Tags

Type your tag names separated by a space and hit enter

alpha-keto acids accumulating in maple syrup urine disease stimulate lipid peroxidation and reduce antioxidant defences in cerebral cortex from young rats.
Metab Brain Dis. 2005 Jun; 20(2):155-67.MB

Abstract

Maple syrup urine disease (MSUD) is an inherited neurometabolic disorder caused by deficiency of branched-chain alpha-keto acid dehydrogenase complex activity which leads to tissue accumulation of the branched-chain alpha-keto acids (BCKAs) alpha-ketoisocaproic acid (KIC), alpha-ketoisovaleric acid (KIV) and alpha-keto-beta-methylvaleric acid (KMV) and their respective amino acids. Neuropathologic findings characteristic of the disease are cerebral edema and atrophy, whose pathophysiology is poorly known. In the present study, we investigated the in vitro effect of BCKAs on various parameters of oxidative stress, namely chemiluminescence (CL), thiobarbituric acid-reactive substances (TBA-RS), total radical-trapping antioxidant potential (TRAP), total antioxidant reactivity (TAR), and the activities of the antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) in cerebral cortex of 30-day-old rats. The major effects observed were with KIC, which significantly increased CL and TBA-RS measurements, decreased TRAP and TAR values, and markedly inhibited GPx activity. KMV and KIV increased CL and decreased TRAP and TAR values. In contrast, these compounds did not affect CAT and SOD activities. Taken together, it was shown that: the BCKAs studied stimulated lipid peroxidation and reduced the brain antioxidant defences, suggesting an increased production of free radicals. In case the in vitro effects here detected also occur in vivo in MSUD, it can be presumed that oxidative stress might contribute, at least in part, to the brain damage found in the affected patients.

Authors+Show Affiliations

Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15938133

Citation

Bridi, Raquel, et al. "Alpha-keto Acids Accumulating in Maple Syrup Urine Disease Stimulate Lipid Peroxidation and Reduce Antioxidant Defences in Cerebral Cortex From Young Rats." Metabolic Brain Disease, vol. 20, no. 2, 2005, pp. 155-67.
Bridi R, Braun CA, Zorzi GK, et al. Alpha-keto acids accumulating in maple syrup urine disease stimulate lipid peroxidation and reduce antioxidant defences in cerebral cortex from young rats. Metab Brain Dis. 2005;20(2):155-67.
Bridi, R., Braun, C. A., Zorzi, G. K., Wannmacher, C. M., Wajner, M., Lissi, E. G., & Dutra-Filho, C. S. (2005). Alpha-keto acids accumulating in maple syrup urine disease stimulate lipid peroxidation and reduce antioxidant defences in cerebral cortex from young rats. Metabolic Brain Disease, 20(2), 155-67.
Bridi R, et al. Alpha-keto Acids Accumulating in Maple Syrup Urine Disease Stimulate Lipid Peroxidation and Reduce Antioxidant Defences in Cerebral Cortex From Young Rats. Metab Brain Dis. 2005;20(2):155-67. PubMed PMID: 15938133.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - alpha-keto acids accumulating in maple syrup urine disease stimulate lipid peroxidation and reduce antioxidant defences in cerebral cortex from young rats. AU - Bridi,Raquel, AU - Braun,César A, AU - Zorzi,Giovanni K, AU - Wannmacher,Clóvis M D, AU - Wajner,Moacir, AU - Lissi,Eduardo G, AU - Dutra-Filho,Carlos Severo, PY - 2005/6/9/pubmed PY - 2005/8/19/medline PY - 2005/6/9/entrez SP - 155 EP - 67 JF - Metabolic brain disease JO - Metab Brain Dis VL - 20 IS - 2 N2 - Maple syrup urine disease (MSUD) is an inherited neurometabolic disorder caused by deficiency of branched-chain alpha-keto acid dehydrogenase complex activity which leads to tissue accumulation of the branched-chain alpha-keto acids (BCKAs) alpha-ketoisocaproic acid (KIC), alpha-ketoisovaleric acid (KIV) and alpha-keto-beta-methylvaleric acid (KMV) and their respective amino acids. Neuropathologic findings characteristic of the disease are cerebral edema and atrophy, whose pathophysiology is poorly known. In the present study, we investigated the in vitro effect of BCKAs on various parameters of oxidative stress, namely chemiluminescence (CL), thiobarbituric acid-reactive substances (TBA-RS), total radical-trapping antioxidant potential (TRAP), total antioxidant reactivity (TAR), and the activities of the antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) in cerebral cortex of 30-day-old rats. The major effects observed were with KIC, which significantly increased CL and TBA-RS measurements, decreased TRAP and TAR values, and markedly inhibited GPx activity. KMV and KIV increased CL and decreased TRAP and TAR values. In contrast, these compounds did not affect CAT and SOD activities. Taken together, it was shown that: the BCKAs studied stimulated lipid peroxidation and reduced the brain antioxidant defences, suggesting an increased production of free radicals. In case the in vitro effects here detected also occur in vivo in MSUD, it can be presumed that oxidative stress might contribute, at least in part, to the brain damage found in the affected patients. SN - 0885-7490 UR - https://www.unboundmedicine.com/medline/citation/15938133/alpha_keto_acids_accumulating_in_maple_syrup_urine_disease_stimulate_lipid_peroxidation_and_reduce_antioxidant_defences_in_cerebral_cortex_from_young_rats_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=15938133.ui DB - PRIME DP - Unbound Medicine ER -