title: Stimulation of lipid peroxidation in vitro in rat brain by the metabolites accumulating in maple syrup urine disease.
abstract: In this study we investigated the in vitro effects of the metabolites accumulating in maple syrup urine disease on lipid peroxidation in brain of young rats. Chemiluminescence and thiobarbituric acid-reactive substances were measured in brain homogenates from 7- and 30-day-old rats in the presence of 10 mM of the branched-chain amino acids L-leucine, L-isoleucine, or L-valine; their keto acids L-2-ketoisocaproic acid, L-2-keto-3-methylvaleric acid, or L-2-ketoisovaleric acid; or the hydroxy derivatives L-2-hydroxyisocaproic acid, L-2-hydroxy-3-methylvaleric acid, or L-2-hydroxyisovaleric acid separately added to the incubation medium. We observed that all amino acids, keto acids, and hydroxy acids accumulating in this disease stimulate to a variable degree the in vitro parameters of lipid peroxidation tested in homogenates of rat brain. The results indicate a possible participation of oxidative stress in the neuropathology of maple syrup urine disease patients, especially during a crisis, when the metabolites are highly increased, and point to the use of antioxidant drugs as a possible adjuvant therapy in such situations to improve the neurological status of the patients and to prevent sequelae.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Fernanda U
authors.initials: FU
authors.lastname: Fontella
authors.forename: Edson
authors.initials: E
authors.lastname: Gassen
authors.forename: Vânia
authors.initials: V
authors.lastname: Pulrolnik
authors.forename: Clóvis M D
authors.initials: CM
authors.lastname: Wannmacher
authors.forename: Adriane B
authors.initials: AB
authors.lastname: Klein
authors.forename: Moacir
authors.initials: M
authors.lastname: Wajner
authors.forename: Carlos S
authors.initials: CS
authors.lastname: Dutra-Filho
mesh_terms: D000597:Amino Acids, Branched-Chain / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008163:Luminescent Measurements; D008375:Maple Syrup Urine Disease / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances
chemical_list: D000597:Amino Acids, Branched-Chain; D009419:Nerve Tissue Proteins; D017392:Thiobarbituric Acid Reactive Substances