title: Zocor Forte (simvastatin) has a neuroprotective effect against LPS striatal dopaminergic terminals injury, whereas against MPP+ does not.
abstract: Due to their potential role in preventing further deterioration of Parkinson's disease, anti-inflammatory strategies have attracted great interest. In this context, some studies point out the possible protective effect of anti-inflammatory compounds against the in vivo degeneration of dopaminergic neurons produced by lipopolysaccharide (LPS)-induced inflammatory processes and others. We have investigated the effect of the treatment of Zocor Forte (simvastatin) in LPS and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurodegenerative models to identify neuroprotective drugs for Parkinson's disease. We have perfused different concentrations of LPS or 1 mM 1-methyl-4-phenylpyridinium ion (MPP+) in the rat's striatum, 24 h after implanting a brain microdialysis probe, both with and without Zocor Forte (simvastatin) treatment. Results show that LPS perfusion produced a decrease in the basal release of dopamine. Forty-eight hours after implanting the probe, we have perfused 1 mM MPP+ to check the integrity of the dopaminergic terminals present around the cannula. Our model to study toxicity in the striatal dopaminergic terminals suggests that Zocor Forte (simvastatin) could prevent the neurotoxic damage produced by LPS, but not that produced by MPP+.
authors.affiliation: Departamento de Bioquímica, Bromatología, Toxicología y Medicina Legal, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain. msantiago@us.es
authors.forename: Marti
authors.initials: M
authors.lastname: Santiago
authors.forename: Mari Carmen
authors.initials: MC
authors.lastname: Hernández-Romero
authors.forename: Alberto
authors.initials: A
authors.lastname: Machado
authors.forename: Josefina
authors.initials: J
authors.lastname: Cano
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000031:analogs & derivatives / Q000378:metabolism; D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D009411:Nerve Endings / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010300:Parkinson Disease / Q000473:pathology; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D019821:Simvastatin / Q000494:pharmacology*
chemical_list: D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; C040846:4-phenyl-1,2,3,6-tetrahydropyridine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D019821:Simvastatin; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine