title: Brain and muscle redox imbalance elicited by acute ethylmalonic acid administration.
abstract: Ethylmalonic acid (EMA) accumulates in tissues and biological fluids of patients affected by short-chain acyl-CoA dehydrogenase deficiency (SCADD) and ethylmalonic encephalopathy, illnesses characterized by neurological and muscular symptoms. Considering that the mechanisms responsible for the brain and skeletal muscle damage in these diseases are poorly known, in the present work we investigated the effects of acute EMA administration on redox status parameters in cerebral cortex and skeletal muscle from 30-day-old rats. Animals received three subcutaneous injections of EMA (6 μmol/g; 90 min interval between injections) and were killed 1 h after the last administration. Control animals received saline in the same volumes. EMA administration significantly increased thiobarbituric acid-reactive substances levels in cerebral cortex and skeletal muscle, indicating increased lipid peroxidation. In addition, carbonyl content was increased in EMA-treated animal skeletal muscle when compared to the saline group. EMA administration also significantly increased 2',7'-dihydrodichlorofluorescein oxidation and superoxide production (reactive species markers), and decreased glutathione peroxidase activity in cerebral cortex, while glutathione levels were decreased only in skeletal muscle. On the other hand, respiratory chain complex I-III activity was altered by acute EMA administration neither in cerebral cortex nor in skeletal muscle. The present results show that acute EMA administration elicits oxidative stress in rat brain and skeletal muscle, suggesting that oxidative damage may be involved in the pathophysiology of the brain and muscle symptoms found in patients affected by SCADD and ethylmalonic encephalopathy.
authors.affiliation: Laboratório de Erros Inatos do Metabolismo, Programa de Pós-graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, Santa Catarina, Brazil.
authors.forename: Patrícia Fernanda
authors.initials: PF
authors.lastname: Schuck
authors.affiliation: Laboratório de Erros Inatos do Metabolismo, Programa de Pós-graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, Santa Catarina, Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Milanez
authors.affiliation: Laboratório de Fisiopatologia Experimental, Programa de Pós-graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, Santa Catarina, Brazil.
authors.forename: Francine
authors.initials: F
authors.lastname: Felisberto
authors.affiliation: Laboratório de Fisiopatologia Experimental, Programa de Pós-graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, Santa Catarina, Brazil.
authors.forename: Leticia Selinger
authors.initials: LS
authors.lastname: Galant
authors.affiliation: Laboratório de Erros Inatos do Metabolismo, Programa de Pós-graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, Santa Catarina, Brazil.
authors.forename: Jéssica Luca
authors.initials: JL
authors.lastname: Machado
authors.affiliation: Laboratório de Erros Inatos do Metabolismo, Programa de Pós-graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, Santa Catarina, Brazil.
authors.forename: Camila Brulezi
authors.initials: CB
authors.lastname: Furlanetto
authors.affiliation: Laboratório de Imunopatologia Clínica e Experimental, Programa de Pós-graduação em Ciências da Saúde, Universidade do Sul de Santa Catarina, Tubarão, Santa Catarina, Brazil.
authors.forename: Fabricia
authors.initials: F
authors.lastname: Petronilho
authors.affiliation: Laboratório de Fisiopatologia Experimental, Programa de Pós-graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, Santa Catarina, Brazil.
authors.forename: Felipe
authors.initials: F
authors.lastname: Dal-Pizzol
authors.affiliation: Laboratório de Bioenergética, Programa de Pós-graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, Santa Catarina, Brazil.
authors.forename: Emilio Luiz
authors.initials: EL
authors.lastname: Streck
authors.affiliation: Laboratório de Neuroquímica, Instituto de Biofísica Carlos Chagas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Gustavo Costa
authors.initials: GC
authors.lastname: Ferreira
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D005452:Fluoresceins / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D008297:Male; D008314:Malonates / Q000008:administration & dosage* / Q000009:adverse effects*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism*; D010084:Oxidation-Reduction; D050050:Protein Carbonylation / Q000187:drug effects; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D045222:Electron Transport Chain Complex Proteins; D005452:Fluoresceins; D008314:Malonates; D009124:Muscle Proteins; D013438:Sulfhydryl Compounds; D017392:Thiobarbituric Acid Reactive Substances; C065013:2',7'-dichlorodihydrofluorescein; D013481:Superoxides; C038080:ethylmalonic acid; D005978:Glutathione