Brain and muscle redox imbalance elicited by acute ethylmalonic acid administration

• Published in: PloS one Vol. 10; no. 5; p. e0126606
• Main Authors: Schuck, Patrícia Fernanda, Milanez, Ana Paula, Felisberto, Francine, Galant, Leticia Selinger, Machado, Jéssica Luca, Furlanetto, Camila Brulezi, Petronilho, Fabricia, Dal-Pizzol, Felipe, Streck, Emilio Luiz, Ferreira, Gustavo Costa
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 26.05.2015; Public Library of Science (PLoS)
• Subjects: Acids; Acyl-CoA dehydrogenase; Animal tissues; Animals; Bioaccumulation; Brain; Brain - drug effects; Brain - metabolism; Brain damage; Brain injury; Carbonyl compounds; Carbonyls; Cerebral cortex; Cerebral Cortex - drug effects; Cerebral Cortex - enzymology; Disease; Electron transport; Electron transport chain; Electron Transport Chain Complex Proteins - metabolism; Encephalopathy; Fibroblasts; Fluoresceins - metabolism; Glutathione; Glutathione - metabolism; Glutathione peroxidase; Health aspects; Illnesses; Laboratory animals; Lipid peroxidation; Lipids; Male; Malonates; Malonates - administration & dosage; Malonates - adverse effects; Metabolism; Metabolites; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Muscle Proteins - metabolism; Muscle, Skeletal - enzymology; Muscle, Skeletal - metabolism; Muscles; Musculoskeletal system; Neuromuscular diseases; Oxidation; Oxidation-Reduction; Oxidative stress; Patients; Peroxidase; Peroxidation; Physiological aspects; Protein Carbonylation - drug effects; Rats; Rats, Wistar; Rodents; Skeletal muscle; Sulfhydryl Compounds - metabolism; Superoxide; Superoxides - metabolism; Thiobarbituric acid; Thiobarbituric Acid Reactive Substances - metabolism; Brazil
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0126606

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.