Sulfamethoxazole induces zinc changes at hippocampal mossy fiber synapses from pregnant rats.

The accumulation of intracellular ionic zinc and pharmaceutical compounds, like the antibiotic sulfamethoxazole, may contribute to various neuropathologies. Sulfamethoxazole and the drug trimethoprim, are inhibitors of enzymes involved in the synthesis of tetrahydrofolate and also of carbonic anhydrases. The inhibition of the latter enzymes, which are localized both intra- and extracellularly and have a key role in pH regulation, causes alkalinization that is associated with higher spontaneous transmitter release. Intense synaptic stimulation causes the entry of released zinc into postsynaptic neurons, through glutamate receptor channels or voltage dependent calcium channels. The aim of this study was to evaluate the effect of sulfamethoxazole (180 µM) on basal postsynaptic zinc and to compare it with that caused by two depolarizing media, containing high potassium or tetraethylammonium, which may induce long term synaptic plasticity. The studies were performed in brain slices from gestating rats, at the mossy fiber synapses from hippocampal CA3 area, using the zinc indicator Newport Green. In the presence of KCl (20 mM) and sulfamethoxazole (180 µM) the zinc signals were enhanced, unlike in tetraethylammonium (25 mM). After sulfamethoxazole the tetraethylammonium evoked zinc signal had reduced amplitude. Thus, the data suggests that sulfamethoxazole enhances transmitter release affecting synaptic zinc physiology.

Effect of tolbutamide on tetraethylammonium-induced postsynaptic zinc signals at hippocampal mossy fiber-CA3 synapses.

The application of tetraethylammonium (TEA), a blocker of voltage-dependent potassium channels, can induce long-term potentiation (LTP) in the synaptic systems CA3-CA1 and mossy fiber-CA3 pyramidal cells of the hippocampus. In the mossy fibers, the depolarization evoked by extracellular TEA induces a large amount of glutamate and also of zinc release. It is considered that zinc has a neuromodulatory role at the mossy fiber synapses, which can, at least in part, be due to the activation of presynaptic ATP-dependent potassium (KATP) channels. The aim of this work was to study properties of TEA-induced zinc signals, detected at the mossy fiber region, using the permeant form of the zinc indicator Newport Green. The application of TEA caused a depression of those signals that was partially blocked by the KATP channel inhibitor tolbutamide. After the removal of TEA, the signals usually increased to a level above baseline. These results are in agreement with the idea that intense zinc release during strong synaptic events triggers a negative feedback action. The zinc depression, caused by the LTP-evoking chemical stimulation, turns into potentiation after TEA washout, suggesting the existence of a correspondence between the observed zinc potentiation and TEA-evoked mossy fiber LTP.

Postsynaptic zinc potentiation elicited by KCl depolarization at hippocampal mossy fiber synapses.

The hippocampal mossy fibers contain a substantial quantity of loosely-bound zinc in their glutamatergic presynaptic vesicles, which is released in synaptic transmission processes. Despite the large number of studies about this issue, the zinc changes related to short and long-term forms of potentiation are not totally understood. This work focus on zinc signals associated with chemically-induced mossy fiber synaptic plasticity, in particular on postsynaptic zinc signals evoked by KCl depolarization. The signals were detected using the medium affinity fluorescent zinc indicator Newport Green. The application of large concentrations of KCl, 20 mM and 60 mM, in the extracellular medium evoked zinc potentiations that decreased and remained stable after washout of the first and the second media, respectively. These short and long-lasting enhancements are considered to be due to zinc entry into postsynaptic neurons. We have also observed that following established zinc potentiation, another application of 60 mM KCl only elicited further enhancement when combined with external zinc. These facts support the idea that the KCl-evoked presynaptic depolarization causes higher zinc release leading to zinc influx into the postsynaptic region.

Phenolic wastewaters depuration by electrochemical oxidation process using Ti/IrO2 anodes.

The electrochemical oxidation (EO) of phenolic wastewaters mimicking olive oil mill effluents was carried out in a batch stirring reactor using Ti/IrO2 anodes, varying the nature (NaCl and Na2SO4) and electrolyte concentration (1.8-20 g L-1), current density (57-119 mA cm-2) and initial pH (3.4-9). Phenolic content (TPh) and chemical oxygen demand (COD) removals were monitored as a function of applied charge and over time. The nature of the electrolyte greatly affected the efficiency of the system, followed by the influence of the current density. The NaCl concentration and the initial pH influenced the process in a lesser extent. The best operating conditions achieved were 10 g L-1 of NaCl, current density of 119 mA cm-2 and initial pH of 3.4. These parameters led to 100 and 84.8% of TPh and COD removal, respectively. Under these conditions, some morphological differences were observed by SEM on the surface of the anode after treatment. To study the potential toxicity of the synthetic effluent in neuronal activity, this mixture was applied to rat brain slices prior to and after EO. The results indicate that although the treated effluent causes a smaller depression of the neuronal reactive oxygen species (ROS) signal than the untreated one, it leads to a potentiation instead of recovery, upon washout. Furthermore, the purification of a real olive mill wastewater (OMW), with the organic load of the synthetic effluent, using the same optimised operating conditions, achieved total phenolic compounds abatement and 62.8% of COD removal.This study demonstrates the applicability of this EO as a pre-treatment process of a real effluent, in order to achieve the legal limit values to be discharged into natural streams regarding its organic load.