Desole, Maria Speranza and Esposito, Giovanni and Fresu, Luigia Grazia and Migheli, Rossana and Enrico, Paolo and Miele, Maddalena and De Natale, Guglielmo and Miele, Egidio (1993) 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. Neuroscience Letters, Vol. 161 (2), p. 121-123. ISSN 0304-3940. Article.
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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.
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