caa a22 4500 463254554 CHVBK 20180405153351.0 cr unu---uuuuu 170326e20070601xx s 000 0 eng 10.1007/s10571-006-9134-9 doi (NATIONALLICENCE)springer-10.1007/s10571-006-9134-9 Induction of Oxidative Stress by Chronic and Acute Glutaric Acid Administration to Rats [Elektronische Daten] [Alexandra Latini, Gustavo C. Ferreira, Karina Scussiato, Patrícia F. Schuck, Alexandre F. Solano, Carlos S. Dutra-Filho, Carmen R. Vargas, Moacir Wajner] : 1. Glutaric acidemia type I (GA I) is a neurometabolic disorder caused by deficiency of glutaryl-CoA dehydrogenase, which leads to tissue accumulation of predominantly glutaric acid (GA) and also 3-hydroxyglutaric acid to a lesser amount. Affected patients usually present progressive cortical atrophy and acute striatal degeneration attributed to the toxic accumulating metabolites. 2. In the present study, we determined a number of oxidative stress parameters, namely chemiluminescence, thiobarbituric acid-reactive substances (TBA-RS), total antioxidant reactivity (TAR), glutathione (GSH) levels, and the activities of catalase and glutathione peroxidase (GPx), in various tissues from rats chronically exposed to GA or to saline (controls). High GA concentrations, similar to those found in glutaric aciduria type I, were induced in the brain by three daily subcutaneous injections of saline-buffered GA (5μmol/g body weight) to Wistar rats of 5-22 days of life. The parameters were assessed 12h after the last GA administration in different brain structures, skeletal muscle, heart, liver, erythrocytes, and plasma. The lipid peroxidation parameters chemiluminescence and/or TBA-RS measurements were found significantly increased in midbrain, liver, and erythrocytes of GA-injected rats. The activity of GPx was significantly reduced in midbrain and markedly increased in liver. TAR measurement was significantly reduced in midbrain and liver. Furthermore, GSH levels were reduced in liver and heart. We also investigated the acute in vivo effect of GA administration on the same oxidative stress parameters in cerebral structures and erythrocytes from 22-day-old rats. We found that TBA-RS values were significantly increased in erythrocytes, TAR levels were markedly decreased in midbrain and cerebellum, and GPx activity mildly reduced in the midbrain. 3. These data showing an imbalance between antioxidant defences and oxidative damage, particularly in midbrain, liver, and erythrocytes from GA-injected rats, indicate that oxidative stress might be involved in GA toxicity and that the midbrain, where the striatum is located, is the brain structure more susceptible to GA chronic and acute exposition. Springer Science+Business Media, LLC, 2007 glutaric acid nationallicence glutaric acidemia type I nationallicence striatum degeneration nationallicence oxidative stress nationallicence Latini Alexandra Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 Anexo, Porto Alegre, RS, Brazil aut Ferreira Gustavo C. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 Anexo, Porto Alegre, RS, Brazil aut Scussiato Karina Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 Anexo, Porto Alegre, RS, Brazil aut Schuck Patrícia F. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 Anexo, Porto Alegre, RS, Brazil aut Solano Alexandre F. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 Anexo, Porto Alegre, RS, Brazil aut Dutra-Filho Carlos S. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 Anexo, Porto Alegre, RS, Brazil aut Vargas Carmen R. Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil aut Wajner Moacir Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 Anexo, Porto Alegre, RS, Brazil aut Cellular and Molecular Neurobiology Kluwer Academic Publishers-Plenum Publishers; http://www.springer-ny.com 27/4(2007-06-01), 423-438 0272-4340 27:4<423 2007 27 10571 https://doi.org/10.1007/s10571-006-9134-9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10571-006-9134-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Latini Alexandra Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 Anexo, Porto Alegre, RS, Brazil aut NATIONALLICENCE 700 1- Ferreira Gustavo C. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 Anexo, Porto Alegre, RS, Brazil aut NATIONALLICENCE 700 1- Scussiato Karina Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 Anexo, Porto Alegre, RS, Brazil aut NATIONALLICENCE 700 1- Schuck Patrícia F. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 Anexo, Porto Alegre, RS, Brazil aut NATIONALLICENCE 700 1- Solano Alexandre F. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 Anexo, Porto Alegre, RS, Brazil aut NATIONALLICENCE 700 1- Dutra-Filho Carlos S. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 Anexo, Porto Alegre, RS, Brazil aut NATIONALLICENCE 700 1- Vargas Carmen R. Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil aut NATIONALLICENCE 700 1- Wajner Moacir Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 Anexo, Porto Alegre, RS, Brazil aut NATIONALLICENCE 773 0- Cellular and Molecular Neurobiology Kluwer Academic Publishers-Plenum Publishers; http://www.springer-ny.com 27/4(2007-06-01), 423-438 0272-4340 27:4<423 2007 27 10571 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer