title: Striatum is more vulnerable to oxidative damage induced by the metabolites accumulating in 3-hydroxy-3-methylglutaryl-CoA lyase deficiency as compared to liver.
abstract: The present work investigated the in vitro effects of 3-hydroxy-3-methylglutarate, 3-methylglutarate, 3-methylglutaconate and 3-hydroxyisovalerate, which accumulate in 3-hydroxy-3-methylglutaric aciduria, on important parameters of oxidative stress in striatum and liver of young rats, tissues that are injured in this disorder. Our results show that all metabolites induced lipid peroxidation (thiobarbituric acid-reactive substances increase) and decreased glutathione levels in striatum, whereas 3-hydroxy-3-methylglutarate, besides inducing the strongest effect, also altered thiobarbituric acid-reactive substances and glutathione levels in the liver. Furthermore, 3-hydroxy-3-methylglutarate, 3-methylglutarate and 3-methylglutaconate oxidized sulfhydryl groups in the striatum, but not in the liver. Our data indicate that 3-hydroxy-3-methylglutarate behaves as a stronger pro-oxidant agent compared to the other metabolites accumulating in 3-hydroxy-3-methylglutaric aciduria and that the striatum present higher vulnerability to oxidative damage relatively to the liver.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil.
authors.forename: Guilhian
authors.initials: G
authors.lastname: Leipnitz
authors.forename: Bianca
authors.initials: B
authors.lastname: Seminotti
authors.forename: Carolina G
authors.initials: CG
authors.lastname: Fernandes
authors.forename: Alexandre U
authors.initials: AU
authors.lastname: Amaral
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Beskow
authors.forename: Lucila de B
authors.initials: Lde B
authors.lastname: da Silva
authors.forename: Angela
authors.initials: A
authors.lastname: Zanatta
authors.forename: César A J
authors.initials: CA
authors.lastname: Ribeiro
authors.forename: Carmen R
authors.initials: CR
authors.lastname: Vargas
authors.forename: Moacir
authors.initials: M
authors.lastname: Wajner
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D005977:Glutarates / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D015093:Meglutol / Q000031:analogs & derivatives / Q000378:metabolism; D018384:Oxidative Stress; D007652:Oxo-Acid-Lyases / Q000172:deficiency* / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014631:Valerates / Q000378:metabolism
chemical_list: D005977:Glutarates; D017392:Thiobarbituric Acid Reactive Substances; D014631:Valerates; C002163:beta-methylcrotonylglycine; C004961:beta-hydroxyisovaleric acid; C033686:3-methylglutaric acid; C022034:3-methylglutaconic acid; D015093:Meglutol; D007652:Oxo-Acid-Lyases; C021410:3-hydroxy-3-methylglutaryl-coenzyme A lyase; D005978:Glutathione; D005998:Glycine