title: S-Allylcysteine, a garlic-derived antioxidant, ameliorates quinolinic acid-induced neurotoxicity and oxidative damage in rats.
abstract: Excitotoxicity elicited by overactivation of N-methyl-D-aspartate receptors is a well-known characteristic of quinolinic acid-induced neurotoxicity. However, since many experimental evidences suggest that the actions of quinolinic acid also involve reactive oxygen species formation and oxidative stress as major features of its pattern of toxicity, the use of antioxidants as experimental tools against the deleterious effects evoked by this neurotoxin becomes more relevant. In this work, we investigated the effect of a garlic-derived compound and well-characterized free radical scavenger, S-allylcysteine, on quinolinic acid-induced striatal neurotoxicity and oxidative damage. For this purpose, rats were administered S-allylcysteine (150, 300 or 450 mg/kg, i.p.) 30 min before a single striatal infusion of 1 microl of quinolinic acid (240 nmol). The lower dose (150 mg/kg) of S-allylcysteine resulted effective to prevent only the quinolinate-induced lipid peroxidation (P < 0.05), whereas the systemic administration of 300 mg/kg of this compound to rats decreased effectively the quinolinic acid-induced oxidative injury measured as striatal reactive oxygen species formation (P < 0.01) and lipid peroxidation (P < 0.05). S-Allylcysteine (300 mg/kg) also prevented the striatal decrease of copper/zinc-superoxide dismutase activity (P < 0.05) produced by quinolinate. In addition, S-allylcysteine, at the same dose tested, was able to reduce the quinolinic acid-induced neurotoxicity evaluated as circling behavior (P < 0.01) and striatal morphologic alterations. In summary, S-allylcysteine ameliorates the in vivo quinolinate striatal toxicity by a mechanism related to its ability to: (a) scavenge free radicals; (b) decrease oxidative stress; and (c) preserve the striatal activity of Cu,Zn-superoxide dismutase (Cu,Zn-SOD). This antioxidant effect seems to be responsible for the preservation of the morphological and functional integrity of the striatum.
authors.affiliation: Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, México D.F. 14269, Mexico.
authors.forename: Francisca
authors.initials: F
authors.lastname: Pérez-Severiano
authors.forename: Mayra
authors.initials: M
authors.lastname: Rodríguez-Pérez
authors.forename: José
authors.initials: J
authors.lastname: Pedraza-Chaverrí
authors.forename: Perla D
authors.initials: PD
authors.lastname: Maldonado
authors.forename: Omar N
authors.initials: ON
authors.lastname: Medina-Campos
authors.forename: Alma
authors.initials: A
authors.lastname: Ortíz-Plata
authors.forename: Aurora
authors.initials: A
authors.lastname: Sánchez-García
authors.forename: Juana
authors.initials: J
authors.lastname: Villeda-Hernández
authors.forename: Sonia
authors.initials: S
authors.lastname: Galván-Arzate
authors.forename: Penélope
authors.initials: P
authors.lastname: Aguilera
authors.forename: Abel
authors.initials: A
authors.lastname: Santamaría
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western; D001835:Body Weight; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005737:Garlic / Q000737:chemistry*; D005979:Glutathione Peroxidase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000201:enzymology; D020258:Neurotoxicity Syndromes / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects*; D017378:Quinolinic Acid / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C065299:S-allylcysteine; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D017378:Quinolinic Acid; D003545:Cysteine