METHYL-4-PHENYLPYRIDINIUM ION (MPP+) LEVELS, ASCORBIC-ACID OXIDATION AND GLUTATHIONE LEVELS IN THE STRIATAL SYNAPTOSOMES OF THE 1-METHYL-4-PHENYL-1,2,3-6-TETRAHYDROPYRIDINE (MPTP)-TREATED RAT
CORRELATION BETWEEN 1-METHYL-4-PHENYLPYRIDINIUM ION (MPP+) LEVELS, ASCORBIC-ACID OXIDATION AND GLUTATHIONE LEVELS IN THE STRIATAL SYNAPTOSOMES OF THE 1-METHYL-4-PHENYL-1,2,3-6-TETRAHYDROPYRIDINE (MPTP)-TREATED RAT
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DOI：
10.1016/0304-3940(93)90274-o
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发表时间：
1993-10-29
影响因子：
2.5
通讯作者：
MIELE, E
中科院分区：
文献类型：
--
作者：
DESOLE, MS;ESPOSITO, G;MIELE, E
用高效液相色谱法测定6月龄雄性Wistar大鼠单次注射MPTP 35 mg/kg后，纹状体突触体内多巴胺(DA)、二羟基苯乙酸(DOPAC)、抗坏血酸(AA)、脱氢抗坏血酸(DHAA)、尿酸、谷胱甘肽(GSH)和1-甲基-4-苯基吡啶离子(MPP+)的含量。1-甲基-4-苯基-1，2，3-6-四氢吡啶(MPTP)在15min~10h内可致大鼠死亡，死亡率为32.5%。MPTP可显著升高DHAA和尿酸水平，降低DOPAC和GSH水平。突触体内MPP+与DOPAC(r=-0.601，P<0.002)、GSH(r=-0.496，P<0.01)呈负相关，与尿酸(r=+0.627，P<0.001)呈正相关，后者与DHAA(r=+0.418，P<0.05)、GSH(r=-0.357，P=0.07)呈负相关。综上所述，内源性抗氧化系统的反应(AA氧化增加，GSH水平降低)与MPTP诱导的尿酸水平升高有很好的相关性，并为MPTP神经毒性的机制提供了进一步的证据，该机制涉及黄嘌呤氧化酶产生的氧化应激。
In 6-month-old male Wistar rats, levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), ascorbic acid (AA), dehydroascorbic acid (DHAA), uric acid, glutathione (GSH) and 1-methyl-4-phenylpyridinium ion (MPP+) were determined by HPLC in the crude striatal synaptosomal fraction after single injections of MPTP 35 mg/kg i.p. 1-Methyl-4-phenyl-1,2,3-6-tetrahydropyridine (MPTP) induced a 32.5% death rate within 15 min to 10 h. Groups of surviving rats were sacrificed 1, 3, 8 and 24 h after MPTP. MPTP significantly increased levels of DHAA and uric acid and decreased levels of DOPAC and GSH. Individual synaptosomal levels of MPP+ were correlated inversely with DOPAC (r = -0.601, P < 0.002) and GSH levels (r = -0.496, P < 0.02) and directly with levels of uric acid (r = +0.627, P < 0.001); these latter, in turn, were correlated with DHAA (r = +0.418, P < 0.05) and GSH levels (r = -0.357, P = 0.07). In conclusion, the response of the endogenous antioxidant system (increase in AA oxidation, decrease in GSH levels) correlates well with the MPTP-induced increase in uric acid levels and provides further evidence for a mechanism of MPTP neurotoxicity involving oxidative stress produced by xanthine oxidase.