Striatum is more vulnerable to oxidative damage induced by the metabolites accumulating in 3-hydroxy-3-methylglutaryl-CoA lyase deficiency as compared to liver.
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.
Leipnitz
Guilhian
G
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil.
Seminotti
Bianca
B
Fernandes
Carolina G
CG
Amaral
Alexandre U
AU
Beskow
Ana Paula
AP
da Silva
Lucila de B
Lde B
Zanatta
Angela
A
Ribeiro
César A J
CA
Vargas
Carmen R
CR
Wajner
Moacir
M
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
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