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Human & Experimental Toxicology
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*1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE
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Effect of intraventricular injection of 1-methyl-4-phenylpyridinium: protection by acetyl-L-carnitine

V. Steffen

Departamento de Bioquímica, Bromatologia y Toxicologia, Facultad de Farmacia, Universidad de Sevilla, C/ Prof García Gonzalez, Sevilla 41012, Spain

M. Santiago

Departamento de Bioquímica, Bromatologia y Toxicologia, Facultad de Farmacia, Universidad de Sevilla, C/ Prof García Gonzalez, Sevilla 41012, Spain

CP de la Cruz

Departamento de Bioquímica, Bromatologia y Toxicologia, Facultad de Farmacia, Universidad de Sevilla, C/ Prof García Gonzalez, Sevilla 41012, Spain

E. Revilla

Departamento de Bioquímica, Bromatologia y Toxicologia, Facultad de Farmacia, Universidad de Sevilla, C/ Prof García Gonzalez, Sevilla 41012, Spain

A. Machado

Departamento de Bioquímica, Bromatologia y Toxicologia, Facultad de Farmacia, Universidad de Sevilla, C/ Prof García Gonzalez, Sevilla 41012, Spain

J. Cano

Departamento de Bioquímica, Bromatologia y Toxicologia, Facultad de Farmacia, Universidad de Sevilla, C/ Prof García Gonzalez, Sevilla 41012, Spain

1-methyl-4-phenylpyridinium (MPP+) is the bioactivated product of 1-methyl-4-phenyl- 1, 2, 3, 6-tetrahydropyri dine (MPTP). The neurotoxic action of MPP+ injected intracerebroventricularly (ICV) in the rat has been stud ied, using dopaminergic systems in the substantia nigra, striatum, olfactory bulb, median eminence and hypoph ysis. The following results were obtained: (1) Rats with ICV administration of 1 µl MPP+ solution (62.5 µg of MPP+ rat) showed 50% mortality; (2) The ICV administration of MPP+ produced a decrease in dopamine (DA) concentra tion in different areas of rat CNS studied: striatum (83%), hypophysis (95%) and median eminence (70%). However, olfactory bulb and substantia nigra were not affected; (3) MPP+ by ICV administration produced neurotoxic effect on the dopaminergic system. We also studied the possible protective action of acetyl-L-carnitine (ALC) against the neurotoxic action of MPP+. Rats were intraperitoneally injected daily for 8 days with 100 mg kg-1 of ALC and 3 days from the beginning of the MPP+ treatment; (4) We found that the ALC treatment significantly protected against mortality produced by the ICV injection of MPP+. Rats treated with ALC showed no mortality; (5) We did not find a protective effect on the dopaminergic system study ing either catecholamine concentration or measuring tyro sine hydroxylase, neurofilament or glial fibrillary acid protein; (6) The results suggest that the ALC protective action could be related to energy metabolism.

Key Words: acetyl-L-carnitine • 1-methyl-4-phenylpyri dinium • protection • striatum

Human & Experimental Toxicology, Vol. 14, No. 11, 865-871 (1995)
DOI: 10.1177/096032719501401102


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