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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

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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DOI: 10.1016/0304-3940(93)90274-O

Abstract

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.

Item Type:Article
ID Code:4378
Status:Published
Refereed:Yes
Uncontrolled Keywords:MPTP, uric acid, antioxidant system, striatal synaptosome, rat
Subjects:Area 05 - Scienze biologiche > BIO/14 Farmacologia
Divisions:001 Università di Sassari > 01 Dipartimenti > Scienze biomediche
001 Università di Sassari > 01 Dipartimenti > Neuroscienze, scienze materno infantili
Publisher:Elsevier Science Ireland
ISSN:0304-3940
Copyright Holders:© 1993 Published by Elsevier Ireland Ltd.
Deposited On:26 Aug 2010 13:52

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