Induction of oxidative stress by the metabolites accumulating in isovaleric acidemia in brain cortex of young rats.
The present work investigated the in vitro effects of isovaleric acid (IVA) and isovalerylglycine (IVG), which accumulate in isovaleric acidemia (IVAcidemia), on important parameters of oxidative stress in supernatants and mitochondrial preparations from brain of 30-day-old rats. IVG, but not IVA, significantly increased TBA-RS and chemiluminescence values in cortical supernatants. Furthermore, the addition of free radical scavengers fully prevented IVG-induced increase of TBA-RS. IVG also decreased GSH concentrations, whereas IVA did not modify this parameter in brain supernatants. Furthermore, IVG did not alter lipid peroxidation or GSH concentrations in mitochondrial preparations, indicating that the generation of oxidants by IVG was dependent on cytosolic mechanisms. On the other hand, IVA significantly induced carbonyl formation both in supernatants and purified mitochondrial preparations from rat brain, with no effect observed for IVG. Therefore, it is presumed that oxidative damage may be at least in part involved in the pathophysiology of the neuropathology of IVAcidemia.
Solano
Alexandre F
AF
Departamento de Bioquimica, Instituto de Ciencias Basicas da Saude, UFRGS, Porto Alegre, RS, Brazil.
Leipnitz
Guilhian
G
De Bortoli
Giorgia M
GM
Seminotti
Bianca
B
Amaral
Alexandre U
AU
Fernandes
Carolina G
CG
Latini
Alexandra S
AS
Dutra-Filho
Carlos S
CS
Wajner
Moacir
M
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D045782:Hemiterpenes; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008661:Metabolism, Inborn Errors / Q000378:metabolism / Q000473:pathology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010421:Pentanoic Acids / Q000494:pharmacology*; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D016166:Free Radical Scavengers; D045782:Hemiterpenes; D010421:Pentanoic Acids; D017392:Thiobarbituric Acid Reactive Substances; C008216:isovaleric acid; C005916:N-isovalerylglycine; D005978:Glutathione; D005998:Glycine