N-acetylcysteine and ceftriaxone as preconditioning strategies in focal brain ischemia : influence on glutamate transporters expression

Glutamate (Glu) plays a key role in excitotoxicity-related injury in cerebral ischemia. In the brain, Glu homeostasis depends on Glu transporters, including the excitatory amino acid transporters and the cysteine/Glu antiporter (xc-). We hypothesized that drugs acting on Glu transporters, such as ceftriaxone (CEF, 200 mg/kg, i.p.) and N-acetylcysteine (NAC, 150 mg/kg, i.p.), administered repeatedly for 5 days before focal cerebral ischemia in rats and induced by a 90-min middle cerebral artery occlusion (MCAO), may induce brain tolerance to ischemia. We compared the effects of these drugs on brain infarct volume, neurological deficits and the mRNA and protein expression of the Glu transporter-1 (GLT-1) and xc- with the effects of ischemic preconditioning and chemical preconditioning using 3-nitropropionic acid. Administration of CEF and NAC significantly reduced infarct size and neurological deficits caused by a 90-min MCAO. These beneficial effects were accompanied by changes in GLT-1 expression caused by a 90-min MCAO at both the mRNA and protein levels in the frontal cortex, hippocampus, and dorsal striatum. Thus, the results of this study suggest that the regulation of GLT-1 and xc- plays a role in the development of cerebral tolerance to ischemia and that this regulation may be a novel approach in the therapy of brain ischemia

The effects of 2-methoxyethanol and 2-ethoxyethanol on hematological changes induced by 2-butoxyethanol

Background: Alkoxyethanols (ethylene glycol alkyl ethers) are used as mixtures in a variety of industrial and household products. The aim of this study has been to evaluate the effects of 2-methoxyethanol (ME) and 2-ethoxyethanol (EE) on hematological changes induced by 2-butoxyethanol (BE) in rats. Material and Methods: Experiments were performed on male Wistar rats treated subcutaneously with BE, ME, and EE alone (in the dose of 0.75 mM/kg/day and 1.25 mM/kg/day) and their mixtures with the molar ratio 1:1, for 4 weeks. Hematological analyses were performed on the day 0, 4, 11, 18, and 29. Hemoglobin (HGB) concentration in the urine was also determined in the rats treated with BE alone and co-exposed to BE and ME and also BE and EE. Results: The rats co-exposed to BE and ME or BE and EE demonstrated significantly less pronounced hematological changes in comparison with animals treated with BE alone at the beginning of exposure. At the later period the hematological alterations in the same animals were markedly pronounced and progressing with exposure time. The rats co-exposed to BE and ME or BE and EE did not demonstrate hemoglobinuria. Conclusions: ME or EE co-administered to rats with BE lead to the amelioration in the majority of the hematological parameters at the beginning of the exposure. The hematological changes at the end of the co-exposure to BE and ME or BE and EE were markedly pronounced. The effects observed in this study appear to be related with metabolic interactions of the examined ether. Med Pr 2015;66(3):303–31

Ethylene glycol ethers induce oxidative stress in the rat brain

Ethylene glycol ethers (EGEs) are components of many industrial and household products. Their hemolytic and gonadotoxic effects are relatively well known while their potential adverse effects on the central nervous system have not yet been clearly demonstrated. The aim of the present study was to examine the effects of 4-week administration of 2-buthoxyethanol (BE), 2-phenoxyethanol (PHE) and 2-ethoxyethanol (EE) on the total antioxidant capacity, activity of some antioxidant enzymes, such as the superoxide dismutase (SOD), catalase, glutathione peroxidase (GPX) and glutathione reductase and lipid peroxidation in the frontal cortex and hippocampus in the rat. These studies showed that BE and PHE decreased the total antioxidant activity, SOD and GPX activity, while increased lipid peroxidation in the frontal cortex. Like in the frontal cortex, also in the hippocampus BE and PHE attenuated the total antioxidant activity, however, lipid peroxidation was increased only in animals which received BE while reduction in GPX activity was present in rats administered PHE. The obtained data indicated that 4-week administration of BE and PHE, but not EE, reduced the total antioxidant activity and enhanced lipid peroxidation in the brain. In the frontal cortex, adverse effects of PHE and BE on lipid peroxidation probably depended on reduction in SOD and GPX activity, however, in the hippocampus the changes in the total antioxidant activity and lipid peroxidation were not connected with reduction of the investigated antioxidant enzyme activity

The effect of chronic tianeptine administration on the brain mitochondria : direct links with an animal model of depression

A growing body of evidence has focused on the impact of mitochondrial disturbances in the development of depression, but little data exist regarding the effects of chronic administration of antidepressant drugs on the brain’s mitochondrial protein profile. The aim of this study was to investigate the impact of chronic treatment with an atypical antidepressant drug—tianeptine—on the mitochondria-enriched subproteome profile in the hippocampus and the frontal cortex of 3-month-old male rats following a prenatal stress procedure. Rats that were exposed to a prenatal stress procedure displayed depressive- and anxiety-like disturbances based on the elevated plus-maze and Porsolt tests. Moreover, two-dimensional electrophoresis coupled with mass spectrometry showed structure-dependent mitoproteome changes in brains of prenatally stressed rats after chronic tianeptine administration. A component of 2-oxoglutarate and succinate flavoprotein subunit dehydrogenases, isocitrate subunit alpha, was upregulated in the hippocampus. In the frontal cortex, there was a striking increase in the expression of glutamate dehydrogenase and cytochrome bc1 complex subunit 2. These findings suggest that mitochondria are underappreciated targets for therapeutic interventions, and mitochondrial function may be crucial for the effective treatment of stress-related diseases

Preliminary study on Se-enriched Lentinula edodes mycelium as a proposal of new feed additive in selenium deficiency

The presence of selenium in European soil is low and this causes its deficiency in livestock and, in consequence, in humans. This study aimed to obtain Lentinula (L.) edodes mycelium with the maximum content of selenium. This species was used for experiment based on its documented medicinal properties. Calves were fed with selenium-enriched L. edodes mycelium, and serum selenium concentration, average daily weight gains and selected immune parameters were estimated. The selenium-enriched mushroom was found to be safe based on cytotoxicity tests (MTT and LDH tests) and for this reason it was used for further experiments. The mean quantity of selenium in the serum of calves fed with selenium-enriched L. edodes mycelium was significantly higher than that of control calves. Additionally, the calves fed with selenium-enriched L. edodes mycelium had higher body weight gains than those of control calves. White blood cell counts and subpopulations of lymphocytes in the experimental and control calves were within the reference range. The administration of L. edodes enriched with selenium had a beneficial effect on state of health of the calves

Effects of Cocaine-Kindling on the Expression of NMDA Receptors and Glutamate Levels in Mouse Brain

In the present study we examined the effects of cocaine seizure kindling on the expression of NMDA receptors and levels of extracellular glutamate in mouse brain. Quantitative autoradiography did not reveal any changes in binding of [3H] MK-801 to NMDA receptors in several brain regions. Likewise, in situ hybridization and Western blotting revealed no alteration in expression of the NMDA receptor subunits, NR1 and NR2B. Basal overflow of glutamate in the ventral hippocampus determined by microdialysis in freely moving animals also did not differ between cocaine-kindled and control groups. Perfusion with the selective excitatory amino acid transporter inhibitor, pyrrolidine-2,4-dicarboxylic acid (tPDC, 0.6 mM), increased glutamate overflow confirming transport inhibition. Importantly, KCl-evoked glutamate overflow under tPDC perfusion was significantly higher in cocaine-kindled mice than in control mice. These data suggest that enhancement of depolarization stimulated glutamate release may be one of the mechanisms underlying the development of increased seizure susceptibility after cocaine kindling