Excitotoxicity and disrupted energy metabolism are major events leading to nerve cell death in neurodegenerative disorders. These cooperative pathways share one common aspect: triggering of oxidative stress by free radical formation. In this work, we evaluated the effects of the antioxidant and energy precursor, levocarnitine (l‐CAR), on the oxidative damage and the behavioral, morphological, and neurochemical alterations produced in nerve tissue by the excitotoxin and free radical precursor, quinolinic acid (2,3‐pyrindin dicarboxylic acid; QUIN), and the mitochondrial toxin, 3‐nitropropionic acid (3‐NP). Oxidative damage was assessed by the estimation of reactive oxygen species formation, lipid peroxidation, and mitochondrial dysfunction in synaptosomal fractions. Behavioral, morphological, and neurochemical alterations were evaluated as markers of neurotoxicity in animals systemically administered with l‐CAR, chronically injected with 3‐NP and/or intrastriatally infused with QUIN. At micromolar concentrations, l‐CAR reduced the three markers of oxidative stress stimulated by both toxins alone or in combination. l‐CAR also prevented the rotation behavior evoked by QUIN and the hypokinetic pattern induced by 3‐NP in rats. Morphological alterations produced by both toxins (increased striatal glial fibrillary acidic protein‐immunoreactivity for QUIN and enhanced neuronal damage in different brain regions for 3‐NP) were reduced by l‐CAR. In addition, l‐CAR prevented the synergistic action of 3‐NP and QUIN to increase motor asymmetry and depleted striatal GABA levels. Our results suggest that the protective properties of l‐CAR in the neurotoxic models tested are mostly mediated by its characteristics as an antioxidant agent.

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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.

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