Glutaric acid administration impairs energy metabolism in midbrain and skeletal muscle of young rats.
A genetic mice model of glutaric acidemia type I (GAI) has recently been developed, however affected animals do not develop the striatal damage characteristic of patients with this disorder. Therefore, the initial aim of the present work was to induce high glutaric acid (GA) concentrations in rat brain similar to those found in GAI patients through subcutaneous injection of GA. High brain GA concentrations (up to 0.60 micromol/g congruent with 0.60mM) were achieved by a single subcutaneous injection of saline-buffered GA (5 micromol/g body weight) to Wistar rats of 7-22 days of life. GA brain levels were about 10-fold lower than in plasma and 5-fold lower than in skeletal and cardiac muscles, indicating that the permeability of the blood brain barrier to GA is low. We also aimed to use this model to investigate neurochemical parameters in the animals. Thus, we evaluated the effect of this model on energy metabolism parameters in midbrain, in which the striatum is localized, as well as in peripheral tissues (skeletal and cardiac muscles) of 22-day-old rats. Control rats were treated with saline in the same volumes. We verified that CO2 production from glucose was not altered in midbrain of rats treated with GA, indicating a normal functioning of the tricarboxylic acid cycle. Creatine kinase activity was also not changed in midbrain, skeletal and cardiac muscles. In contrast, complex I-III activity of the respiratory chain was inhibited in midbrain (25%), while complexes I-III (25%) and II-III (15%) activities were reduced in skeletal muscle, with no alterations found in cardiac muscle. These data indicate that GA administration moderately impairs cellular energy metabolism in midbrain and skeletal muscle of young rats.
Ferreira
Gustavo da C
Gda C
Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Viegas
Carolina M
CM
Schuck
Patrícia F
PF
Tonin
Anelise
A
Ribeiro
César A J
CA
Coelho
Daniella de M
Dde M
Dalla-Costa
Teresa
T
Latini
Alexandra
A
Wyse
Angela T S
AT
Wannmacher
Clovis M D
CM
Vargas
Carmen R
CR
Wajner
Moacir
M
D000818:Animals; D020739:Brain Diseases, Metabolic, Inborn / Q000235:genetics / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D004195:Disease Models, Animal; D004579:Electron Transport / Q000502:physiology; D004734:Energy Metabolism; D005977:Glutarates / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008636:Mesencephalon / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D002250:Carbon Radioisotopes; D005977:Glutarates; D002245:Carbon Dioxide; D003402:Creatine Kinase; C035736:glutaric acid