title: Pleiotropic effects of 5-aminolevulinic acid in mouse brain.
abstract: 5-Aminolevulinic acid (ALA) seems to be responsible for the neuropsychiatric manifestations of acute intermittent porphyria (AIP). Our aim was to study the effect of ALA on the different metabolic pathways in the mouse brain to enhance our knowledge about the action of this heme precursor on the central nervous system. Heme metabolism, the cholinergic system, the defense enzyme system, and nitric oxide metabolism were evaluated in the encephalon of CF-1 mice receiving a single (40 mg/kg body mass) or multiple doses of ALA (40 mg/kg, every 48 h for 14 days). We subsequently found ALA accumulation in the encephalon of the mice. ALA also altered the brain cholinergic system. After one dose of ALA, a decrease in superoxide dismutase activity and a reduction in glutathione levels were detected, whereas malondialdehyde levels and catalase activity were increased. Heme oxygenase was also increased as an antioxidant response to protect the encephalon against injury. All nitric oxide synthase isoforms were induced by ALA, these changes were more significant for the inducible isoform in glial cells. In conclusion, ALA affected several metabolic pathways in mouse encephalon. Data indicate that a rapid response to oxidative stress was developed; however, with long-term intoxication, the redox balance was probably restored, thereby minimizing oxidative damage.
authors.affiliation: a Cátedra de Bromatología y Nutrición, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina.
authors.forename: Jimena
authors.initials: J
authors.lastname: Lavandera
authors.affiliation: b Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), CONICET, Hospital de Clínicas, José de San Martín, Universidad de Buenos Aires, Argentina.
authors.forename: Jorge
authors.initials: J
authors.lastname: Rodríguez
authors.affiliation: b Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), CONICET, Hospital de Clínicas, José de San Martín, Universidad de Buenos Aires, Argentina.
authors.forename: Silvina
authors.initials: S
authors.lastname: Ruspini
authors.affiliation: c Departamento de Patología, Instituto de Estudios Oncológicos, Academia Nacional de Medicina, Buenos Aires, Argentina.
authors.forename: Roberto
authors.initials: R
authors.lastname: Meiss
authors.affiliation: b Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), CONICET, Hospital de Clínicas, José de San Martín, Universidad de Buenos Aires, Argentina.
authors.forename: Johanna Romina
authors.initials: JR
authors.lastname: Zuccoli
authors.affiliation: d Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
authors.forename: María Del Carmen
authors.initials: Mdel C
authors.lastname: Martínez
authors.affiliation: b Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), CONICET, Hospital de Clínicas, José de San Martín, Universidad de Buenos Aires, Argentina.
authors.forename: Esther
authors.initials: E
authors.lastname: Gerez
authors.affiliation: b Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), CONICET, Hospital de Clínicas, José de San Martín, Universidad de Buenos Aires, Argentina.
authors.forename: Alcira
authors.initials: A
authors.lastname: Batlle
authors.affiliation: b Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), CONICET, Hospital de Clínicas, José de San Martín, Universidad de Buenos Aires, Argentina.|d Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
authors.forename: Ana María
authors.initials: AM
authors.lastname: Buzaleh
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000622:Aminolevulinic Acid / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006418:Heme / Q000378:metabolism*; D008297:Male; D051379:Mice; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D017319:Photosensitizing Agents / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D017319:Photosensitizing Agents; D006418:Heme; D000622:Aminolevulinic Acid; D019001:Nitric Oxide Synthase; D000110:Acetylcholinesterase
keywords: 5-aminolevulinic acid; acide 5-aminolévulinique; antioxidant defense system; cholinergic system; heme metabolism; métabolisme de l’hème; nitric oxide synthase; synthase d’oxyde nitrique; système cholinergique; système de défense antioxydante