排序方式: 共有15条查询结果,搜索用时 31 毫秒
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Seminotti Bianca Roginski Ana Cristina Zanatta Ângela Amaral Alexandre Umpierrez Fernandes Thabata Spannenberger Kaleb Pinto da Silva Lucas Henrique Rodrigues Ribeiro Rafael Teixeira Leipnitz Guilhian Wajner Moacir 《Journal of bioenergetics and biomembranes》2021,53(5):525-539
Journal of Bioenergetics and Biomembranes - S-adenosylmethionine (AdoMet) predominantly accumulates in tissues and biological fluids of patients affected by liver dysmethylating diseases,... 相似文献
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Carolina G. Fernandes Guilhian Leipnitz Bianca Seminotti Alexandre U. Amaral Ângela Zanatta Carmen R. Vargas Carlos S. Dutra Filho Moacir Wajner 《Cellular and molecular neurobiology》2010,30(2):317-326
High levels of phenylalanine (Phe) are the biochemical hallmark of phenylketonuria (PKU), a neurometabolic disorder clinically
characterized by severe mental retardation and other brain abnormalities, including cortical atrophy and microcephaly. Considering
that the pathomechanisms leading to brain damage and particularly the marked cognitive impairment in this disease are poorly
understood, in the present study we investigated the in vitro effect of Phe, at similar concentrations as to those found in
brain of PKU patients, on important parameters of oxidative stress in the hippocampus and cerebral cortex of developing rats.
We found that Phe induced in vitro lipid peroxidation (increase of TBA-RS values) and protein oxidative damage (sulfhydryl
oxidation) in both cerebral structures. Furthermore, these effects were probably mediated by reactive oxygen species, since
the lipid oxidative damage was totally prevented by the free radical scavengers α-tocopherol and melatonin, but not by L-NAME,
a potent inhibitor of nitric oxide synthase. Accordingly, Phe did not induce nitric oxide synthesis, but significantly decreased
the levels of reduced glutathione (GSH), the major brain antioxidant defense, in hippocampus and cerebral cortex supernatants.
Phe also reduced the thiol groups of a commercial GSH solution in a cell-free medium. We also found that the major metabolites
of Phe catabolism, phenylpyruvate, phenyllactate and phenylacetate also increased TBA-RS levels in cerebral cortex, but to
a lesser degree. The data indicate that Phe elicits oxidative stress in the hippocampus, a structure mainly involved with
learning/memory, and also in the cerebral cortex, which is severely damaged in PKU patients. It is therefore presumed that
this pathomechanism may be involved at least in part in the severe cognitive deficit and in the characteristic cortical atrophy
associated with dysmyelination and leukodystrophy observed in this disorder. 相似文献
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Mateus Struecker da Rosa Bianca Seminotti César Augusto João Ribeiro Belisa Parmeggiani Mateus Grings Moacir Wajner 《Free radical research》2016,50(9):997-1010
3-Hydroxy-3-methylglutaryl-coenzyme A lyase (HL) deficiency is characterized by tissue accumulation of 3-hydroxy-3-methylglutaric (HMG), and 3-methylglutaric (MGA) acids. Affected patients present cardiomyopathy, whose pathomechanisms are not yet established. We investigated the effects of HMG and MGA on energy and redox homeostasis in rat heart using in vivo and in vitro models. In vivo experiments showed that intraperitoneal administration of HMG and MGA decreased the activities of the respiratory chain complex II and creatine kinase (CK), whereas HMG also decreased the activity of complex II–III. Furthermore, HMG and MGA injection increased reactive species production and carbonyl formation, and decreased glutathione concentrations. Regarding the enzymatic antioxidant defenses, HMG and MGA increased glutathione peroxidase (GPx) and glutathione reductase (GR) activities, while only MGA diminished the activities of superoxide dismutase (SOD) and catalase, as well as the protein content of SOD1. Pre-treatment with melatonin (MEL) prevented MGA-induced decrease of CK activity and SOD1 levels. In vitro results demonstrated that HMG and MGA increased reactive species formation, induced lipid peroxidation and decreased glutathione. We also verified that reactive species overproduction and glutathione decrease provoked by HMG and MGA were abrogated by MEL and lipoic acid (LA), while only MEL prevented HMG- and MGA-induced lipoperoxidation. Allopurinol (ALP) also prevented reactive species overproduction caused by both metabolites. Our data provide solid evidence that bioenergetics dysfunction and oxidative stress are induced by HMG and MGA in heart, which may explain the cardiac dysfunction observed in HL deficiency, and also suggest that antioxidant supplementation could be considered as adjuvant therapy for affected patients. 相似文献
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Solano AF Leipnitz G De Bortoli GM Seminotti B Amaral AU Fernandes CG Latini AS Dutra-Filho CS Wajner M 《Free radical research》2008,42(8):707-715
The present work investigated the in vitro effects of isovaleric acid (IVA) and isovalerylglycine (IVG), which accumulate in isovaleric acidemia (IVAcidemia), on important parameters of oxidative stress in supernatants and mitochondrial preparations from brain of 30-day-old rats. IVG, but not IVA, significantly increased TBA-RS and chemiluminescence values in cortical supernatants. Furthermore, the addition of free radical scavengers fully prevented IVG-induced increase of TBA-RS. IVG also decreased GSH concentrations, whereas IVA did not modify this parameter in brain supernatants. Furthermore, IVG did not alter lipid peroxidation or GSH concentrations in mitochondrial preparations, indicating that the generation of oxidants by IVG was dependent on cytosolic mechanisms. On the other hand, IVA significantly induced carbonyl formation both in supernatants and purified mitochondrial preparations from rat brain, with no effect observed for IVG. Therefore, it is presumed that oxidative damage may be at least in part involved in the pathophysiology of the neuropathology of IVAcidemia. 相似文献
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Seminotti B Fernandes CG Leipnitz G Amaral AU Zanatta A Wajner M 《Neurochemical research》2011,36(2):205-214
Lysine (Lys) accumulation in tissues and biological fluids is the biochemical hallmark of patients affected by familial hyperlysinemia
(FH) and other inherited metabolic disorders. In the present study we investigated the effects of acute administration of
Lys on relevant parameters of energy metabolism and oxidative stress in striatum of young rats. We verified that Lys in vivo
intrastriatal injection did not change the citric acid cycle function and creatine kinase activity, but, in contrast, significantly
inhibited synaptic Na+,K+-ATPase activity in striatum prepared 2 and 12 h after injection. Moreover, Lys induced lipid peroxidation and diminished
the concentrations of glutathione 2 h after injection. These effects were prevented by the antioxidant scavengers melatonin
and the combination of α-tocopherol and ascorbic acid. Lys also inhibited glutathione peroxidase activity 12 h after injection.
Therefore it is assumed that inhibition of synaptic Na+,K+-ATPase and oxidative damage caused by brain Lys accumulation may possibly contribute to the neurological manifestations of
FH and other neurometabolic conditions with high concentrations of this amino acid. 相似文献
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Ana Laura Colín-González Ariana Lizbeth Paz-Loyola María Eduarda de Lima Sonia Galván-Arzate Bianca Seminotti César Augusto João Ribeiro Guilhian Leipnitz Diogo Onofre Souza Moacir Wajner Abel Santamaría 《Neurochemical research》2016,41(10):2619-2626
3-Methylglutaric acid (3MGA) is an organic acid that accumulates in various organic acidemias whose patients present neurodegeneration events in children coursing with metabolic acidurias. Limited evidence describes the toxic mechanisms elicited by 3MGA in the brain. Herein, we explored the effects of 3MGA on different toxic endpoints in synaptosomal and mitochondrial-enriched fractions of adult rat brains to provide novel information on early mechanisms evoked by this metabolite. At 1 and 5 mM concentration, 3MGA increased lipid peroxidation, but decreased mitochondrial function only at 5 mM concentration. Despite less intense effects were obtained at 1 mM concentration, its co-administration with the kynurenine pathway (KP) metabolite and N-methyl-d-aspartate receptor (NMDAr) agonist, quinolinic acid (QUIN, 50 and 100 µM), produced toxic synergism on markers of oxidative stress and mitochondrial function. The toxicity of 3MGA per se (5 mM) was prevented by the cannabinoid receptor agonist WIN55,212-2 and the NMDAr antagonist kynurenic acid (KYNA), suggesting cannabinoid and glutamatergic components in the 3MGA pattern of toxicity. The synergic model (3MGA?+?QUIN) was also sensitive to KYNA and the antioxidant S-allylcysteine, but not to the nitric oxide synthase inhibitor l-nitroarginine methyl ester. These findings suggest various underlying mechanisms involved in the neurotoxicity of 3MGA that may possibly contribute to the neurodegeneration observed in acidemias. 相似文献
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Fernandes CG Borges CG Seminotti B Amaral AU Knebel LA Eichler P de Oliveira AB Leipnitz G Wajner M 《Cellular and molecular neurobiology》2011,31(5):775-785
Methylmalonic acidemia and propionic acidemia are organic acidemias biochemically characterized by predominant tissue accumulation
of methylmalonic acid (MMA) and propionic acid (PA), respectively. Affected patients present predominantly neurological symptoms,
whose pathogenesis is not yet fully established. In the present study we investigated the in vitro effects of MMA and PA on
important parameters of lipid and protein oxidative damage and on the production of reactive species in synaptosomes from
cerebrum of developing rats. Synaptosomes correspond to nerve terminals that have been used to investigate toxic properties
of compounds on neuronal cells. The in vivo effects of intrastriatal injection of MMA and PA on the same parameters and on
enzymatic antioxidant defenses, were also studied. MMA-induced in vitro and in vivo lipid peroxidation and protein oxidative
damage. Furthermore, the lipid oxidative damage was attenuated or prevented, pending on the doses utilized, by the free radical
scavengers α-tocopherol, melatonin and by the NMDA glutamate receptor antagonist MK-801, implying the involvement of reactive
species and glutamate receptor activation in these effects. In addition, 2′,7′-dichlorofluorescein diacetate oxidation was
significantly increased in synaptosomes by MMA, reinforcing that reactive species generation is elicited by this organic acid.
We also verified that glutathione peroxidase activity was inhibited by intrastriatal MMA injection. In contrast, PA did not
induce any significant effect on all parameters examined in vitro and in vivo, implying a selective action for MMA. The present
data demonstrate that oxidative stress is induced by MMA in vitro in nerve terminals and in vivo in striatum, suggesting the
participation of neuronal cells in MMA-elicited oxidative damage. 相似文献
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Leipnitz G Seminotti B Amaral AU de Bortoli G Solano A Schuck PF Wyse AT Wannmacher CM Latini A Wajner M 《Life sciences》2008,82(11-12):652-662
3-methylglutaconic (MGT), 3-methylglutaric (MGA) and occasionally 3-hydroxyisovaleric (OHIVA) acids accumulate in a group of diseases known as 3-methylglutaconic aciduria (MGTA). Although the clinical presentation of MGTA is mainly characterized by neurological symptoms, the mechanisms of brain damage in this disease are poorly known. In the present study we investigated the in vitro effect of MGT, MGA and OHIVA on various parameters of oxidative stress in cerebral cortex from young rats. Thiobarbituric acid-reactive substances (TBA-RS) and chemiluminescence were significantly increased by MGT, MGA and OHIVA, indicating that these metabolites induce lipid oxidative damage. Furthermore, the addition of melatonin, alpha-tocopherol and superoxide dismutase plus catalase fully prevented MGT-induced increase on TBA-RS, suggesting that free radicals were involved in this effect. These metabolites also provoked protein oxidative damage determined by increased carbonyl formation and sulfhydryl oxidation, but did not induce superoxide generation in submitochondrial particles. It was also verified that MGA and MGT significantly decreased the non-enzymatic antioxidant defenses in cerebral cortex supernatants and that melatonin and alpha-tocopherol totally blocked MGA-induced GSH reduction. The data indicate that the metabolites accumulating in MGTA elicit oxidative stress in vitro in the cerebral cortex. It is therefore presumed that this pathomechanism may be involved in the brain damage observed in patients affected by MGTA. 相似文献
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Francielle BückerNaiara Aguiar Santestevan Luiz Fernando RoeschRodrigo J. Seminotti Jacques Maria do Carmo Ruaro PeralbaFlávio Anastácio de Oliveira Camargo Fátima Menezes Bento 《International biodeterioration & biodegradation》2011,65(1):172-178
Alternative fuels are receiving considerable attention, especially biodiesel, which is recognized for its environmental benefits. One advantage is its biodegradability. However, biodegradability may allow the fuel to be more susceptible to microbial contamination, especially during storage. The susceptibility to biodeterioration of biodiesel, diesel, and diesel containing 5, 10, and 20% biodiesel was evaluated using fungi isolated from contaminated oil systems. Paecilomyces sp. produced the highest biomass in 20% and 100% biodiesel, while Aspergillus fumigatus grew best in pure biodiesel. Yeasts had the highest rates of degradation, especially Candida silvicola, with 100% degradation of all esters. Rhodotorula sp. showed greatest activity for C18:3 (linolenic acid), at 39.4%, followed by C18:1 (oleic acid) and C16 (palmitic acid), at 21% and 15%, respectively, after 7 days of incubation. The results are relevant for the resolution of the decade-long debate on the increase in diesel biodegradability due to the addition of biodiesel. 相似文献