title: L-NAME cotreatment did prevent neither mitochondrial impairment nor behavioral abnormalities in adult Wistar rats treated with vitamin A supplementation.
abstract: Vitamin A has been characterized as a potential neurotoxin, because ingestion of such vitamin - or its derivatives, the retinoids - at moderate to high doses elicits a myriad of deleterious effects, from acute intoxication involving head-ache, confusion, and 'pseudo tumor cerebri' to chronic, and perhaps irreversible, abnormalities, including irritability, anxiety, depression, and suicide ideation. Nevertheless, it still remains to be found the mechanism by which vitamin A induces cognitive decline. Based on the fact that vitamin A at clinical doses is a potent pro-oxidant agent to the central nervous system, we performed the present work to analyze whether a cotreatment with L-NAME at 30 mg/kg (four times a week) was able to prevent (or minimize) the biochemical and/or behavioral disturbances resulting from a 28-day daily supplementation with retinol palmitate at doses from 1000 to 9000 IU/kg/day. Then, we investigated mitochondrial function, redox parameters, and the levels of proteins potentially involved in neurodegenerative events, as for instance α-synuclein and receptor for advanced glycation endproducts. Besides, monoamine oxidase enzyme activity was quantified in this work. We observed that L-NAME cotreatment was not completely effective in preventing the redox disturbances induced by vitamin A supplementation. Moreover, L-NAME cotreatment did not affect the behavioral deficits elicited by vitamin A supplementation. We conclude that other parameters rather than NO levels or its derivatives, as for example ONOO(-), take a more important role in mediating the negative effects triggered by vitamin A supplementation.
authors.affiliation: Centro de Estudos em Estresse Oxidativo (Lab. 32), Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil. mrobioq@yahoo.com.br
authors.forename: Marcos Roberto
authors.initials: MR
authors.lastname: de Oliveira
authors.forename: Ricardo Fagundes
authors.initials: RF
authors.lastname: da Rocha
authors.forename: Carlos Eduardo
authors.initials: CE
authors.lastname: Schnorr
authors.forename: José Cláudio Fonseca
authors.initials: JC
authors.lastname: Moreira
mesh_terms: D000818:Animals; D001008:Anxiety Disorders / Q000139:chemically induced / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects*; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism; D019587:Dietary Supplements / Q000009:adverse effects*; D004224:Diterpenes; D004579:Electron Transport / Q000187:drug effects; D005982:Glutathione Transferase / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D055809:Illness Behavior / Q000187:drug effects; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008345:Manganese / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects*; D008995:Monoamine Oxidase / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019636:Neurodegenerative Diseases / Q000139:chemically induced; D009569:Nitric Oxide / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D000067759:Receptor for Advanced Glycation End Products; D011954:Receptors, Dopamine / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D000084562:Retinyl Esters; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014801:Vitamin A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D051844:alpha-Synuclein / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D004224:Diterpenes; D005982:Glutathione Transferase; D006360:Heat-Shock Proteins; D008345:Manganese; D008995:Monoamine Oxidase; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide; D000067759:Receptor for Advanced Glycation End Products; D011954:Receptors, Dopamine; D011971:Receptors, Immunologic; D000084562:Retinyl Esters; D013482:Superoxide Dismutase; D013481:Superoxides; D014443:Tyrosine; D014801:Vitamin A; D051844:alpha-Synuclein; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C014794:retinol palmitate; C002744:3-nitrotyrosine