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1.
Charlotte Schou Erik R. Ottosen Hans Jørgen Petersen Fredrik Björkling Scilla Latini Pernille V. Hjarnaa Erik Bramm Lise Binderup 《Bioorganic & medicinal chemistry letters》1997,7(24):616-3100
4-Pyridyl cyanoguanidines with hydrophobic aromatic side chains showed potent antiproliferative activity in the human breast and lung cancer cell lines MCF-7, NYH and H460. In vivo, treatment with N-(6-chlorophenoxyhexyl)-N′-cyano-N″-4-pyridylguanidine (18, 20 mg/kg/day po.), gave a complete remission of tumours in a model of NYH inoculated nude mice. 相似文献
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Raquel Bridi Alexandra Latini César A. Braum Giovanni K. Zorzi Moacir Wajner Eduardo Lissi 《Free radical research》2013,47(1):71-79
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 α-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 Nω-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. 相似文献
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Laura Brunelli Giuseppe Ristagno Renzo Bagnati Francesca Fumagalli Roberto Latini Roberto Fanelli Roberta Pastorelli 《Metabolomics : Official journal of the Metabolomic Society》2013,9(4):839-852
The mechanisms responsible for post-resuscitation myocardial and cerebral dysfunction are not well understood, especially in the early post-resuscitation phases. In this investigation, we first adopted unbiased mass spectrometry-based metabolomic profiling to identify perturbations in circulating metabolites in a rat model of cardiac arrest and cardiopulmonary resuscitation. Our findings strongly indicated early alterations in a major route of the tryptophan catabolism, namely the kynurenines pathway, after resuscitation. Specific metabolites involved in the tryptophan catabolism were quantified absolutely using liquid chromatography-multiple reaction monitoring-mass spectrometry. Tryptophan plasma concentration fell significantly very early in the post-resuscitation phase, while its metabolites, l-kynurenine, kynurenic acid, 3-hydroxyanthranilic acid and 5-hydroxyindoleacetic acid, rose significantly. Changes in their concentration reflected changes in rat post-resuscitation myocardial dysfunction. Elevated plasma level of kynurenic acid, 3-hydroxyanthranilic acid were associated with significant decrease in ejection fraction and stroke volume. It is well known that kynurenines pathway is involved in the pathogenesis of numerous central nervous system disorders. By implication, altered levels of tryptophan metabolites in the early post resuscitation phase might contribute to the degree of cognitive recovery. Our results suggest that kynurenine pathway is activated early following resuscitation from cardiac arrest and might account for the severity of post-resuscitation syndrome. Our explorative investigation indicate that metabolomics can help to clarify unexplored biochemical pathways in cardiopulmonary resuscitation. 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
7.
Bridi R Latini A Braum CA Zorzi GK Moacir W Lissi E Dutra-Filho CS 《Free radical research》2005,39(1):71-79
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. 相似文献
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Binderup E Björkling F Hjarnaa PV Latini S Baltzer B Carlsen M Binderup L 《Bioorganic & medicinal chemistry letters》2005,15(10):2491-2494
To overcome pharmacokinetic and solubility problems observed in early clinical trials with the potent anticancer compound CHS828, we synthesised a series of prodrugs with improved properties. The best compound obtained was EB1627, with a tetraethyleneglycol moiety attached to the parent drug via a carbonate linkage. This compound was found soluble enough to be given i.v. and the drug was rapidly released in vivo exerting a very potent inhibitory activity alone and in combination with known cytostatics (etoposide) in animal models in vivo. 相似文献
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Rotenone calibration of fish density and biomass in a tropical stream sampled by two removal methods
A catch-depletion method was applied using two sampling gears in three sites of a small tributary of the Corumba River (Goiás State, Brazil) in two seasons. The gears were: a double stick net (DSN) in one site and electric fishing (EF) in two sites. The calibration of both gears was performed using rotenone. EF was almost sufficient to establish a complete local species list, but DSN was not. Underestimation of calculated density (N) and biomass (B) values for DSN and EF amounted to 62 and 29%, respectively. The results of N and B obtained by EF were too imprecise to calculate secondary fish production to be applied in a field bioenergetics model. We could not conclusively prove that mean body weight of sampled populations was significantly lower for fish caught by EF, although all of these means were higher for fish collected by rotenone, at each site and on two sampling occasions. 相似文献