Proline impairs energy metabolism in cerebral cortex of young rats.
In the present study we investigated the effect of acute hyperprolinemia on some parameters of energy metabolism, including the activities of succinate dehydrogenase and cytocrome c oxidase and (14)CO(2) production from glucose and acetate in cerebral cortex of young rats. Lipid peroxidation determined by the levels of thiobarbituric acid-reactive substances, as well as the influence of the antioxidants alpha-tocopherol plus ascorbic acid on the effects elicited by Pro on enzyme activities and on the lipid peroxidation were also evaluated. Wistar rats of 12 and 29 days of life received one subcutaneous injection of saline or proline (12.8 or 18.2 micromol/g body weight, respectively) and were sacrificed 1 h later. In another set of experiments, 5- and 22-day-old rats were pretreated for a week with daily intraperitoneal administration of alpha-tocopherol (40 mg/kg) plus ascorbic acid (100 mg/kg) or saline. Twelve hours after the last injection, rats received one injection of proline or saline and were sacrificed 1 h later. Results showed that acute administration of proline significantly reduced cytochrome c oxidase activity and increased succinate dehydrogenase activity and (14)CO(2) production in cerebral cortex, suggesting that Pro might disrupt energy metabolism in brain of young rats. In addition, proline administration increased the thiobarbituric acid-reactive substances levels, which were prevented by antioxidants. These findings suggest that mitochondrial dysfunction and oxidative stress may be important contributors to the neurological dysfunction observed in some hyperprolinemic patients and that treatment with antioxidants may be beneficial in this pathology.
Ferreira
Andréa G K
AG
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Lima
Daniela D
DD
Delwing
Débora
D
Mackedanz
Vanize
V
Tagliari
Bárbara
B
Kolling
Janaína
J
Schuck
Patrícia F
PF
Wajner
Moacir
M
Wyse
Angela T S
AT
D000367:Age Factors; D000375:Aging / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D001205:Ascorbic Acid / Q000494:pharmacology / Q000627:therapeutic use; D001928:Brain Diseases, Metabolic / Q000139:chemically induced / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D004195:Disease Models, Animal; D004357:Drug Synergism; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011392:Proline / Q000009:adverse effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D024502:alpha-Tocopherol / Q000494:pharmacology / Q000627:therapeutic use
D000975:Antioxidants; D017392:Thiobarbituric Acid Reactive Substances; D011392:Proline; D024502:alpha-Tocopherol; D001205:Ascorbic Acid