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Antioxidant strategy to rescue synaptosomes from oxidative damage and energy failure in neurotoxic models in rats: protective role of S-allylcysteine

  • Basic Neurosciences, Genetics and Immunology - Original Article
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Abstract

The functional preservation of nerve endings since the early stages of toxicity in a given damaging insult—either acute or chronic—by means of antioxidant and neuroprotective agents is a primary need to design therapeutic strategies for neurodegenerative disorders, with particular emphasis on those diseases with excitotoxic and depleted energy metabolism components. S-allylcysteine (SAC), a well-known antioxidant agent, was tested as a post-treatment in different in vitro and in vivo neurotoxic models. Quinolinic acid (QUIN) was used as a typical excitotoxic/pro-oxidant inducer, 3-nitropropionic acid (3-NP) was employed as a mitochondrial function inhibitor, and their combination (QUIN + 3-NP) was also evaluated in in vitro studies. For in vitro purposes, increasing concentrations of SAC (10–100 μM) were added to isolated brain synaptosomes at different times (1, 3 and 6 h) after the incubation with toxins (100 μM QUIN, 1 mM 3-NP or the combination of QUIN (21 μM) + 3-NP (166 μM). Thirty minutes later, lipid peroxidation (LP) and mitochondrial dysfunction (MD) were evaluated. For in vivo studies, SAC (100 mg/kg, i.p.) was given to QUIN- or 3-NP-striatally lesioned rats for 7 consecutive days (starting 120 min post-lesion). LP and MD were evaluated 7 days post-lesion in isolated striatal synaptosomes. Circling behavior was also assessed. Our results describe a differential pattern of protection achieved by SAC, mostly expressed in the 3-NP toxic model, in which nerve ending protection was found within the first hours (1 and 3) after the toxic insult started, supporting the concept that the ongoing oxidative damage and energy depletion can be treated during the first stages of neurotoxic events.

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Acknowledgments

This work was supported by CONACyT-México Grants 48370-Q (A.S.) and 48812 (J.P.-Ch). Diana Elinos-Calderón received scholarships from Fundación Armstrong-México and PROBEI, S.S.A.-Mexico.

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Authors and Affiliations

  1. Laboratorio de Aminoácidos Excitadores, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Insurgentes Sur 3877, CP 14269, Mexico, D.F., Mexico

    Diana Elinos-Calderón, Yolanda Robledo-Arratia, Verónica Pérez-De La Cruz & Abel Santamaría

  2. Laboratorio de Patología Vascular Cerebral, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, CP 14269, Mexico, D.F., Mexico

    Perla D. Maldonado

  3. Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, CP 14269, Mexico, D.F., Mexico

    Sonia Galván-Arzate

  4. Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, 04510, Mexico, D.F., Mexico

    José Pedraza-Chaverrí

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  1. Diana Elinos-Calderón
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  2. Yolanda Robledo-Arratia
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  3. Verónica Pérez-De La Cruz
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  4. Perla D. Maldonado
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  6. José Pedraza-Chaverrí
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Correspondence to Abel Santamaría.

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Elinos-Calderón, D., Robledo-Arratia, Y., Pérez-De La Cruz, V. et al. Antioxidant strategy to rescue synaptosomes from oxidative damage and energy failure in neurotoxic models in rats: protective role of S-allylcysteine. J Neural Transm 117, 35–44 (2010). https://doi.org/10.1007/s00702-009-0299-5

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