S-Allylcysteine, a garlic-derived antioxidant, ameliorates quinolinic acid-induced neurotoxicity and oxidative damage in rats.
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.
Pérez-Severiano
Francisca
F
Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, México D.F. 14269, Mexico.
Rodríguez-Pérez
Mayra
M
Pedraza-Chaverrí
José
J
Maldonado
Perla D
PD
Medina-Campos
Omar N
ON
Ortíz-Plata
Alma
A
Sánchez-García
Aurora
A
Villeda-Hernández
Juana
J
Galván-Arzate
Sonia
S
Aguilera
Penélope
P
Santamaría
Abel
A
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
D000975:Antioxidants; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C065299:S-allylcysteine; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D017378:Quinolinic Acid; D003545:Cysteine