Navegando por Palavras-chave "succinate dehydrogenase"
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- ItemSomente MetadadadosAscorbic acid and alpha-tocopherol attenuate methylmalonic acid-induced convulsions(Lippincott Williams & Wilkins, 1999-07-13) Fighera, M. R.; Queiroz, C. M.; Stracke, M. P.; Brauer, MCN; Gonzalez-Rodriguez, L. L.; Frussa, R.; Wajner, M.; Mello, C. F. de; Universidade Federal de Sergipe (UFS); Universidade Federal de São Paulo (UNIFESP); Univ Fed Rio Grande SulTHE effects of chronic administration of alpha-tocopherol or melatonin, or acute ascorbic acid administration on the convulsant action of methylmalonic acid (MMA) were investigated in adult male rats. Animals were chronically injected with alpha-tocopherol (40 mg kg(-1), i.p.), melatonin (5 mg kg(-1), i.p.) or vehicle for 7 days. Buffered MMA (6 mu mol/2 mu l) or NaCl (9 mu mol/2 mu l) was injected intrastriatally and the animals were observed for the appearance of clonic or tonic-clonic convulsions and rotational behavior. Ascorbic acid (100 mg kg(-1), s.c.) was administered 30 min before MMA injection. alpha-Tocopherol and ascorbic acid pretreatment decreased the duration of the convulsive episodes and the rotational behavior elicited by MMA, This study provides evidence that free radical generation may participate in the convulsant effects of methylmalonic acid. NeuroReport 10:2039-2043 (C) 1999 Lippincott Williams & Wilkins.
- ItemSomente MetadadadosEffects of short-term zidovudine exposure on mitochondrial DNA content and succinate dehydrogenase activity of rat skeletal muscle cells(Elsevier B.V., 2008-05-15) Kiyomoto, Beatriz H. [UNIFESP]; Tengan, Celia H. [UNIFESP]; Godinho, Rosely O. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Long-term use of zidovudine (AZT) may cause mitochondrial abnormalities in various tissues, including a toxic myopathy in AIDS patients associated with mitochondrial DNA (mtDNA) depletion. in the present study, we examine the short-term (48 h) effect of AZT (10, 30 and 100 mu g/ml) on the mitochondrial succinate dehydrogenase (SDH) and mtDNA content of rat cultured skeletal muscle. the effect of AZT on cytochrome c oxidase (COX) enzyme was also analyzed. the histochemical quantitative analysis of SDH showed that AZT 10, 30 and 100 mu g/ml increased by 7%, 9% and 13% the mitochondrial content. Conversely, treatment of rat cultures with 10 to 100 mu g/ml AZT reduced the mtDNA content by 23% to 66%, when compared to control values. the spontaneous contraction and the COX activity were not modified by up to 100 mu g/ml AZT. Taken together, these results show that short-term treatment with AZT can induce severe myotoxicity that involves mitochondrial proliferation and mtDNA depletion in the rat cultured myotubes. Our results also indicate that rat cultured skeletal muscle might be a valuable in vitro assay to evaluate the effect of drugs on mitochondria to predict their potential to induce mitochondrial toxicity. (C) 2007 Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosProgressive myopathy with a combined respiratory chain defect including Complex II(Elsevier B.V., 2008-01-15) Rodrigues, Andresa De Santi [UNIFESP]; Kiyomoto, Beatriz Hitomi [UNIFESP]; Oliveira, Acary Souza Bulle [UNIFESP]; Gabbai, Alberto Alain [UNIFESP]; Schmidt, Beny [UNIFESP]; Tengan, Celia Harumi [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Biochemical defects in the respiratory chain are mostly associated with deficiencies in Complexes I, III and IV, caused by nuclear or mitochondrial DNA mutations. Combined defects including Complex II have been reported very rarely and have muscular symptoms as the main manifestation, including muscle weakness, exercise intolerance and myoglobinuria. We report a patient with a fatal progressive myopathy and muscle biopsy showing diffuse reduction in succinate dehydrogenase activity, ragged red fibers and intense lipid accumulation. Cytochrome c oxidase (COX) histochemistry demonstrated 30% of fibers with increased subsarcolemmal staining while 27% were COX negative. Western blotting analysis showed reduction in the expression of the 39 kDa subunit of Complex I, subunit II of Complex IV and the 70 kDa subunit of Complex II. Our findings suggest that the patient had a complex pattern of mitochondrial dysfunction affecting multiple respiratory chain complexes (I, II and IV) and fatty acid metabolism. This report adds a new histological pattern associated to combined deficiencies of respiratory chain with involvement of Complex II and shows that this disease may be fatal with a rapid progression. (c) 2007 Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosSuccinate increases neuronal post-synaptic excitatory potentials in vitro and induces convulsive behavior through N-methyl-D-aspartate-mediated mechanisms(Elsevier B.V., 2004-01-01) Roehrs, C.; Garrido-Sanabria, E. R.; Da Silva, A. C.; Faria, L. C.; Sinhorin, VDG; Marques, R. H.; Priel, M. R.; Rubin, M. A.; Cavalheiro, E. A.; Mello, C. F.; Universidade Federal de Sergipe (UFS); Univ Texas; Universidade Federal de São Paulo (UNIFESP)Succinate is a dicarboxylic acid that accumulates due to succinate dehydrogenase inhibition by malonate and methylmalonate exposure. These neurotoxins cause increased excitability and excitotoxic damage, which can be prevented by administering high amounts of succinate. in the present study we investigated whether succinate alters hippocampal field excitatory post-synaptic potentials. Bath application of succinate at intermediate concentrations (0.31 mM) increased the slope of field excitatory post-synaptic potentials in hippocampal slices, and at high concentrations (above 1 mM) did not alter or decrease field excitatory postsynaptic potentials slope. Succinate-induced enhancement of field excitatory post-synaptic potentials slope was abolished by the addition of D-2-amino-5-phosphonovaleric acid (50 muM) to the perfusate, supporting the involvement of N-methyl-D-aspartate receptors in the excitatory effect of this organic acid. Accordingly, succinate (0.8-7.5 mumol) i.c.v. administration caused dose-dependent convulsive behavior in mice. the i.c.v. co-administration of MK-801 (7 nmol) fully prevented succinate-induced convulsions, further suggesting the involvement of N-methyl-D-aspartate receptors in the convulsant action of succinate. Our data indicate that accumulation of moderate amounts of succinate may contribute to the excitotoxicity induced by succinate dehydrogenase inhibitors, through the activation of N-methyl-D-aspartate receptors. (C) 2004 IBRO. Published by Elsevier B.V. All rights reserved.