title: S-allylcysteine reduces the MPTP-induced striatal cell damage via inhibition of pro-inflammatory cytokine tumor necrosis factor-α and inducible nitric oxide synthase expressions in mice.
abstract: We have recently demonstrated that S-allylcysteine (SAC) induces protection on neurochemical, biochemical and behavioral markers of striatal damage in different neurotoxic animal models - including a murine model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropiridinium (MPTP) injection to mice - indicating that pro-oxidant reactions underlie neurotoxicity in these models (García et al. 2008). In this work we investigated whether SAC can protect the striatum of mice from the morphological alterations in the MPTP toxic model, and if this response is correlated with a reduction in pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) expressions, and further reduction in astrocyte activation (glial fibrillary acidic protein (GFAP) expression). The striatal tissue from MPTP injected animals (30 mg/kg, i.p., ×5 days) showed a significant degree of cell damage and enhanced immunoreactivities to GFAP, TNF-α and iNOS, as well as an enhanced number of apoptotic nuclei. Treatment of mice with SAC (120 mg/kg, i.p., ×5 days) in parallel to MPTP significantly reduced or prevented all these markers. Our results suggest that MPTP-induced morphological alterations recruit a pro-inflammatory component triggered by cytokine TNF-α release and nitric oxide formation, which is sensitive to the antioxidant properties of SAC. This antioxidant is an effective experimental tool to reduce the brain lesions associated with oxidative damage and inflammatory responses.
authors.affiliation: Departamento de Neuroinmunología, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, SSA, México DF, Mexico.
authors.forename: Esperanza
authors.initials: E
authors.lastname: García
authors.forename: Juana
authors.initials: J
authors.lastname: Villeda-Hernández
authors.forename: José
authors.initials: J
authors.lastname: Pedraza-Chaverrí
authors.forename: Perla D
authors.initials: PD
authors.lastname: Maldonado
authors.forename: Abel
authors.initials: A
authors.lastname: Santamaría
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000378:metabolism*; D020267:MPTP Poisoning / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000975:Antioxidants; D018836:Inflammation Mediators; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; C065299:S-allylcysteine; D052247:Nitric Oxide Synthase Type II; D003545:Cysteine