Lipid peroxidation, mitochondrial dysfunction and neurochemical and behavioural deficits in different neurotoxic models: protective role of S-allylcysteine.
Experimental evidence on the protective properties of S-allylcysteine (SAC) was collected from three models exerting striatal toxicity. In the first model, SAC (120 mg kg(-1)x5) prevented lipoperoxidation (LP) and mitochondrial dysfunction (MD) in synaptosomal fractions from 1-methyl-4-phenyl-1,2,3,6-tetrahydropiridinium-treated mice (30 mg kg(-1)), but without complete restoration of dopamine levels. In the second model, SAC (300 mg kg(-1)x 3), prevented LP and MD in synaptosomes from rats infused with 6-hydroxydopamine (8 microg microl(-1)) into the substantia nigra pars compacta, but again, without total reversion of depleted dopamine levels. In the third model, SAC (100 mg kg(-1)x 1) prevented MD in synaptosomes from rats injected with 3-nitropropionic acid (10 mg kg(-1)), but in contrast to the other models, it failed to prevent LP. SAC also prevented the aberrant motor activity patterns evoked by the three toxins. Altogether, the results suggest that the antioxidant properties of SAC are responsible for partial or total preservation of neurochemical, biochemical and behavioural markers, indicating that pro-oxidant reactions underlie the neurotoxicity in these models.
Garcia
Esperanza
E
Departamento de Neuroinmunología, Instituto Nacional de Neurología y Neurocirugía Manuel VelascoSuárez, SSA, México DF, México.
Limon
Daniel
D
Perez-De La Cruz
Veronica
V
Giordano
Magda
M
Diaz-Muñoz
Mauricio
M
Maldonado
Perla D
PD
Herrera-Mundo
Maria Nieves
MN
Pedraza-Chaverri
Jose
J
Santamaria
Abel
A
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001479:Basal Ganglia / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D020267:MPTP Poisoning / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D009574:Nitro Compounds; D018384:Oxidative Stress / Q000187:drug effects; D016627:Oxidopamine; D011422:Propionates; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes; D013997:Time Factors
D000975:Antioxidants; D015415:Biomarkers; D018696:Neuroprotective Agents; D009574:Nitro Compounds; D011422:Propionates; C065299:S-allylcysteine; D016627:Oxidopamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D003545:Cysteine; C015392:3-nitropropionic acid; D004298:Dopamine