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Evaluation of the mechanisms involved in leucine-induced oxidative damage in cerebral cortex of young rats.
Free Radic Res. 2005 Jan; 39(1):71-9.FR

Abstract

Maple syrup urine disease (MSUD) is a metabolic disorder caused by the deficiency of the activity of the mitochondrial enzyme complex branched-chain L-2-keto acid dehydrogenase. The metabolic block results in tissue and body fluid accumulation of the branched-chain amino acids leucine (Leu), isoleucine and valine, as well as of their respective alpha-keto acids. Neurological sequelae are usually present in MSUD, but the pathophysiologic mechanisms of neurotoxicity are still poorly known. It was previously demonstrated that Leu elicits oxidative stress in rat brain. In the present study we investigated the possible mechanisms involved in Leu-induced oxidative damage. We observed a significant attenuation of Leu-elicited increase of thiobarbituric acid-reactive substances (TBA-RS) measurement when cortical homogenates were incubated in the presence of the free radical scavengers ascorbic acid plus trolox, dithiothreitol, glutathione, and superoxide dismutase, suggesting a probable involvement of superoxide and hydroxyl radicals in this effect. In contrast, the use of Nomega-nitro-L-arginine methyl ester or catalase (CAT) did not affect TBA-RS values. We also demonstrated an inhibitory effect of Leu on the activities of the antioxidant enzymes CAT and gluthathione peroxidase, as well as a significant reduction in the membrane-protein thiol content from mitochondrial enriched preparations. Furthermore, dichlorofluorescein levels were increased although not significantly by Leu. Taken together, our present data indicate that an unbalance between free radical formation and inhibition of critical enzyme activities may explain the mechanisms involved in the Leu-induced oxidative damage.

Authors+Show Affiliations

Departamento de Bioquimica, Instituto de Ciências Báisicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 Anexo, CEP 90035-003, 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

15875814

Citation

Bridi, Raquel, et al. "Evaluation of the Mechanisms Involved in Leucine-induced Oxidative Damage in Cerebral Cortex of Young Rats." Free Radical Research, vol. 39, no. 1, 2005, pp. 71-9.
Bridi R, Latini A, Braum CA, et al. Evaluation of the mechanisms involved in leucine-induced oxidative damage in cerebral cortex of young rats. Free Radic Res. 2005;39(1):71-9.
Bridi, R., Latini, A., Braum, C. A., Zorzi, G. K., Moacir, W., Lissi, E., & Dutra-Filho, C. S. (2005). Evaluation of the mechanisms involved in leucine-induced oxidative damage in cerebral cortex of young rats. Free Radical Research, 39(1), 71-9.
Bridi R, et al. Evaluation of the Mechanisms Involved in Leucine-induced Oxidative Damage in Cerebral Cortex of Young Rats. Free Radic Res. 2005;39(1):71-9. PubMed PMID: 15875814.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evaluation of the mechanisms involved in leucine-induced oxidative damage in cerebral cortex of young rats. AU - Bridi,Raquel, AU - Latini,Alexandra, AU - Braum,Cesar A, AU - Zorzi,Giovanni K, AU - Moacir,Wajner, AU - Lissi,Eduardo, AU - Dutra-Filho,Carlos Severo, PY - 2005/5/7/pubmed PY - 2005/7/26/medline PY - 2005/5/7/entrez SP - 71 EP - 9 JF - Free radical research JO - Free Radic Res VL - 39 IS - 1 N2 - Maple syrup urine disease (MSUD) is a metabolic disorder caused by the deficiency of the activity of the mitochondrial enzyme complex branched-chain L-2-keto acid dehydrogenase. The metabolic block results in tissue and body fluid accumulation of the branched-chain amino acids leucine (Leu), isoleucine and valine, as well as of their respective alpha-keto acids. Neurological sequelae are usually present in MSUD, but the pathophysiologic mechanisms of neurotoxicity are still poorly known. It was previously demonstrated that Leu elicits oxidative stress in rat brain. In the present study we investigated the possible mechanisms involved in Leu-induced oxidative damage. We observed a significant attenuation of Leu-elicited increase of thiobarbituric acid-reactive substances (TBA-RS) measurement when cortical homogenates were incubated in the presence of the free radical scavengers ascorbic acid plus trolox, dithiothreitol, glutathione, and superoxide dismutase, suggesting a probable involvement of superoxide and hydroxyl radicals in this effect. In contrast, the use of Nomega-nitro-L-arginine methyl ester or catalase (CAT) did not affect TBA-RS values. We also demonstrated an inhibitory effect of Leu on the activities of the antioxidant enzymes CAT and gluthathione peroxidase, as well as a significant reduction in the membrane-protein thiol content from mitochondrial enriched preparations. Furthermore, dichlorofluorescein levels were increased although not significantly by Leu. Taken together, our present data indicate that an unbalance between free radical formation and inhibition of critical enzyme activities may explain the mechanisms involved in the Leu-induced oxidative damage. SN - 1071-5762 UR - https://www.unboundmedicine.com/medline/citation/15875814/Evaluation_of_the_mechanisms_involved_in_leucine_induced_oxidative_damage_in_cerebral_cortex_of_young_rats_ L2 - https://www.tandfonline.com/doi/full/10.1080/10715760400022350 DB - PRIME DP - Unbound Medicine ER -