Biological effects of a copper-based fungicide on the fruit fly, Drosophila melanogaster.

The increased consumption of pesticides can have a negative environmental impact by increasing the essential metals to toxic levels. Bordasul® is a commonly used fungicide in Brazil and it is composed of 20% Cu, 10% sulfur, and 3.0% calcium. The study of fungicides in vivo in non-target model organisms can predict their environmental impact more broadly. The Drosophila melanogaster is a unique model due to its ease of handling and maintenance. Here, the potential toxicity of Bordasul® was investigated by assessing the development, survival, and behavior of exposed flies. Exposure to Bordasul® impaired the development (p < 0.01) and caused a significant reduction in memory retention (p < 0.05) and locomotor ability (p < 0.001). Fungicides are needed to assure the world's food demand; however, Bordasul® was highly toxic to D. melanogaster. Therefore, Bordasul® may be potentially toxic to non-target invertebrates and new environmentally-safe biofertilizers have to be developed to preserve the biota.

6-Gingerol-rich fraction from Zingiber officinale ameliorates carbendazim-induced endocrine disruption and toxicity in testes and epididymis of rats.

This study evaluated the protective effects of 6-gingerol-rich fraction (6-GRF) from Zingiber officinale on carbendazim (CBZ)-induced reproductive toxicity in rats. Adult male rats were treated with either CBZ (50 mg/kg) alone or in combination with 6-GRF (50, 100 and 200 mg/kg) for 14 consecutive days. Gas chromatography-mass spectrometry (GCMS) analysis revealed that 6-GRF consists of ten bioactive chemical components with 6-gingerol being the most abundant (30.76%). Administration of 6-GRF significantly (p < .05) prevented CBZ-mediated increase in absolute and relative testes weights as well as restored the sperm quantity and quality in the treated rats to near control. In testes and epididymis, 6-GRF significantly abolished CBZ-mediated increase in oxidative damage as well as augmented antioxidant enzymes activities and glutathione level in the treated rats. Moreover, CBZ administration alone significantly decreased plasma levels of testosterone, thyrotropin, triiodothyronine and tetraiodothyronine, whereas follicle-stimulating hormone was significantly elevated without affecting luteinising hormone and prolactin levels when compared with the control. Conversely, 6-GRF ameliorated the disruption in the hormonal levels and restored their levels to near normalcy in CBZ-treated rats. Collectively, 6-GRF inhibited the adverse effects of CBZ on the antioxidant defence systems, hormonal balance and histology of the testes and epididymis in rats.

Effects of Hg(II) exposure on MAPK phosphorylation and antioxidant system in D. melanogaster.

The heavy metal mercury is a known toxin, but while the mechanisms involved in mercury toxicity have been well demonstrated in vertebrates, little is known about toxicological effects of this metal in invertebrates. Here, we present the results of our study investigating the effects associated with exposure of fruit fly Drosophila melanogaster to inorganic mercury (HgCl2 ). We quantify survival and locomotor performance as well as a variety of biochemical parameters including antioxidant status, MAPK phosphorylation and gene expression following mercury treatment. Our results demonstrate that exposure to Hg(II) through diet induced mortality and affected locomotor performance as evaluated by negative geotaxis, in D. melanogaster. We also saw a significant impact on the antioxidant system including an inhibition of acetylcholinesterase (Ache), glutathione S-transferase (GST) and superoxide dismutase (SOD) activities. We found no significant alteration in the levels of mRNA of antioxidant enzymes or NRF-2 transcriptional factor, but did detect a significant up regulation of the HSP83 gene. Mercury exposure also induced the phosphorylation of JNK and ERK, without altering p38(MAPK) and the concentration of these kinases. In parallel, Hg(II) induced PARP cleavage in a 89 kDa fragment, suggesting the triggering of apoptotic cell death in response to the treatment. Taken together, this data clarifies and extends our understanding of the molecular mechanisms mediating Hg(II) toxicity in an invertebrate model.

Interplay between diphenyl diselenide and copper: Impact on D. melanogaster survival, behavior, and biochemical parameters.

Copper (Cu2+) is a biologically essential element that participates in numerous physiological processes. However, elevated concentrations of copper have been associated with cellular oxidative stress and neurodegenerative diseases. Organo­selenium compounds such as diphenyl diselenide (DPDS) have in vitro and in vivo antioxidant properties. Hence, we hypothesized that DPDS may modulate the toxicity of Cu2+ in Drosophila melanogaster. The acute effects (4 days of exposure) caused by a high concentration of Cu2+ (3 mM) were studied using endpoints of toxicity such as survival and behavior in D. melanogaster. The potential protective effect of low concentration of DPDS (20 µM) against Cu2+ was also investigated. Adult flies aged 1-5 days post-eclosion (both sexes) were divided into four groups: Control, DPDS (20 µM), CuSO4 (3 mM), and the combined exposure of DPDS (20 µM) and CuSO4 (3 mM). Survival, biochemical, and behavioral parameters were determined. Co-exposure of DPDS and CuSO4 increased acetylcholinesterase (AChE) activity and the generation of reactive oxygen species (ROS as determined by DFCH oxidation). Contrary to our expectation, the co-exposure reduced survival, body weight, locomotion, catalase activity, and cell viability in relation to control group. Taken together, DPDS potentiated the Cu2+ toxicity.

Gallic acid modulates cerebral oxidative stress conditions and activities of enzyme-dependent signaling systems in streptozotocin-treated rats.

Redox imbalances and altered signaling processes in the brain are characteristic features of diabetic complications. Hence, the present study therefore sought to evaluate the effect of gallic acid (GA) on disturbed redox systems and activity of neurotransmission signaling dependent enzymes such as sodium pump, purinergic enzymes and acetylcholinesterase in diabetic animal models. We observed that GA markedly improves the antioxidant status of diabetic animals. Furthermore, the diminution of the activity of Na(+)/K(+)-ATPase and increased activities of acetylcholinesterase and the purinergic enzymes associated with diabetes progression were reversed to normalcy with the administration of GA in diabetic animals. Hence, we conclude that GA is a potential candidate in the management of neuronal dysfunction that often accompanied complications associated with diabetic hyperglycemia.

Irrigation of Solanum lycopersicum L. with magnetically treated water increases antioxidant properties of its tomato fruits.

Antioxidant effects of tomatoes (Solanum lycopersicum L.) have been studied and an association between dietary intake of tomatoes and lowered risk of cancer, neurodegenerative, and cardiovascular diseases has been suggested. Here we used magnetically treated water (MTW; 0.03-0.15 T), which promotes better germination and productivity in tomatoes, and we investigated the effects of aqueous and ethanolic (10-400 µg/ml) extracts of S. lycopersicum as potential antioxidant against 10 µM Fe(II)-induced thiobarbituric acid reactive species (TBARS) in liver and brain homogenates from rats. The ethanolic extracts from magnetically treated plants were more effective than aqueous extracts in preventing TBARS formation in brain and liver. The protective effects of ethanolic extract can be associated with antioxidants (polyphenols and flavonoids), lycopene and other lipophilic components found in the extract. In effect, magnetically treated plants had higher content of polyphenolic and flavonoid compounds than nontreated plants and they can be a better source of antioxidants than nontreated plants. Consequently, MTW can be used to produce functional foods with high contents of antioxidant components and may have better beneficial health effects than traditionally produced foods.

Toxicological and behavioral analyses indicates the safety of a biofertilizer in the non-target D. melanogaster.

The demand for food to feed the growing world population has been promoting the indiscriminate use of chemical fertilizers, which can be detrimental to the environment. In order to maintain high crop productivity without damaging the ecosystem, biofertilizers have emerged as alternative to reduce the use of chemical fertilizers. So, environmentally safer biofertilizer can replace the exploitation of more toxic chemical fertilizer. Here, the fly Drosophila melanogaster was used to study the potential toxicity of the biofertilizer Beifort®. Flies were exposed to high concentrations of Beifort® in the diet (1.8 mL/L, 9.0 mL/L and 18 mL/L), and morphological and behavioral endpoints of toxicity were analyzed (development from egg to adult age, flies longevity, climbing performance, memory and learning of an associative learning, larvae digestive tract damage and plasmid DNA break). Beifort® did not modify flies development, survival, digestive track cell damage, locomotor activity or memory. Beifort® did not induce DNA breakage in vitro and had no toxicity to the non-target D. melanogaster after in vivo exposure. Thus, in addition of promoting the sustainable use of agricultural wastes, the exploitation of Beifort® can contribute to decrease the use of chemical fertilizers.

Molecular docking studies of disubstituted diaryl diselenides as mammalian δ-aminolevulinic acid dehydratase enzyme inhibitors.

δ-Aminolevulinic acid dehydratase (δ-ALAD) is a metalloprotein that catalyzes porphobilinogen formation. This enzyme is sensitive to pro-oxidants and classically used as a biomarker of lead (Pb) intoxication. Diphenyl diselenide [(PhSe)2] and analogs bis(4-chlorophenyl) diselenide [(pCl3PhSe)2], bis(4-methoxyphenyl)diselenide [(pCH3OPhSe)2], and bis[3-(trifluoromethy)phenyl] diselenide [(mCF3PhSe)2] inhibit mammalian δ-ALAD by oxidizing enzyme cysteinyl residues, which are involved in diselenide-induced toxicity. 2-Cysteinyl residues from δ-ALAD are believed to sequentially interact with (PhSe)2. Thus this study utilized protein-ligand docking analyses to determine which cysteinyl residues might be involved in the inhibitory effect of (PhSe)2 and analogs toward δ-ALAD. All diselenides that interact in a similar manner with the active site of δ-ALAD were examined. Docking simulations indicated an important role for π-π interactions involving Phe208 and cation-π interactions involving Lys199 and Arg209 residues with the aromatic ring of (PhSe)2 and analogs. Based upon these interactions an approximation between Se atoms and -SH of Cys124, with distances ranging between 3.3 Å and 3.5 Å, was obtained. These data support our previous postulations regarding the mechanism underlying δ-ALAD oxidation mediated by (PhSe)2 and analogs. Based on protein-ligand docking analyses, data indicated that -SH of Cys124 attacks one of the Se atoms of -SH of (PhSe)2 releasing one PhSeH (selenophenol). Subsequently, the -SH of Cys132 attacks the sulfur atom of Cys124 (from the bond of E-S-Se-Ph indermediate), generating the second PhSe⁻, and the oxidized and inhibited δ-ALAD. In conclusion, AutoDock Vina 1.1.1 was a useful tool to search for diselenides inhibitors of δ-ALAD, and, most importantly, it provided insight into molecular mechanisms involved in enzyme inhibition.

Comparative study on the influence of subcutaneous administration of diphenyl and dicholesteroyl diselenides on sulphydryl proteins and antioxidant parameters in mice.

Although in vitro data from our previous studies show that the antioxidant effect and reactions of both diphenyl diselenide (DPDS) and dicholesteroyl diselenide (DCDS) towards thiol-containing proteins differ considerably, the present study sought to evaluate the interaction of both organodiselenides with thiol-containing proteins in vivo. Mice were injected subcutaneously with DPDS or DCDS previously dissolved in soya bean oil at doses of 0.5 mmol kg⁻¹ body weight for four consecutive days. The activities of delta aminolevulinic acid dehydratase (ALA-D), Na+/K+-ATPase, and isoforms of lactate dehydrogenase (LDH) and catalase were investigated. In addition, the antioxidant status of the mice was determined by measuring the levels of glutathione (GSH), vitamin C (Vit C) and thiobarbituric acid reactive substances. The results show that both diselenides significantly increased the levels of GSH and Vit C but did not markedly alter other antioxidant indices. With respect to the thiol-containing enzymes that were evaluated, DPDS and not DCDS caused a marked reduction in the activities of hepatic ALA-D; however, both diselenides inhibited all isoforms of LDH evaluated. In addition, the activities of cerebral Na+/K+-ATPase were not markedly inhibited by both diselenides, suggesting that this cerebral enzyme may not be a molecular target of organodiselenides toxicity. Taken together, the pharmacological and toxicological chemistry of organoselenium compounds is complex and multifactorial and is dependent on delicate equations which include vehicle solution, animal species and mode of delivery.

Copper decreases associative learning and memory in Drosophila melanogaster.

Copper is an essential element to all living organisms. Repeated use of metal-enriched chemicals, fertilizers, and organic substances may cause contamination at a large scale. Altered levels of Cu2+ may result in harmful effects and can be associated with memory and cognitive dysfunction. Studying simple, genetically tractable organisms such as Drosophila melanogaster, can reveal important data on the neural basis of conditioning. D. melanogaster is an important alternative experimental model to assess the toxic response to metals. In the present study, the effects of copper on flies' development and in learning and memory retention in male and female adult flies were investigated. We paired an odorant to pain perception and observed the aversion behavior over time. Exposure of D. melanogaster eggs to Cu2+ increased mortality of larvae, pupae, and adults and decreased memory retention in adults. Moreover, male flies demonstrated to be more susceptible to Cu2+ toxicity than females. The results therefore, reinforce the importance of controlling the anthropogenic heavy-metals soil contamination given their hazardous effects to living organisms.

Importance of schedule of administration in the therapeutic efficacy of guanosine: early intervention after injury enhances glutamate uptake in model of hypoxia-ischemia.

Perinatal cerebral hypoxia-ischemia (HI) is an important cause of mortality and neurological disabilities such as cerebral palsy, epilepsy, and mental retardation. The potential for neuroprotection in HI can be achieved mainly during the recovery period. In previous work, we demonstrated that guanosine (Guo) prevented the decrease of glutamate uptake by hippocampal slices of neonatal rats exposed to a hypoxic-ischemic (HI) insult in vivo when administrated before and after insult. In the present study, we compared the effect of Guo administration only after HI using various protocols. When compared with the control, a decrease of [(3)H] glutamate uptake was avoided only when three doses of Guo were administered immediately, 24 h and 48 h after insult, or at 3 h, 24 h, and 48 h after injury or at 6 h, 24 h, and 48 h after HI. These findings indicate that early Guo administration (until 6 h) after HI, in three doses may enhance glutamate uptake into brain slices after hypoxia/ischemia, probably resulting in decreased excitotoxicity.

Effect of oral administration of diphenyl diselenide on antioxidant status, and activity of delta aminolevulinic acid dehydratase and isoforms of lactate dehydrogenase, in streptozotocin-induced diabetic rats.

Male albino rats with diabetes induced by the administration of streptozotocin (STZ) (45 mg/kg, i.v.) were treated with oral administration of diphenyl diselenide (DPDS) pre-dissolved in soya bean oil. A significant reduction in blood glucose levels was observed in STZ-induced diabetic rats treated with DPDS compared with an untreated STZ diabetic group. The pharmacological effect of DPDS was accompanied by a marked reduction in the level of glycated proteins, and restoration of the observed decreased levels of vitamin C and reduced glutathione (GSH; in liver and kidney tissues) of STZ-treated rats. DPDS also caused a marked reduction in the high levels of thiobarbituric acid reactive substances (TBARS) observed in STZ-induced diabetic group. Finally, the inhibition of catalase, delta aminolevulinic acid dehydratase (eth-ALA-D) and isoforms of lactate dehydrogenase (LDH) accompanied by hyperglycemia were prevented by DPDS in all tissues examined. Hence, in comparison with our earlier report, the present findings suggests that, irrespective of the route of administration and the delivery vehicle, DPDS can be considered as an anti-diabetic agent due to its anti-hyperglycemic and antioxidant properties.

Genotoxicity of organoselenium compounds in human leukocytes in vitro.

DNA damage and cell viability of human leukocytes cells were examined as simple tests for screening the potential toxicity of organoselenium compounds. Leukocytes were incubated with different organoselenium compounds at 4, 10, 40 and 100 microM or vehicle (DMSO) for 3h at 37 degrees C before of in vitro assays. Cell viability was determined by Trypan blue exclusion. DNA damage was assessed using the alkaline comet assay with silver staining. The exposure of leukocytes to (S)-tert-butyl 1-diselenide-3-methylbutan-2-ylcarbamate, (S)-tert-butyl 1-diselenide-3-phenylpropan-2-ylcarbamate, (S)-2-amino-1-diselenide-3-methylpropanyl, (S)-2-amino-1-diselenide-3-phenylpropanyl, 3',3-ditrifluoromethyl diphenyl diselenide, 4',4-dimethoxy diphenyl diselenide, 4',4-dichloro diphenyl diselenide and 2',2,4',4,6',6-hexamethyl diphenyl diselenide, in the range of 10-100muM, induced a significant increase in Damage Index (DI). The genotoxic effect of all compounds was associated with high frequencies of cells with damage level 4 and all compounds caused a decrease in cell viability. Our results suggest that the selenium compounds tested were genotoxic and cytotoxic to human leukocytes cells in vitro and that the organoselenium amino acid derivatives ((S)-tert-butyl 1-diselenide-3-methylbutan-2-ylcarbamate, (S)-tert-butyl 1-diselenide-3-phenylpropan-2-ylcarbamate, (S)-2-amino-1-diselenide-3-methylpropanyl and (S)-2-amino-1-diselenide-3-phenylpropanyl) were more genotoxic than aromatic derivatives (3',3-ditrifluoromethyl diphenyl diselenide, 4',4-dimethoxy diphenyl diselenide, 4',4-dichloro diphenyl diselenide and 2',2,4',4,6',6-hexamethyl diphenyl diselenide). These effects may be linked to the pro-oxidant activity exhibited by selenium compounds when used in relatively high concentrations.

Studies on the antioxidant effect and interaction of diphenyl diselenide and dicholesteroyl diselenide with hepatic delta-aminolevulinic acid dehydratase and isoforms of lactate dehydrogenase.

Studies on the interaction of dicholesteroyl diselenide (DCDS) and diphenyl diselenide (DPDS) with hepatic delta-aminolevulinic acid dehydratase (ALA-D) and different isoforms of lactate dehydrogenase (LDH) from different tissues were investigated. In addition, their antioxidant effects were tested in vitro by measuring the ability of the compounds to inhibit the formation of hepatic thiobarbituric acid reactive species (TBARS) induced by both iron (II) and sodium nitroprusside (SNP). The results show that while DPDS markedly inhibited the formation of TBARS induced by both iron (II) and SNP, DCDS did not. Also, the activities of hepatic delta-aminolevulinic acid dehydratase (ALA-D) and different isoforms of lactate dehydrogenase (LDH) were significantly inhibited by both DPDS and DCDS. Moreover, we further observed that the in vitro inhibition of different isoforms of lactate dehydrogenase by DCDS and DPDS likely involves the modification of the groups at the NAD+ binding site of the enzyme. Since organoselenides interacts with thiol groups on proteins, we conclude that the inhibition of different isoforms of lactate dehydrogenase by DPDS and DCDS possibly involves the modification of the thiol groups at the NAD+ binding site of the enzyme.

Diphenyl diselenide reverses gastric lesions in rats: Involvement of oxidative stress.

The aim of the present study was to evaluate if diphenyl diselenide administered by oral route was effective in restoring gastric lesions induced by ethanol. The possible involvement of oxidative stress in diphenyl diselenide antiulcer effect was also evaluated. Different doses of diphenyl diselenide (dissolved in soya bean oil, 1mL/kg) were administered orally 1h before (pre-treatment study) or 1h after ethanol (70%, v/v, 2mL/kg, post-treatment study). Ulcer lesions were quantified 1h after ethanol administration (pre-treatment protocol) or 1h after diphenyl diselenide study (post-treatment protocol). Diphenyl diselenide (0.1-10mg/kg or 0.32-32micromol/kg), when administered previously or posteriorly prevented and reversed respectively, the development of gastric lesions induced by ethanol in rats. A number of markers of oxidative stress were examined in rat stomach including thiobarbituric acid reactive species (TBARS), catalase (CAT), superoxide dismutase (SOD), non-protein thiol groups (NPSH) and ascorbic acid. In addition to attenuating the gastric lesions, low doses of diphenyl diselenide prevented (pre-treatment) or reversed (post-treatment) the ethanol-induced changes in TBARS, SOD activity and ascorbic acid content. In conclusion, the present data reveal that diphenyl diselenide, administered by oral route, possesses an antiulcer effect by modulating antioxidant mechanisms.

Dietary diphenyl diselenide reduces the STZ-induced toxicity.

Oxidative stress is implicated in the pathogenesis of diabetes mellitus. Selenium supplementation has some benefits in experimental models of diabetes mellitus. This study evaluated whether dietary diphenyl diselenide, a simple synthetic organoselenium compound with antioxidant properties, reduces the streptozotocin (STZ)-induced toxicity. STZ-induced diabetic rats were fed with either standard and diphenyl diselenide (10 ppm) supplemented diets. In experimental trials, dietary diphenyl diselenide significantly decreased mortality rate (p<0.05) induced by STZ treatment. No correlation between this effect and glycemic levels were found. Diphenyl diselenide intake also promoted an increase in vitamin C, -SH levels (liver, kidney and blood) and in catalase (liver and kidney) activity, which were decreased in STZ-treated rats. In enzyme assays, diphenyl diselenide supplementation caused a significant improvement in platelets NTPDase and 5'-nucleotidase activities in STZ-induced diabetic rats when compared to the control and diabetic groups (p<0.05). Nevertheless, this supplementation did not modify the inhibition induced by STZ in delta-ALA-D activity. Our findings suggest that diphenyl diselenide compound showed beneficial effects against the development of diabetes by exhibiting antioxidant properties.

Potentially adverse interactions between haloperidol and valerian.

This study was designed to determine whether the treatment with haloperidol (HP), valerian or both in association impairs the liver or kidney functions. Valerian alone did not affect oxidative stress parameters in the liver or kidney of rats. HP alone only increased glutathione (GSH) depletion in liver, but not in kidney. However, when HP was associated with valerian, an increase in lipid peroxidation levels and dichlorofluorescein (DCFH) reactive species production was observed in the hepatic tissue. Superoxide dismutase (SOD) and Catalase (CAT) activities were not affected by the HP plus valerian treatment in the liver and kidney of rats. HP and valerian when administered independently did not affect the activity of hepatic and renal delta-aminolevulinate dehydratase (delta-ALA-D), however, these drugs administered concomitantly provoked an inhibition of hepatic delta-ALA-D activity. The delta-ALA-D reactivation index was higher in rats treated with HP plus valerian than other treated groups. These results strengthen the view that delta-ALA-D can be considered a marker for oxidative stress. Serum aspartate aminotransferase (AST) activity was not altered by any treatment. However, serum alanine aminotransferase (ALT) activity was higher in the HP group and HP plus valerian group. Our findings suggest adverse interactions between haloperidol and valerian.

Antioxidant and hepatoprotective activity of aqueous extract of Solanum fastigiatum (false "Jurubeba") against paracetamol-induced liver damage in mice.

AIM OF THE STUDY: Solanum fastigiatum is a medicinal plant widely distributed in the south of Brazil and has been used mainly to treat hepatitis, spleen disorders, uterine tumors, irritable bowel syndrome and chronic gastritis. The present research was aimed to evaluate the potential antioxidant and hepatoprotective activity of aqueous extracts of leaves using in vitro and in vivo models to validate the folkloric use of the plant. MATERIALS AND METHODS: Antioxidant activity was evaluated by different assays, including thiobarbituric acid reactive species (TBARS), total antioxidant, 2,2-diphenlyl-1-picrylhydrazyl (DPPH) radical and metal ion-chelating activities. The hepatoprotective activity of the aqueous extracts was studied on mice liver damage induced by paracetamol (250mg/kg) by monitoring biochemical parameters. RESULTS: The extract showed inhibition against TBARS, induced by 10microM FeSO(4) and 5microM sodium nitroprusside in rat liver, brain and phospholipid homogenates from egg yolk. The plant exhibited strong antioxidant activity in the DPPH (IC(50), 68.96+/-1.25microg/ml) assay. The aqueous extract also showed significant hepatoprotective activity that was evident by enzymatic examination and brought back the altered levels of TBARS, non-protein thiol and ascorbic acid to near the normal levels in a dose dependent manner. Acute toxicity studies revealed that the LD(50) value of the extract is more than the dose 4g/kg body weight of mice. CONCLUSIONS: The results indicate that this plant possesses potential antioxidant and hepatoprotective properties and has therapeutic potential for the treatment of liver diseases.

Ilex paraguariensis has antioxidant potential and attenuates haloperidol-induced orofacial dyskinesia and memory dysfunction in rats.

Tardive dyskinesia (TD) is a syndrome associated with administration of antipsychotics drugs and may be a consequence of a free radical increase. Ilex paraguariensis (IP), rich in polyphenols, is used to prepare a tea-like beverage, the "mate", and has been investigated for its antioxidant action. Here, we examined the aqueous extract of IP on in vitro TBARS production and in vivo study, using two behavioral models, i.e., haloperidol-induced orofacial dyskinesia (evaluated measuring vacuous chewing movements, VCMs) and memory dysfunction, evaluated in a water-maze task. In vitro, we examine different concentrations of IP against the basal, Fe(II) and sodium nitruproside-induced TBARS production in rat brain homogenate. IP extract was able to prevent the basal formation of TBARS (IC50 = 6.6 mg/ml) and TBARS induced by SNP (IC50 = 3.7 mg/ml) and Fe(II) (IC50= 4.8 mg/ml). Haloperidol administration (12 mg/kg/week, im, x4 weeks) increased VCMs (p <0.001). Rats treated with mate (50 g/l, ad libitum, 60 days) did not exhibit the increase in VCMs observed in control rats treated with haloperidol (p <0.001). In the water maze task, haloperidol treated animals displayed an impairment in memory acquisition (p <0.05) compared to rats treated with vehicle. The "mate" prevented the effects of haloperidol in this behavioral paradigm. Our results indicate that IP exhibits an antioxidant role probably related to the presence of polyphenols. The benefit of IP is possibly related to an indirect modulation of oxidative stress.

Ebselen and diorganylchalcogenides decrease in vitro glutamate uptake by rat brain slices: prevention by DTT and GSH.

The purpose of this study was to investigate the possible involvement of the glutamatergic system in the neurotoxicity of diorganylchalcogenides or organochalcogenides from slices of cerebral cortex in different ages of development: 12- and 60-day-old rats. Glutamate uptake was evaluated in cortical slices of 12 and 60 days old rats. Cortex slices were incubated with three different organochalcogenides with or without reduced glutathione or dithiothreitol. At 100 microM, ebselen, diphenyl diselenide (PhSe)2 and diphenyl ditelluride (PhTe)2 in vitro inhibited the [3H]glutamate uptake in both age. Both 60-day-old rats and for 12-day-old rats, GSH and DTT prevented the (PhTe)2-induced inhibition of glutamate uptake but did not protect the inhibition caused by ebselen and (PhSe)2. These findings suggest that the neurotoxicity of organochalcogenides could be related to their effects on brain glutamate uptake, conceivably involving a redox modulation of reactive amino acids from the glutamate transporter proteins.