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Joao Rocha - One of the best experts on this subject based on the ideXlab platform.

  • Diphenyl Diselenide Modulates Gene Expression of Antioxidant Enzymes in the Cerebral Cortex, Hippocampus and Striatum of Female Hypothyroid Rats
    Neuroendocrinology, 2014
    Co-Authors: Glaecir Roseni Mundstock Dias, Joao Rocha, Cristina W Nogueira, Rafael De Lima Portella, Félix Alexandre Antunes Soares, Ronaldo Medeiros Golombieski, Guilherme Pires Amaral, Nilda Vargas Barbosa
    Abstract:

    Introduction: Cellular antioxidant signaling can be altered either by thyroid disturbances or by selenium status. Aims: To investigate whether or not dietary Diphenyl Diselenide can modify the expression of genes of antioxidant enzymes and endpoint markers of oxidative stress under hypothyroid conditions. Methods: Female rats were rendered hypothyroid by continuous exposure to methimazole (MTZ; 20 mg/100 ml in the drinking water) for 3 months. Concomitantly, MTZ-treated rats were either fed or not with a diet containing Diphenyl Diselenide (5 ppm). mRNA levels of antioxidant enzymes and antioxidant/oxidant status were determined in the cerebral cortex, hippocampus and striatum. Results: Hypothyroidism caused a marked upregulation in mRNA expression of catalase, superoxide dismutase (SOD-1, SOD-3), glutathione peroxidase (GPx-1, GPx-4) and thioredoxin reductase (TrxR-1) in brain structures. SOD-2 was increased in the cortex and striatum, while TrxR-2 increased in the cerebral cortex. The increase in mRNA expression of antioxidant enzymes was positively correlated with the Nrf-2 transcription in the cortex and hippocampus. Hypothyroidism caused oxidative stress, namely an increase in lipid peroxidation and reactive oxygen species levels in the hippocampus and striatum, and a decrease in nonprotein thiols in the cerebral cortex. Diphenyl Diselenide was effective in reducing brain oxidative stress and normalizing most of the changes observed in gene expression of antioxidant enzymes. Conclusion: The present work corroborates and extends that hypothyroidism disrupts antioxidant enzyme gene expression and causes oxidative stress in the brain. Furthermore, Diphenyl Diselenide may be considered a promising molecule to counteract these effects in a hypothyroidism state.

  • Interaction Profile of Diphenyl Diselenide with Pharmacologically Significant Thiols
    Molecules (Basel Switzerland), 2012
    Co-Authors: Waseem Hassan, Joao Rocha
    Abstract:

    Diphenyl Diselenide has shown interesting biological activities in various free-radical-induced damage models and can be considered as a potential candidate drug against oxidative stress. Apart from its anti-oxidant activity, this compound can oxidize various thiols. However there are no detailed studies in the literature about the thiol oxidase-like activity of this compound against biologically significant mono and di-thiols with respect to various pH conditions. Keeping in mind the scarcity of data in this area of organochalcogen chemistry, we report for the first time the kinetics of thiol oxidation by Diphenyl Diselenide, which was carried out in a commonly used phosphate buffer, not only at physiological pH, but also at a number of acidic values. The relative reactivities of the different thiols with Diphenyl Diselenide were independent of the pKa of the thiol group, such that at pH 7.4, cysteine and dithiothreitol were the most reactive, while 2,3-dimercapto-1-propanesulfonic acid and glutathione were weakly reactive and extremely low reactivity was observed with dimercaptosuccinic acid. Rate of oxidation was dependent on the pH of the incubation medium. The results obtained will help us in the design of rational strategies for the safe pharmacological use of Diphenyl Diselenide.

  • Diphenyl Diselenide and analogs are substrates of cerebral rat thioredoxin reductase: A pathway for their neuroprotective effects
    Neuroscience letters, 2011
    Co-Authors: Andressa Sausen De Freitas, Joao Rocha
    Abstract:

    Thioredoxin reductase (TrxR) isoforms play important roles in cell physiology, protecting cells against oxidative processes. In addition to its endogenous substrates (Trx isoforms), hepatic TrxR can reduce organic selenium compounds such as ebselen and Diphenyl Diselenide to their selenol intermediates, which can be involved in their hepatoprotective properties. Taking this into account, the aim of the present study was to evaluate the hypothesis that ebselen, Diphenyl Diselenide and its analogs (4,4'-bistrifluoromethylDiphenyl Diselenide, 4,4'-bismethoxyDiphenyl Diselenide, 4.4'-biscarboxy-Diphenyl Diselenide, 4,4'-bischloroDiphenyl Diselenide, 2,4,6,2',4',6'-hexamethylDiphenyl Diselenide) could be substrates of rat brain TrxR. In the presence of partially purified rat brain TrxR, Diphenyl Diselenide, bismethoxyDiphenyl Diselenide and bischloroDiphenyl Diselenide (at 10, 15 and 20μM) stimulated NADPH oxidation, indicating that they are substrates of brain TrxR. In contrast, ebselen and bistrifluoromethylDiphenyl Diselenide, that have been previously demonstrated to be substrate of hepatic TrxR, were not reduced by rat brain TrxR. The results presented here suggest that Diphenyl Diselenide can exert neuroprotective effects by mimicking glutathione peroxidase activity and also via its reduction by TrxR. However, ebselen was not reduced by brain TrxR, indicating that the neuroprotective properties of this compound is possibly mediate by its glutathione peroxidase-like activity.

  • Reduction of Diphenyl Diselenide and analogs by mammalian thioredoxin reductase is independent of their gluthathione peroxidase-like activity: a possible novel pathway for their antioxidant activity.
    Molecules (Basel Switzerland), 2010
    Co-Authors: Andressa Sausen De Freitas, Caroline Wagner, Diego Alves, Jéssie Haigert Sudati, Alessandro De Souza Prestes, Lisiane O. Porciúncula, Ige Joseph Kade, Joao Rocha
    Abstract:

    Since the successful use of the organoselenium drug ebselen in clinical trials for the treatment of neuropathological conditions associated with oxidative stress, there have been concerted efforts geared towards understanding the precise mechanism of action of ebselen and other organoselenium compounds, especially the diorganyl Diselenides such as Diphenyl Diselenide, and its analogs. Although the mechanism of action of ebselen and other organoselenium compounds has been shown to be related to their ability to generally mimic native glutathione peroxidase (GPx), only ebselen however has been shown to serve as a substrate for the mammalian thioredoxin reductase (TrxR), demonstrating another component of its pharmacological mechanisms. In fact, there is a dearth of information on the ability of other organoselenium compounds, especially Diphenyl Diselenide and its analogs, to serve as substrates for the mammalian enzyme thioredoxin reductase. Interestingly, Diphenyl Diselenide shares several antioxidant and neuroprotective properties with ebselen. Hence in the present study, we tested the hypothesis that Diphenyl Diselenide and some of its analogs (4,4’-bistrifluoromethylDiphenyl Diselenide, 4,4’-bismethoxy-Diphenyl Diselenide, 4.4’-biscarboxyDiphenyl Diselenide, 4,4’-bischloroDiphenyl Diselenide, 2,4,6,2’,4’,6’-hexamethylDiphenyl Diselenide) could also be substrates for rat hepatic TrxR. Here we show for the first time that Diselenides are good substrates for mammalian TrxR, but not necessarily good mimetics of GPx, and vice versa. For instance, bis-methoxyDiphenyl Diselenide had no GPx activity, whereas it was a good substrate for reduction by TrxR. Our experimental observations indicate a possible dissociation between the two pathways for peroxide degradation (either via substrate for TrxR or as a mimic of GPx). Consequently, the antioxidant activity of Diphenyl Diselenide and analogs can be attributed to their capacity to be substrates for mammalian TrxR and we therefore conclude that subtle changes in the aryl moiety of Diselenides can be used as tool for dissociation of GPx or TrxR pathways as mechanism triggering their antioxidant activities.

  • Diphenyl Diselenide behaves differently than ebselen under different pH media in rat's liver preparations.
    Pathology research and practice, 2010
    Co-Authors: Waseem Hassan, Mohammad Ibrahim, Joao Rocha
    Abstract:

    Abstract The anti-oxidant potential of Diphenyl Diselenide and ebselen against low pH-mediated peroxidation processes in rat's liver preparation are unknown. For this purpose, we have determined anti-oxidant activities of both compounds at a range of various pH (7.4–5.4) values. Low pH increased the rate of lipid peroxidation in the absence of Fe +2 (20 μmol) in liver homogenates. This higher extent of lipid peroxidation can be explained by the mobilized iron, which may come from reserves where it is weakly bound. The addition of iron (Fe) chelator desferoxamine (DFO, 1 mmol) to reaction medium completely inhibited the peroxidation processes at all studied pH values. Diphenyl Diselenide (0–100 μmol) significantly protected lipid peroxidation at all studied pH values, while ebselen (0–100 μmol) did not offer any protection. The differences in activities of Diphenyl Diselenide and ebselen have been explained with reference to the active selenol formation using their catalytic reactions. The anti-oxidant potential of Diphenyl Diselenide is confirmed against acidosis-catalyzed oxidative stress in rat liver homogenates.

Cristina W Nogueira - One of the best experts on this subject based on the ideXlab platform.

  • Diphenyl Diselenide and its interaction with antifungals against Aspergillus spp.
    Medical mycology, 2020
    Co-Authors: Aryse Martins Melo, Cristina W Nogueira, Gilson Zeni, Vanice Rodrigues Poester, Mariana Rodrigues Trapaga, Marife Martinez, Gabriele Sass, David A. Stevens, Melissa Orzechowski Xavier
    Abstract:

    Given the few antifungal classes available to treat aspergillosis, this study aimed to evaluate the in vitro antifungal activity of Diphenyl Diselenide (PhSe)2 alone and in combination with classical antifungals against Aspergillus spp., and its in vivo activity in a systemic experimental aspergillosis model. We performed in vitro broth microdilution assay of (PhSe)2 against 32 Aspergillus isolates; and a checkboard assay to test the interaction of this compound with itraconazole (ITC), voriconazole (VRC), amphotericin B (AMB), and caspofungin (CAS), against nine Aspergillus isolates. An experimental model of invasive aspergillosis in mice was studied, and survival curves were compared between an untreated group and groups treated with 100 mg/kg ITC, or (PhSe)2 in different dosages (10 mg/kg, 50 mg/kg and 100 mg/kg). All Aspergillus non-fumigatus and 50% of A. fumigatus were inhibited by (PhSe)2 in concentrations ≤ 64 µg/ml, with significant differences in MICs between the sections. Synergism or additive effect in the in vitro (PhSe)2 interaction with VRC and CAS was observed against the majority of isolates, and with ITC against the non-fumigatus strains. In addition to the inhibitory interaction, (PhSe)2 was able to add a fungicidal effect to CAS. Survival curves from the systemic experimental aspergillosis model demonstrated that the inoculum caused an acute and lethal infection in mice, and no treatment applied significantly prolonged survival over that of the control group. The results highlight the promising activity of (PhSe)2 against Aspergillus species, but more in vivo studies are needed to determine its potential applicability in aspergillosis treatment. LAY SUMMARY The activity of Diphenyl Diselenide (PhSe)2 alone and in combination with itraconazole, voriconazole, and caspofungin, is described against three of the most pathogenic Aspergillus sections. (PhSe)2 may prove useful in therapy of infection in future; further study is required.

  • Opioid system contribution to the antidepressant-like action of m-trifluoromethyl-Diphenyl Diselenide in mice: A compound devoid of tolerance and withdrawal syndrome.
    Journal of psychopharmacology (Oxford England), 2017
    Co-Authors: Suzan Gonçalves Rosa, Ana Paula Pesarico, Carolina F Tagliapietra, Sônia Ca Da Luz, Cristina W Nogueira
    Abstract:

    Animal and clinical researches indicate that the opioid system exerts a crucial role in the etiology of mood disorders and is a target for intervention in depression treatment. This study investigated the contribution of the opioid system to the antidepressant-like action of acute or repeated m-trifluoromethyl-Diphenyl Diselenide administration to Swiss mice. m-Trifluoromethyl-Diphenyl Diselenide (50 mg/kg, intragastric) produced an antidepressant-like action in the forced swimming test from 30 min to 24 h after treatment. This effect was blocked by the µ and δ-opioid receptor antagonists, naloxonazine (10 mg/kg, intraperitoneally) and naltrindole (3 mg/kg, intraperitoneally), and it was potentiated by a κ-opioid receptor antagonist, norbinaltrophimine (1 mg/kg, subcutaneously ). Combined treatment with subeffective doses of m-trifluoromethyl-Diphenyl Diselenide (10 mg/kg, intragastric) and morphine (1 mg/kg, subcutaneously) resulted in a synergistic antidepressant-like effect. The opioid system contribution to the m-trifluoromethyl-Diphenyl Diselenide antidepressant-like action was also demonstrated in the modified tail suspension test, decreasing mouse immobility and swinging time and increasing curling time, results similar to those observed using morphine, a positive control. Treatment with m-trifluoromethyl-Diphenyl Diselenide induced neither tolerance to the antidepressant-like action nor physical signs of withdrawal, which could be associated with the fact that m-trifluoromethyl-Diphenyl Diselenide did not change the mouse cortical and hippocampal glutamate uptake and release. m-Trifluoromethyl-Diphenyl Diselenide treatments altered neither locomotor nor toxicological parameters in mice. These findings demonstrate that m-trifluoromethyl-Diphenyl Diselenide elicited an antidepressant-like action by direct or indirect μ and δ-opioid receptor activation and the κ-opioid receptor blockade, without inducing tolerance, physical signs of withdrawal and toxicity.

  • Diphenyl Diselenide Modulates Gene Expression of Antioxidant Enzymes in the Cerebral Cortex, Hippocampus and Striatum of Female Hypothyroid Rats
    Neuroendocrinology, 2014
    Co-Authors: Glaecir Roseni Mundstock Dias, Joao Rocha, Cristina W Nogueira, Rafael De Lima Portella, Félix Alexandre Antunes Soares, Ronaldo Medeiros Golombieski, Guilherme Pires Amaral, Nilda Vargas Barbosa
    Abstract:

    Introduction: Cellular antioxidant signaling can be altered either by thyroid disturbances or by selenium status. Aims: To investigate whether or not dietary Diphenyl Diselenide can modify the expression of genes of antioxidant enzymes and endpoint markers of oxidative stress under hypothyroid conditions. Methods: Female rats were rendered hypothyroid by continuous exposure to methimazole (MTZ; 20 mg/100 ml in the drinking water) for 3 months. Concomitantly, MTZ-treated rats were either fed or not with a diet containing Diphenyl Diselenide (5 ppm). mRNA levels of antioxidant enzymes and antioxidant/oxidant status were determined in the cerebral cortex, hippocampus and striatum. Results: Hypothyroidism caused a marked upregulation in mRNA expression of catalase, superoxide dismutase (SOD-1, SOD-3), glutathione peroxidase (GPx-1, GPx-4) and thioredoxin reductase (TrxR-1) in brain structures. SOD-2 was increased in the cortex and striatum, while TrxR-2 increased in the cerebral cortex. The increase in mRNA expression of antioxidant enzymes was positively correlated with the Nrf-2 transcription in the cortex and hippocampus. Hypothyroidism caused oxidative stress, namely an increase in lipid peroxidation and reactive oxygen species levels in the hippocampus and striatum, and a decrease in nonprotein thiols in the cerebral cortex. Diphenyl Diselenide was effective in reducing brain oxidative stress and normalizing most of the changes observed in gene expression of antioxidant enzymes. Conclusion: The present work corroborates and extends that hypothyroidism disrupts antioxidant enzyme gene expression and causes oxidative stress in the brain. Furthermore, Diphenyl Diselenide may be considered a promising molecule to counteract these effects in a hypothyroidism state.

  • Diphenyl Diselenide supplemented diet reduces depressive-like behavior in hypothyroid female rats
    Physiology & behavior, 2013
    Co-Authors: Glaecir Roseni Mundstock Dias, Cristina W Nogueira, Tielle Moraes De Almeida, Jéssie Haigert Sudati, Fernando Dobrachinski, Sandra Sartoretto Pavin, Félix Alexandre Antunes Soares, Nilda Vargas Barbosa
    Abstract:

    Abstract Hypothyroidism has been associated to psychiatric disorder development and tissue oxidative damage. In this study, we evaluated the effect of Diphenyl Diselenide supplementation on depressive-like behavior triggered by methimazole exposure in female rats. Additionally, thiobarbituric acid reactive substances (TBARS), reactive oxygen species (ROS) and non-protein thiol (NP-SH) levels were analyzed in cerebral cortex, hippocampus and striatum structures of rats. Monoamine oxidase (MAO) activity was evaluated in total brain. Firstly, female rats received methimazole (MTZ) 20 mg/100 ml in the drinking water for 30 days and were evaluated in open-field and forced swimming tests (FST). In this set of experiments, the rats exposed to MTZ presented a depressive-like behavior, which was evidenced by a significant increase in the immobility time when compared to control group. Thereafter, MTZ-induced hypothyroid rats received either a standard or a diet containing 5 ppm of Diphenyl Diselenide, and then they were evaluated monthly in open-field and FST tests during 3 months. No alteration on the locomotor performance was observed among the groups. The depressive-like behavior of hypothyroid rats was blunted by Diphenyl Diselenide supplementation during all experimental periods. The levels of thyroid hormones remained low in MTZ exposed groups until the end of experimental period. The MTZ group had an increase in TBARS and ROS levels that were restored by Diphenyl Diselenide supplementation. NP-SH content of cerebral structures was not modified by MTZ exposure and/or Diphenyl Diselenide supplementation. Diphenyl Diselenide supplementation restored the MAO B activity that was decreased in MTZ group. In summary, our results show that hypothyroidism induced by MTZ methimazole triggers a depressive-like behavior in female rats and that dietary Diphenyl Diselenide was able to reduce this effect.

  • Diphenyl Diselenide-Loaded Nanocapsules: Preparation and Biological Distribution
    Applied biochemistry and biotechnology, 2013
    Co-Authors: Camila Ferrazza Alves Giordani, Cristina W Nogueira, Marina Prigol, Diego De Souza, Luciano Dornelles, Marta P. Alves, Oscar E. D. Rodrigues
    Abstract:

    Over the past years, organoselenium compounds have been aimed as targets of interest in organic synthesis. Diphenyl Diselenide [(PhSe)2] is an important example of this class showing several pharmacological properties. However, the poor water-solubility and its low oral bioavailability may be considered an obstruction for the clinical utility of this compound. For this reason, the use of nanocapsules is a prominent approach to increase the bioavailability of lipophylic molecules. This study aims to prepare Diphenyl Diselenide-loaded nanocapsules with two different concentrations, by interfacial deposition of the preformed polymer in order to develop a system to improve its oral bioavailability. The drug-loaded nanocapsules with 1.56 and 5 mg ml−1 and unloaded nanocapsule suspensions presented macroscopic homogeneous aspect, as well as submicronic sizes, low polydispersity, negative zeta potentials and slightly acid or neutral pH values. The biological tests of selenium distribution in different tissues of mice show a higher bioavailability of the (PhSe)2 nanocapsules when compared with the free (PhSe)2, both administered by per oral route at the dose of 50 mg/kg, showing a prominent influence of the nanocarries systems for biological properties of this organochalcogenium compound.

Gilson Zeni - One of the best experts on this subject based on the ideXlab platform.

  • Diphenyl Diselenide and its interaction with antifungals against Aspergillus spp.
    Medical mycology, 2020
    Co-Authors: Aryse Martins Melo, Cristina W Nogueira, Gilson Zeni, Vanice Rodrigues Poester, Mariana Rodrigues Trapaga, Marife Martinez, Gabriele Sass, David A. Stevens, Melissa Orzechowski Xavier
    Abstract:

    Given the few antifungal classes available to treat aspergillosis, this study aimed to evaluate the in vitro antifungal activity of Diphenyl Diselenide (PhSe)2 alone and in combination with classical antifungals against Aspergillus spp., and its in vivo activity in a systemic experimental aspergillosis model. We performed in vitro broth microdilution assay of (PhSe)2 against 32 Aspergillus isolates; and a checkboard assay to test the interaction of this compound with itraconazole (ITC), voriconazole (VRC), amphotericin B (AMB), and caspofungin (CAS), against nine Aspergillus isolates. An experimental model of invasive aspergillosis in mice was studied, and survival curves were compared between an untreated group and groups treated with 100 mg/kg ITC, or (PhSe)2 in different dosages (10 mg/kg, 50 mg/kg and 100 mg/kg). All Aspergillus non-fumigatus and 50% of A. fumigatus were inhibited by (PhSe)2 in concentrations ≤ 64 µg/ml, with significant differences in MICs between the sections. Synergism or additive effect in the in vitro (PhSe)2 interaction with VRC and CAS was observed against the majority of isolates, and with ITC against the non-fumigatus strains. In addition to the inhibitory interaction, (PhSe)2 was able to add a fungicidal effect to CAS. Survival curves from the systemic experimental aspergillosis model demonstrated that the inoculum caused an acute and lethal infection in mice, and no treatment applied significantly prolonged survival over that of the control group. The results highlight the promising activity of (PhSe)2 against Aspergillus species, but more in vivo studies are needed to determine its potential applicability in aspergillosis treatment. LAY SUMMARY The activity of Diphenyl Diselenide (PhSe)2 alone and in combination with itraconazole, voriconazole, and caspofungin, is described against three of the most pathogenic Aspergillus sections. (PhSe)2 may prove useful in therapy of infection in future; further study is required.

  • Antifungal activities of Diphenyl Diselenide and ebselen alone and in combination with antifungal agents against Fusarium spp.
    Medical mycology, 2016
    Co-Authors: Tarcieli Pozzebon Venturini, Gilson Zeni, Érico S. Loreto, Janio Morais Santurio, Francieli Chassot, Jéssica Tairine Keller, M.i. Azevedo, Sydney Hartz Alves
    Abstract:

    Herein, we describe the in vitro activity of a combination of the organoselenium compounds Diphenyl Diselenide and ebselen alone and in combination with amphotericin B, caspofungin, itraconazole, and voriconazole against 25 clinical isolates of Fusarium spp. For this analysis, we used the broth microdilution method based on the M38-A2 technique and checkerboard microdilution method. Diphenyl Diselenide (MIC range = 4-32 μg/ml) and ebselen (MIC range = 2-8 μg/ml) showed in vitro activity against the isolates tested. The most effective combinations were (synergism rates): ebselen + amphotericin B (88%), ebselen + voriconazole (80%), Diphenyl Diselenide + amphotericin B (72%), and Diphenyl Diselenide + voriconazole (64%). Combination with caspofungin resulted in low rates of synergism: ebselen + caspofungin, 36%, and Diphenyl Diselenide + caspofungin, 28%; combination with itraconazole demonstrated indifferent interactions. Antagonistic effects were not observed for any of the combinations tested. Our findings suggest that the antifungal potential of Diphenyl Diselenide and ebselen deserves further investigation in in vivo experimental models, especially in combination with amphotericin B and voriconazole.

  • Physicochemical and Biochemical Profiling of Diphenyl Diselenide
    Applied biochemistry and biotechnology, 2013
    Co-Authors: Marina Prigol, Cristina W Nogueira, Gilson Zeni, Maria Rosário Bronze, Luis Constantino
    Abstract:

    The objective of the present study was to evaluate the physicochemical and biochemical profiling of Diphenyl Diselenide (PhSe)2, a selenoorganic compound with biological activity. Experimental protocols were established for chemical stability in isotonic phosphate buffer (PBS) pH 7.4 and in simulated gastric and intestinal fluids, biological stability (bovine serum albumin (BSA) and plasma), solubility in PBS pH 7.4, distribution coefficient (Log D) in octanol/PBS, and determination of free (PhSe)2 concentrations in BSA and plasma by using liquid chromatography with ultraviolet detection and tandem mass spectrometry. (PhSe)2 was found to be chemically stable and not susceptible to degradation in plasma. The aqueous solubility was 0.98 ± 0.072 μM and the Log D in octanol/PBS system was found to be 3.13. The percentage of unbound fractions of (PhSe)2 obtained by equilibrium dialysis from BSA and plasma incubated with 100 μM (PhSe)2 were 0.69 ± 0.12 and 0.44 ± 0.09 %, respectively. The findings indicated that (PhSe)2 presents chemical and biological stability. Though, the compound showed low aqueous solubility, high Log D value and high binding to plasmatic protein. These data contribute to the knowledge of the toxicokinetic properties of (PhSe)2 and further explain its low bioavailability in experimental models.

  • Diphenyl Diselenide in vitro and in vivo activity against the oomycete Pythium insidiosum.
    Veterinary microbiology, 2011
    Co-Authors: Erico Silva Loreto, Sydney Hartz Alves, Janio Morais Santurio, Cristina Wayne Nogueira, Gilson Zeni
    Abstract:

    This study evaluated the in vitro activity of Diphenyl Diselenide against 19 Pythium insidiosum isolates and the in vivo therapeutic response of rabbits with experimentally induced pythiosis. In vitro: susceptibility tests were performed using the broth macrodilution method in accordance with the CLSI document M38-A2. The criteria for interpretation were as follows: MIC-1 and MIC-2 (inhibition of 90% and 100% of mycelium growth, respectively) and the minimum fungicide concentration (MIC-3). In vivo: twenty rabbits were divided into four groups with five animals each and treated for 40 consecutive days: groups 1 and 2 (experimentally induced pythiosis) were treated with Diphenyl Diselenide (10mg/kg/day) and canola oil (1 mL/kg/day), respectively; groups 3 and 4 (controls) were treated with canola oil (1 mL/kg/day) and Diphenyl Diselenide (10mg/kg/day), respectively. Toxicity was evaluated using biochemical and haematological parameters. In vitro susceptibility tests showed that 89.4% of isolates had a MIC-1 ≤ 0.5 μg/mL, 84.2% of isolates had a MIC-2 ≤ 1.0 μg/mL and 94.7% of isolates had a MIC-3 ≤ 2.0 μg/mL. The in vivo assay suggested that this compound has a fungistatic activity, and the biochemical and haematological parameters indicated that there was no renal, hepatic or haematological toxicity. The comparison of the unsaturated iron binding capacity levels between animals with and without pythiosis suggested the involvement of iron metabolism in the pathogenesis of pythiosis. This study demonstrated the absence of detectable toxicity caused by Diphenyl Diselenide and the in vitro fungicidal and in vivo fungistatic activities of this drug, which makes it an option for future therapeutic approaches in the treatment of pythiosis.

  • m-Trifluoromethyl-Diphenyl Diselenide attenuates pentylenetetrazole-induced seizures in mice by inhibiting GABA uptake in cerebral cortex slices
    Pharmacological reports : PR, 2009
    Co-Authors: Marina Prigol, Cristina W Nogueira, César Augusto Brüning, Benhur Godoi, Gilson Zeni
    Abstract:

    Abstract The present study investigated the anticonvulsive effect of the disubstituted diaryl Diselenides Diphenyl Diselenide (PhSe) 2 , m -trifluoromethyl-Diphenyl Diselenide ( m -CF 3 -C 6 H 4 Se) 2 , p -chloro-Diphenyl Diselenide ( p -Cl-C 6 H 4 Se) 2 and p -methoxyl-Diphenyl Diselenide ( p -CH 3 O-C 6 H 4 Se) 2 on a chemical model of seizure induced by pentylenetetrazol (PTZ) in mice. (PhSe) 2 , ( p -Cl--C 6 H 4 Se) 2 and ( p -CH 3 O-C 6 H 4 Se) 2 did not abolish seizures induced by PTZ in mice. ( m -CF 3 -C 6 H 4 Se) 2 at the dose of 100 mg/kg significantly prolonged the latency of the onset of the first convulsive episode and reduced the number of animals that presented seizures. To investigate the possible mechanisms involved in the anticonvulsant effect of ( m -CF 3 -C 6 H 4 Se) 2 , mice were submitted to different associations (all drugs in a sub-effective dose); aminooxyacetic acid hemihydrochloride (AOAA, a -aminobutyric acid (GABA)-T inhibitor), diazepam (a GABA A receptor agonist) or DL-2, 4-diamino- n -butyric acid hydrochloride (DABA, an inhibitor of GABA uptake) were pre-administered together with ( m -CF 3 -C 6 H 4 Se) 2 .( m -CF 3 -C 6 H 4 Se) 2 + DABA abolished seizures induced by PTZ in mice. ( m -CF 3 -C 6 H 4 Se) 2 administered alone or with PTZ decreased the levels of GABA uptake in cerebral cortex slices. The present study demonstrates that ( m -CF 3 -C 6 H 4 Se) 2 exerts anticonvulsant action by decreasing the levels of GABA uptake.

Akiya Ogawa - One of the best experts on this subject based on the ideXlab platform.

Brindaban C. Ranu - One of the best experts on this subject based on the ideXlab platform.