The Experts below are selected from a list of 219 Experts worldwide ranked by ideXlab platform

Karam Elbayoumy - One of the best experts on this subject based on the ideXlab platform.

  • the Organoselenium Compound 1 4 phenylenebis methylene selenocyanate inhibits 4 methylnitrosamino 1 3 pyridyl 1 butanone induced tumorgenesis and enhances glutathione related antioxidant levels in a j mouse lung
    Chemico-Biological Interactions, 2006
    Co-Authors: John P Richie, Dhimant Desai, Shantu Amin, Wayne Kleinman, John T Pinto, Karam Elbayoumy
    Abstract:

    Abstract Selenium, in the form of 1,4-phenylenebis(methylene)selenocyanate ( p -XSC) but not Se-enriched yeast (Se-yeast), was highly effective at inhibiting lung tumors induced by the tobacco specific nitrosamine (TSNA) 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in A/J mice and at reducing NNK-induced DNA methylation and 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels in the lung. Our goal was to determine if p -XSC but not Se-yeast is effective at inducing levels of glutathione (GSH)-related antioxidants and reducing markers of GSH oxidation in the NNK-induced lung tumor model. In the first bioassay, 6-week-old mice were fed either control or experimental diets (containing 10 ppm as selenium from p -XSC or Se-yeast) and, beginning at 8 weeks of age, received NNK (3 μmol) by gavage once weekly for 8 weeks. After 18 weeks, p -XSC significantly reduced NNK-induced tumor burden by 74% (10.4 ± 6.0 versus 2.7 ± 1.5 tumors/mouse, P P p -XSC ( P p -XSC alone. In the second bioassay, the time course of effects of p -XSC was examined. As early as one week after initiation of p -XSC feeding lung and blood selenium levels were increased nearly six- and two-fold, respectively. Increases of 120% for GSH and 65% for Cys were observed in p -XSC groups compared to controls within one week after initiation of p -XSC feeding ( P p -XSC-treated mice, regardless of NNK status, suggesting a decrease in the levels of oxidative stress. Altogether, these results indicate that p -XSC is a potent inducer of GSH and related thiol antioxidants in the lung leading to decreased levels of oxidative stress and suggest that p -XSC inhibits tumor formation, in part, by protecting against oxidative damage.

  • induction of preneoplastic lung lesions in guinea pigs by cigarette smoke inhalation and their exacerbation by high dietary levels of vitamins c and e
    Carcinogenesis, 2005
    Co-Authors: Emerich S Fiala, Karam Elbayoumy, Chungxiou Wang, Dhimant Desai, Ock Soon Sohn, Eleanore Seibert, Junji Tsurutani, Phillip A Dennis, Rama S Sodum, Joel Reinhardt
    Abstract:

    : The development of effective chemopreventive agents against cigarette smoke-induced lung cancer could be greatly facilitated by the availability of suitable laboratory animal models. Here we report that male Hartley guinea pigs treated with cigarette smoke by inhalation twice a day for 28 days developed preneoplastic lung lesions, including bronchial hyperplasia, dysplasia and squamous metaplasia, analogous to those found in human smokers. The lesions were accompanied by increased expression of proliferating cell nuclear antigen and activation of the serine/threonine kinase Akt in the bronchial epithelium. In contrast, no lung lesions were found in guinea pigs ('sham smoked') that were submitted to identical procedures but without cigarettes. Compared with a diet low in vitamin C (50 p.p.m.) and vitamin E (15 p.p.m.), a diet high in vitamin C (4000 p.p.m.) and vitamin E (40 p.p.m.) significantly increased the incidence of these lesions. The inclusion of 1,4-phenylenebis(methylene)selenocyanate (p-XSC), a synthetic chemopreventive Organoselenium Compound, in the high vitamin C-high vitamin E diet at a level of 15 p.p.m. as selenium appeared to decrease the lesion incidence. Administration of (-)-epigallocatechin gallate, a powerful green tea polyphenolic antioxidant, at 560 p.p.m. in the drinking water had no effect. As in human smokers, levels of ascorbate in blood plasma, lung, liver and the adrenal glands were significantly decreased by cigarette smoke inhalation. These results identify a relevant in vivo laboratory model of cigarette smoke-induced lung cancer, suggest that p-XSC may have activity as a chemopreventive agent against cigarette smoke-induced lung lesions and provide additional evidence that very high dietary levels of certain antioxidants can have co-carcinogenic activity in cigarette smoke-induced lung cancer.

  • cyclooxygenase 2 expression influences the growth of human large and small cell lung carcinoma lines in athymic mice impact of an Organoselenium Compound on growth regulation
    International Journal of Oncology, 2002
    Co-Authors: Karam Elbayoumy, David P Rose, Nick Papanikolaou, Joanna M Leszczynska, Malisetty V Swamy
    Abstract:

    : Increased expression of cyclooxygenase-2 (COX-2) significantly enhances carcinogenesis and inflammatory reactions. Regulation of COX-2 overexpression may be a reasonable target for cancer chemoprevention. We have tested the hypothesis that levels of COX-2 expression determine the growth of human lung cancer cells in nude mice. Two cell lines, NCI-H460 (non-small cell lung cancer) and NCI-H69 (small cell lung cancer) were selected because the former expresses high levels of COX-2 protein and the latter has no detectable levels. We also examined the effects of 1,4-phenylenebis(methylene)selenocyanate (p-XSC), a highly effective chemopreventive Organoselenium Compound and known inhibitor of COX-2 expression, in vivo, on cell growth and COX-2 expression in vitro in the NCI-H460 cancer cell line. Cells were exposed to p-XSC at levels between 10 and 100 microM for six days and showed toxicity at approximately 50 microM. Pre-exposure of NCI-H460 to non-toxic levels of p-XSC suppressed COX-2 protein expression in a dose-dependent manner. At 40 microM, p-XSC suppressed phorbol myristate acetate (PMA)-induced COX-2 expression in NCI-H460 cells by more than 66%. In vivo studies in athymic mice showed a significant difference in tumor volume between cell lines. Pre-treatment of NCI-H460 cells with a non-toxic dose of p-XSC, prior to their injection into nude mice, significantly suppressed tumor growth when compared to untreated cells. Collectively, the outcome of our in vitro and in vivo studies supports the hypothesis that levels of COX-2 expression determine the extent of human lung tumor growth in athymic mice. Therefore, inhibition of COX-2 expression by agents such as p-XSC provides a strong rationale for the development of future clinical prevention trials.

  • chemoprevention of colon cancer by a glutathione conjugate of 1 4 phenylenebis methylene selenocyanate a novel Organoselenium Compound with low toxicity
    Cancer Research, 2001
    Co-Authors: Chungxiou Wang, Karam Elbayoumy, Barbara Simi, Jose G Rodriguez, Indranie Cooma, Bandaru S Reddy
    Abstract:

    We have consistently shown that several synthetic Organoselenium Compounds are superior cancer chemopreventive agents and less toxic than selenite or certain naturally occurring selenoamino acids. 1,4-Phenylene bis (methylene)selenocyanate ( p -XSC) is the lead Organoselenium Compound in that it has been shown to be the most effective and the least toxic agent in several experimental cancer models. It is not known whether p -XSC or one of its metabolites is responsible for its chemopreventive efficacy. As an initial step, we synthesized one of its putative metabolites, i.e. , the glutathione conjugate of p -XSC ( p -XSe-SG), and determined its stability in the pH range from 2 to 8 and in the diet under normal feeding conditions. We also assessed its maximum tolerated dose and examined its chemopreventive efficacy against azoxymethane (AOM)-induced colon carcinogenesis in male F344 rats. p -XSe-SG proved to be very stable over the pH range tested. The maximum tolerated dose of p -XSe-SG determined in a 6-week subchronic toxicity study was found to be >210 ppm (>40 ppm selenium) when the Compound was added to AIN-76A high-fat diet. To assess the efficacy of this agent in the postinitiation period of colon carcinogenesis, male F344 rats 6 weeks of age were fed the high-fat diet, and at beginning of weeks 7 and 8, all of the rats intended for carcinogen treatment were given AOM at a dose of 15 mg/kg body weight by s.c. injection. Two days after the carcinogen treatment, the groups of rats consuming the high-fat control diet began their respective high-fat experimental diet regimens with 0, 56, or 84 ppm p -XSe-SG (0.1, 10, and 15 ppm of selenium) supplementation. All animals continued on their respective diets for 38 weeks after the AOM-treatment and were then killed. Colon tumors were evaluated histologically using routine procedures and were also analyzed for cyclooxygenase (COX)-1 and COX-2 expression and enzymatic activities. The results indicate that p -XSeSG administered during the post-initiation stage significantly inhibited both the incidence ( P P P p -XSe-SG in the diet significantly suppressed total COX activity ( P P p -XSe-SG, is stable in the diet and at wide pH ranges, inhibits colon carcinogenesis when administered during the postinitiation stage, and inhibits COX activity. Compared with previous efficacy studies and considering the toxicity associated with selenium, p -XSe-SG seems to be the least toxic Organoselenium chemopreventive agent thus far tested in the experimental colon carcinogenesis. Studies are in progress to delineate whether p -XSe-SG is also effective when administered during the progression stage of colon carcinogenesis.

  • chemoprevention of lung tumorigenesis induced by a mixture of benzo a pyrene and 4 methylnitrosamino 1 3 pyridyl 1 butanone by the Organoselenium Compound 1 4 phenylenebis methylene selenocyanate
    Cancer Letters, 2000
    Co-Authors: Bogdan Prokopczyk, Jose Rosa, Dhimant Desai, Shantu Amin, Ock Soon Sohn, Emerich S Fiala, Karam Elbayoumy
    Abstract:

    We evaluated the chemopreventive efficacy of the Organoselenium Compound 1,4-phenylenebis(methylene)selenocyanate (p-XSC) against the development of tumors of the lung and forestomach induced by a mixture of benzo(a)pyrene (B(a)P) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), two of the major lung carcinogens present in tobacco smoke. A/J mice (20 mice/group) were given intragastric doses of a mixture of B(a)P (3 μmol/mouse) and NNK (3 μmol/mouse) in cottonseed oil (0.1 ml) once a week for eight consecutive weeks. Mice were fed either AIN-76A control diet or control diet containing p-XSC (10 ppm selenium), either during or after carcinogen administration. Dietary p-XSC significantly reduced lung tumor multiplicity, regardless of whether it was given during or after carcinogen administration. p-XSC was also an effective inhibitor of tumor development in the forestomach. To provide some biochemical insights into the protective role of p-XSC, its effect on selected phase I and II enzyme activities involved in the metabolism of NNK and B(a)P was also examined in vivo in this animal model. Dietary p-XSC significantly inhibited the activities of the phase I enzymes, methoxyresorufin O-dealkylase (MROD) and N-nitrosodimethylamine N-demethylase (NDMAD), in mouse liver, but it had no effect on ethoxyresorufin O-dealkylase (EROD), pentoxyresorufin O-dealkylase (PROD), and erythromycin N-demethylase (ERYTD). Total glutathione S-transferase (GST) enzyme activity, as well as GST-π and GST-μ enzyme activities, were significantly induced by dietary p-XSC in both the lung and liver. Glutathione peroxidase (GPX) activity was also induced by p-XSC in mouse lung, but not in the liver. Dietary p-XSC had no effect on selenium-dependent glutathione peroxidase (GPXSe), GST-α, and UDP-glucuronosyl transferase (UDPGT) enzyme activities in either the lung or the liver. These studies suggest that the chemopreventive efficacy of p-XSC, when fed during carcinogen administration, may be, in part, due to the inhibition of certain phase I enzymes involved in the metabolic activation of these carcinogens, and the induction of specific phase II enzymes involved in their detoxification. The mechanisms that account for the effect of p-XSC when fed after carcinogen administration remain to be determined.

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

  • an Organoselenium Compound improves behavioral endocrinal and neurochemical changes induced by corticosterone in mice
    Psychopharmacology, 2014
    Co-Authors: Cristiani F Bortolatto, Gilson Zeni, Suelen O Heck, Andre L Stein, Marta M M F Duarte, Cristina W Nogueira
    Abstract:

    Rationale 3-(4-Fluorophenylselenyl)-2,5-diphenylselenophene (F-DPS) is a promising Organoselenium Compound that shows antidepressant-like properties related to interaction with the serotonergic system.

  • 2 2 dithienyl diselenide an Organoselenium Compound elicits antioxidant action and inhibits monoamine oxidase activity in vitro
    Journal of Enzyme Inhibition and Medicinal Chemistry, 2013
    Co-Authors: Cristiani F Bortolatto, Gilson Zeni, Pietro M. Chagas, Ethel A. Wilhelm, Cristina W Nogueira
    Abstract:

    CONTEXT: Organoselenium Compounds have been described as antioxidant and neuroprotective agents. OBJECTIVE: To evaluate the antioxidant action of 2,2'-dithienyl diselenide (DTDS) and its effects in brain monoamine oxidase (MAO) activity in vitro. MATERIALS AND METHODS: Assays for reactive species (RS), lipid peroxidation, protein oxidation, MAO A and B activities in rat brain homogenate as well as mimetic dehydroascorbate reductase and glutathione S-transferase activities were performed using DTDS (μM range). RESULTS: DTDS was effective in decreasing the levels of RS as well as lipid peroxidation induced by malonate, sodium nitroprusside or FeCl₂/EDTA and protein carbonyl in the rat brain homogenate. DTDS elicited dehydroascorbate reductase-like and glutathione S-transferase-like activities. DTDS was effective in inhibiting both MAO-A and MAO-B activities. DISCUSSION: The results demonstrated that DTDS is an antioxidant agent with non-selective inhibitory effect on MAO activity. CONCLUSION: DTDS is a promising molecule to be evaluated in experimental models of neurological diseases.

  • p-Chloro-diphenyl diselenide, an Organoselenium Compound, with antidepressant-like and memory enhancer actions in aging male rats
    Biogerontology, 2012
    Co-Authors: Cristiani F Bortolatto, Pietro M. Chagas, Ethel A. Wilhelm, Cristina W Nogueira
    Abstract:

    The aim of this study was to evaluate the protective effects of p -chloro-diphenyl diselenide ( p -ClPhSe)_2 on depressant-like action and cognitive impairment caused by aging in male rats. For this purpose, old rats were orally treated with ( p -ClPhSe)_2 (10 or 25 mg/kg) for seven days. Then, rats were tested in experimental models of ambulation, memory and depression. In addition, Na^+ K^+ ATPase activity and reactive species (RS) levels were measured in rat cortex and hippocampus. Our findings demonstrated that treatment of old rats with ( p -ClPhSe)_2 (10 and 25 mg/kg) reversed spatial memory deficit in the object location test and depressant-like action in the forced swimming test (FST) caused by aging. Reduction in exploratory behavior (rearings) in the open-field test caused by aging was not altered by ( p -ClPhSe)_2 administration. Moreover, the increase of RS levels and inhibition of Na^+ K^+ ATPase activity in cortex and hippocampus resulting from aging were restored by the highest dose of ( p -ClPhSe)_2. To assess the mechanisms involved in the antidepressant-like effect of ( p -ClPhSe)_2, old rats received WAY100635 (0.1 mg/kg, subcutaneous, a selective 5-HT_1AR antagonist), ritanserin (1 mg/kg, intraperitoneal, a 5-HT_2A/2CR antagonist) or ondansetron (1 mg/kg, intraperitoneal, a 5-HT_3R antagonist) 15 min before ( p -ClPhSe)_2 (25 mg/kg) treatment. After 30 min, the FST was performed. Results showed that in addition to the antioxidant action, the modulation of 5-HT_1A and 5-HT_3 receptors may be at least partly involved in the antidepressant-like action elicited by ( p -ClPhSe)_2 in old rats. These findings highlight the beneficial potential of ( p -ClPhSe)_2 in aged male rats.

  • 2,2′-dithienyl diselenide, an Organoselenium Compound, elicits antioxidant action and inhibits monoamine oxidase activity in vitro
    Journal of Enzyme Inhibition and Medicinal Chemistry, 2012
    Co-Authors: Cristiani F Bortolatto, Gilson Zeni, Pietro M. Chagas, Ethel A. Wilhelm, Cristina W Nogueira
    Abstract:

    CONTEXT: Organoselenium Compounds have been described as antioxidant and neuroprotective agents. OBJECTIVE: To evaluate the antioxidant action of 2,2'-dithienyl diselenide (DTDS) and its effects in brain monoamine oxidase (MAO) activity in vitro. MATERIALS AND METHODS: Assays for reactive species (RS), lipid peroxidation, protein oxidation, MAO A and B activities in rat brain homogenate as well as mimetic dehydroascorbate reductase and glutathione S-transferase activities were performed using DTDS (μM range). RESULTS: DTDS was effective in decreasing the levels of RS as well as lipid peroxidation induced by malonate, sodium nitroprusside or FeCl₂/EDTA and protein carbonyl in the rat brain homogenate. DTDS elicited dehydroascorbate reductase-like and glutathione S-transferase-like activities. DTDS was effective in inhibiting both MAO-A and MAO-B activities. DISCUSSION: The results demonstrated that DTDS is an antioxidant agent with non-selective inhibitory effect on MAO activity. CONCLUSION: DTDS is a promising molecule to be evaluated in experimental models of neurological diseases.

  • protective effect of binaphthyl diselenide a synthetic Organoselenium Compound on 2 nitropropane induced hepatotoxicity in rats
    Cell Biochemistry and Function, 2010
    Co-Authors: Mohammad Ibrahim, Waseem Hassan, Cristina W Nogueira, Marina Prigol, Joao Rocha
    Abstract:

    Organoselenides have been documented as promising pharmacological agents against a number of diseases associated with oxidative stress. Here we have investigated, for the first time, the potential antioxidant activity of binaphthyl diselenide ((NapSe)2; 50 mg kg−1, p.o.) against the 2-nitropropane (2-NP)-induced hepatoxicity in rats, using different end points of toxicity (liver histopathology, plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatinine). In addition, in view of the association of oxidative stress with 2-NP exposure, hepatic lipid peroxidation, ascorbic acid levels, δ-aminolevulinate dehydratase (δ-ALA-D) and catalase (CAT) activities were evaluated. 2-NP caused an increase of AST, ALT and hepatic lipid peroxidation. 2-NP also caused hepatic histopathological alterations and δ-ALA-D inhibition. (NapSe)2 (50 mg kg−1) prevented 2-NP-induced changes in plasmatic ALT and AST activities and also prevented changes in hepatic histology, δ-ALA-D and lipid peroxidation. Results presented here indicate that the protective mechanism of (NapSe)2 against 2-NP hepatotoxicity is possibly linked to its antioxidant activity. Copyright © 2010 John Wiley & Sons, Ltd.

Mohammad Ibrahim - One of the best experts on this subject based on the ideXlab platform.

  • in vitro evaluation of glutathione peroxidase gpx like activity and antioxidant properties of an Organoselenium Compound
    Toxicology in Vitro, 2015
    Co-Authors: Mohammad Ibrahim, Anna Maria Deobald, Niaz Muhammad, Muhammad Naeem, Jean Paul Kamdem, Joao Rocha
    Abstract:

    Abstract The amine based diselenide, (Z)-N-(4-methylbenzylidene)-1-(2-((2-(1-((E)-4-methyl benzylideneamino)ethyl)phenyl)diselanyl)phenyl)ethanamine ethyl)phenyl) diselanyl) phenyl) ethylimino) methyl)phenol (Compound A) an Organoselenium Compound that can mimic endogenous antioxidant enzymes, such as glutathione peroxidase (GPx), and diphenyl diselenide (PhSe)2 were tested against lipid peroxidation induced by sodium nitroprusside (SNP) and Fe(II) in rat brain, interaction with 1,1-diphenyl-2-picrylhydrazyl stable free radical (DPPH) and glutathione peroxidase (GPx) like antioxidant activities with H 2 O 2 or tBuOOH as substrates and with PhSH as thiol co-substrates as well as their ability to oxidize thiols were evaluated. From this study, we concluded that Compound A catalyze the reduction of H 2 O 2 with thiol was ∼2-fold more active than (PhSe)2) in both tBuOOH and H 2 O 2 systems when PhSH was used as a substrate. (PhSe)2 exhibited an increased ability to oxidize thiols while Compound A was not a good substrate for the oxidation of thiol used namely DTT and Cystine and showed DPPH radical-scavenging activity, while (PhSe)2 did not present radical scavenging activity. Compound A (amine based diselenide) presented better antioxidant profiles than (PhSe)2 against lipid peroxidation. The results clear showed that nitrogen atom in the Compound A can have a profound effect on their pharmacological properties.

  • 1 2 2 2 1 aminoethyl phenyl diselanyl phenyl ethanamine an amino Organoselenium Compound with interesting antioxidant profile
    Toxicology in Vitro, 2014
    Co-Authors: Waseem Hassan, Mohammad Ibrahim, Anna Maria Deobald, Jean Paul Kamdem, Javed Anwar, Diogo O Souza
    Abstract:

    Abstract Free radical scavenging and antioxidant activities of 1-(2-(2-(2-(1-aminoethyl)phenyl)diselanyl)phenyl)ethanamine (Compound A) and diphenyl diselenide (PhSe)2 were examined and compared for inhibition of Fe(II) and sodium nitroprusside (SNP) stimulated lipid peroxidation in rat brain, interaction with 1,1-diphenyl-2-picrylhydrazyl (DPPH) stable free radical and their glutathione peroxidase (GPx) like antioxidant activities with H2O2 or tBuOOH as substrates and with PhSH as thiol co-substrates as well as their ability to oxidize mono- and di-thiols were also evaluated. This study revealed that an amino group in amino diselenide drastically enhances their catalytic activities in the aromatic thiol (PhSH) assay system. Compound A was ∼2-fold more active than (PhSe)2 in both tBuOOH and H2O2 assay systems. In addition, the present results showed that (PhSe)2 exhibited an increased ability to oxidize di-thiols, Compound A was not a good substrate for the oxidation of thiol used namely DTT, cystine and DMPS. The antioxidant potency against Fe(II) and SNP-induced brain TBARS were in this order [(Compound A); IC50 2 μM and 4 μM] > [(PhSe)2; IC50 19 μM and 27.5 μM. Compound A showed DPPH radical-scavenging activity. This study provides in vitro evidence anti-oxidant action of the tested Organoselenium Compounds, that the nitrogen atom in the organochalcogens can have a profound effect on their antioxidant activity.

  • protective effect of binaphthyl diselenide a synthetic Organoselenium Compound on 2 nitropropane induced hepatotoxicity in rats
    Cell Biochemistry and Function, 2010
    Co-Authors: Mohammad Ibrahim, Waseem Hassan, Cristina W Nogueira, Marina Prigol, Joao Rocha
    Abstract:

    Organoselenides have been documented as promising pharmacological agents against a number of diseases associated with oxidative stress. Here we have investigated, for the first time, the potential antioxidant activity of binaphthyl diselenide ((NapSe)2; 50 mg kg−1, p.o.) against the 2-nitropropane (2-NP)-induced hepatoxicity in rats, using different end points of toxicity (liver histopathology, plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatinine). In addition, in view of the association of oxidative stress with 2-NP exposure, hepatic lipid peroxidation, ascorbic acid levels, δ-aminolevulinate dehydratase (δ-ALA-D) and catalase (CAT) activities were evaluated. 2-NP caused an increase of AST, ALT and hepatic lipid peroxidation. 2-NP also caused hepatic histopathological alterations and δ-ALA-D inhibition. (NapSe)2 (50 mg kg−1) prevented 2-NP-induced changes in plasmatic ALT and AST activities and also prevented changes in hepatic histology, δ-ALA-D and lipid peroxidation. Results presented here indicate that the protective mechanism of (NapSe)2 against 2-NP hepatotoxicity is possibly linked to its antioxidant activity. Copyright © 2010 John Wiley & Sons, Ltd.

  • ph dependent fe ii pathophysiology and protective effect of an Organoselenium Compound
    FEBS Letters, 2009
    Co-Authors: Waseem Hassan, Mohammad Ibrahim, Anna Maria Deobald, Antonio L Braga, Cristina W Nogueira, Joao Rocha
    Abstract:

    Influence of pH on the extent of lipid peroxidation and the anti-oxidant potential of an Organoselenium Compound is explored. Acidosis increased the rate of lipid peroxidation both in the absence and presence of Fe (II) in rat's brain, kidney and liver homogenate and phospholipids extract from egg yolk. The Organoselenium Compound significantly protected lipids from peroxidation, both in the absence and presence of Fe (II). Changing the pH of the reaction medium did not alter the anti-oxidant activity of the tested Compound. This study provides in vitro evidence for acidosis-induced oxidative stress in brain, kidney, liver homogenate and phospholipids extract and the anti-oxidant action of the tested Organoselenium Compound.

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

  • in vitro evaluation of glutathione peroxidase gpx like activity and antioxidant properties of an Organoselenium Compound
    Toxicology in Vitro, 2015
    Co-Authors: Mohammad Ibrahim, Anna Maria Deobald, Niaz Muhammad, Muhammad Naeem, Jean Paul Kamdem, Joao Rocha
    Abstract:

    Abstract The amine based diselenide, (Z)-N-(4-methylbenzylidene)-1-(2-((2-(1-((E)-4-methyl benzylideneamino)ethyl)phenyl)diselanyl)phenyl)ethanamine ethyl)phenyl) diselanyl) phenyl) ethylimino) methyl)phenol (Compound A) an Organoselenium Compound that can mimic endogenous antioxidant enzymes, such as glutathione peroxidase (GPx), and diphenyl diselenide (PhSe)2 were tested against lipid peroxidation induced by sodium nitroprusside (SNP) and Fe(II) in rat brain, interaction with 1,1-diphenyl-2-picrylhydrazyl stable free radical (DPPH) and glutathione peroxidase (GPx) like antioxidant activities with H 2 O 2 or tBuOOH as substrates and with PhSH as thiol co-substrates as well as their ability to oxidize thiols were evaluated. From this study, we concluded that Compound A catalyze the reduction of H 2 O 2 with thiol was ∼2-fold more active than (PhSe)2) in both tBuOOH and H 2 O 2 systems when PhSH was used as a substrate. (PhSe)2 exhibited an increased ability to oxidize thiols while Compound A was not a good substrate for the oxidation of thiol used namely DTT and Cystine and showed DPPH radical-scavenging activity, while (PhSe)2 did not present radical scavenging activity. Compound A (amine based diselenide) presented better antioxidant profiles than (PhSe)2 against lipid peroxidation. The results clear showed that nitrogen atom in the Compound A can have a profound effect on their pharmacological properties.

  • protective effect of binaphthyl diselenide a synthetic Organoselenium Compound on 2 nitropropane induced hepatotoxicity in rats
    Cell Biochemistry and Function, 2010
    Co-Authors: Mohammad Ibrahim, Waseem Hassan, Cristina W Nogueira, Marina Prigol, Joao Rocha
    Abstract:

    Organoselenides have been documented as promising pharmacological agents against a number of diseases associated with oxidative stress. Here we have investigated, for the first time, the potential antioxidant activity of binaphthyl diselenide ((NapSe)2; 50 mg kg−1, p.o.) against the 2-nitropropane (2-NP)-induced hepatoxicity in rats, using different end points of toxicity (liver histopathology, plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatinine). In addition, in view of the association of oxidative stress with 2-NP exposure, hepatic lipid peroxidation, ascorbic acid levels, δ-aminolevulinate dehydratase (δ-ALA-D) and catalase (CAT) activities were evaluated. 2-NP caused an increase of AST, ALT and hepatic lipid peroxidation. 2-NP also caused hepatic histopathological alterations and δ-ALA-D inhibition. (NapSe)2 (50 mg kg−1) prevented 2-NP-induced changes in plasmatic ALT and AST activities and also prevented changes in hepatic histology, δ-ALA-D and lipid peroxidation. Results presented here indicate that the protective mechanism of (NapSe)2 against 2-NP hepatotoxicity is possibly linked to its antioxidant activity. Copyright © 2010 John Wiley & Sons, Ltd.

  • diphenyl diselenide a simple Organoselenium Compound decreases methylmercury induced cerebral hepatic and renal oxidative stress and mercury deposition in adult mice
    Brain Research Bulletin, 2009
    Co-Authors: Andressa Sausen De Freitas, Cristina W Nogueira, Vinicius Rafael Funck, Mariana Dos Santos Rotta, Denise Bohrer, Vanessa Morschbacher, Robson Puntel, Marcelo Farina, Michael Aschner, Joao Rocha
    Abstract:

    Abstract Oxidative stress has been pointed out as an important molecular mechanism in methylmercury (MeHg) intoxication. At low doses, diphenyl diselenide ((PhSe) 2 ), a structurally simple Organoselenium Compound, has been shown to possess antioxidant and neuroprotective properties. Here we have examined the possible in vivo protective effect of diphenyl diselenide against the potential pro-oxidative effects of MeHg in mouse liver, kidney, cerebrum and cerebellum. The effects of MeHg exposure (2 mg/(kg day) of methylmercury chloride 10 ml/kg, p.o .), as well as the possible antagonist effect of diphenyl diselenide (1 and 0.4 mg/(kg day); s.c. ) on body weight gain and on hepatic, cerebellar, cerebral and renal levels of thiobarbituric acid reactive substances (TBARS), non-protein thiols (NPSH), ascorbic acid content, mercury concentrations and activities of antioxidant enzymes (glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD)) were evaluated after 35 days of treatment. MeHg caused an increase in TBARS and decreased NPSH levels in all tissues. MeHg also induced a decrease in hepatic ascorbic acid content and in renal GPx and CAT activities. Diphenyl diselenide (1 mg/kg) conferred protection against MeHg-induced hepatic and renal lipid peroxidation and at both doses prevented the reduction in hepatic NPSH levels. Diphenyl diselenide also conferred a partial protection against MeHg-induced oxidative stress (TBARS and NPSH) in liver and cerebellum. Of particular importance, diphenyl diselenide decreased the deposition of Hg in cerebrum, cerebellum, kidney and liver. The present results indicate that diphenyl diselenide can protect against some toxic effects of MeHg in mice. This protection may be related to its antioxidant properties and its ability to reduce Hg body burden. We posit that formation of a selenol intermediate, which possesses high nucleophilicity and high affinity for MeHg, accounts for the ability of diphenyl diselenide to ameliorate MeHg-induced toxicity.

  • ph dependent fe ii pathophysiology and protective effect of an Organoselenium Compound
    FEBS Letters, 2009
    Co-Authors: Waseem Hassan, Mohammad Ibrahim, Anna Maria Deobald, Antonio L Braga, Cristina W Nogueira, Joao Rocha
    Abstract:

    Influence of pH on the extent of lipid peroxidation and the anti-oxidant potential of an Organoselenium Compound is explored. Acidosis increased the rate of lipid peroxidation both in the absence and presence of Fe (II) in rat's brain, kidney and liver homogenate and phospholipids extract from egg yolk. The Organoselenium Compound significantly protected lipids from peroxidation, both in the absence and presence of Fe (II). Changing the pH of the reaction medium did not alter the anti-oxidant activity of the tested Compound. This study provides in vitro evidence for acidosis-induced oxidative stress in brain, kidney, liver homogenate and phospholipids extract and the anti-oxidant action of the tested Organoselenium Compound.

  • antidepressant like effect of the Organoselenium Compound ebselen in mice evidence for the involvement of the monoaminergic system
    European Journal of Pharmacology, 2009
    Co-Authors: Thais Posser, Joao Rocha, Manuella P Kaster, Sara Cristiane Barauna, Ana Lucia S Rodrigues, Rodrigo B Leal
    Abstract:

    Abstract Ebselen [2-phenyl-1,2-benzisoselenazol-3(2H)-one] is a seleno-organic Compound which possesses a potent antioxidant activity and has been shown to exert neuroprotective effects in vitro and in vivo in a variety of pro-oxidative insults. The present study investigates a possible antidepressant activity of ebselen using two predictive tests for antidepressant activity in rodents: the forced swimming test and tail suspension test. Additionally, the mechanisms involved in the antidepressant-like effect of ebselen in mice were also assessed. Ebselen (10 mg/kg, s.c.) decreased the immobility time in the forced swimming test without accompanying changes in ambulation in the open-field test. In contrast, the administration of ebselen (10–30 mg/kg) did not produce any effect in the tail suspension test. The anti-immobility effect of ebselen (10 mg/kg, s.c.) was not prevented by pre-treatment of mice with p -chlorophenylalanine (PCPA, 100 mg/kg, i.p., an inhibitor of serotonin synthesis, 4 consecutive days), NAN-190 (0.5 mg/kg, i.p., a serotonin 5-HT 1A receptor antagonist) or ketanserin (5 mg/kg, i.p., a serotonin 5-HT 2A/2C receptor antagonist). On the other hand, the pre-treatment of mice with prazosin (1 mg/kg, i.p., an α 1 -adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an α 2 -adrenoceptor antagonist), SCH23390 (0.05 mg/kg, s.c., a dopamine D 1 receptor antagonist) or sulpiride (50 mg/kg, i.p., a dopamine D 2 receptor antagonist) completely blocked the antidepressant-like effect of ebselen (10 mg/kg, s.c.) in the forced swimming test. It may be concluded that ebselen produces an antidepressant-like effect in the forced swimming test that seems to be dependent on its interaction with the noradrenergic and dopaminergic systems, but not with the serotonergic system.

Huihui Zeng - One of the best experts on this subject based on the ideXlab platform.

  • the inhibitory effect of a novel Organoselenium Compound bbske on the tongue cancer tca8113 in vitro and in vivo
    Oral Oncology, 2008
    Co-Authors: Fengxia Xing, Huihui Zeng, Shenglin Li, Xiyuan Ge, Cunyu Wang, Dong Li, Ling Dong
    Abstract:

    Summary The aim of this study was to evaluate the anti-cancer effect of a novel Organoselenium Compound BBSKE (1,2-[bis(1,2-Benzisoselenazolone-3(2H)-ketone)]ethane, BBSKE, PCT: CN02/00412) on cell growth and apoptosis, focusing on the protein activity of Thioredoxin Reductase (TrxR) and Caspase-3, in oral squamous cell carcinoma (OSCC) in vitro and in vivo. Oral squamous cancer cell line Tca8113 was treated with various concentrations of BBSKE. Growth and apoptosis as well as the protein activities were analyzed. Morphologic changes of Tca8113 cells after 24 h treatment of BBSKE were determined by fluorescence microscopy. The increase of Caspase-3 activity and decrease of Thioredoxin reductase (TrxR) activity were also measured. BBSKE induced a significant cell growth inhibition and elicited typical apoptotic morphologic changes (chromatic condensation, nucleus fragmentation). This phenomenon was accompanied by a change in protein activity of Thioredoxin reductase (TrxR) and Caspase-3. The anti-cancer effect of BBSKE was then studied in well-established Tca8113 xenografts in nude mice. In those tumors, anti-cancer effects were observed and significantly higher than the controls. Together, these results indicate that BBSKE can inhibit tongue cancer cell proliferation in vitro and in vivo, and induce apoptosis in Tca8113 cell lines partially via inhibiting the activity of TrxR and promoting the activity of Caspase-3.

  • immune regulating activity of a novel Organoselenium Compound ethaselen 1 in c57 bl mice
    Journal of Peking University. Health sciences, 2006
    Co-Authors: Yirui Wang, Junjun Xiao, Xiaomin Dong, Shucong Meng, Shengju Deng, Bin Kuang, Fang Zhao, Huihui Zeng
    Abstract:

    OBJECTIVE: To detect the Immune regulating activity of ethaselen-1 (Eb1), a novel Organoselenium Compound, in C57/BL mice transplanted with Lewis lung cancer(LLC). METHODS: The LLC transplanted C57/BL mice models were established, and the mice was randomly divided into four groups, including high dose Eb1 group (25.0 mg/kg),low dose Eb1 group (12.5 mg/kg), positive control group (levamisole, LMS, 2.0 mg/kg) and negative control group(solvent). Intraperitoneal injections (ip.) of the four pharmaceuticals were performed once a day through the abdominal wall separately, from the second to the eighth day after cancer was transplanted. On the eleventh day, six mice of each group were killed and relative weight of spleen, transforming activity of spleen lymphocytes, NK cell activity, LAK cell activity and percentage of CD4(+)CD8(+)T lymphocyte were detect. RESULTS: Compared with the control group, high dose Eb1 could obviously increase the relative weight of spleen (150.59% and 122.55%), transforming activity of spleen lymphocytes(162.25% and 561.98%), NK cell activity(78.60% and 219.42%) and percentage of CD4(-)/CD8(+) T lymphocyte(104.72% and 105.87%) in normal mice and LLC mice. Compared with the control group, high dose Eb1 could also increase LAK cell activity of LLC mice by 195.11%. CONCLUSION: The novel Organoselenium Compound Eb1 has immune regulating activity in vivo.

  • Immune regulating activity of a novel Organoselenium Compound ethaselen-1 in C57/BL mice
    Journal of Peking University. Health sciences, 2006
    Co-Authors: Yirui Wang, Junjun Xiao, Xiaomin Dong, Shucong Meng, Shengju Deng, Bin Kuang, Fang Zhao, Huihui Zeng
    Abstract:

    OBJECTIVE: To detect the Immune regulating activity of ethaselen-1 (Eb1), a novel Organoselenium Compound, in C57/BL mice transplanted with Lewis lung cancer(LLC). METHODS: The LLC transplanted C57/BL mice models were established, and the mice was randomly divided into four groups, including high dose Eb1 group (25.0 mg/kg),low dose Eb1 group (12.5 mg/kg), positive control group (levamisole, LMS, 2.0 mg/kg) and negative control group(solvent). Intraperitoneal injections (ip.) of the four pharmaceuticals were performed once a day through the abdominal wall separately, from the second to the eighth day after cancer was transplanted. On the eleventh day, six mice of each group were killed and relative weight of spleen, transforming activity of spleen lymphocytes, NK cell activity, LAK cell activity and percentage of CD4(+)CD8(+)T lymphocyte were detect. RESULTS: Compared with the control group, high dose Eb1 could obviously increase the relative weight of spleen (150.59% and 122.55%), transforming activity of spleen lymphocytes(162.25% and 561.98%), NK cell activity(78.60% and 219.42%) and percentage of CD4(-)/CD8(+) T lymphocyte(104.72% and 105.87%) in normal mice and LLC mice. Compared with the control group, high dose Eb1 could also increase LAK cell activity of LLC mice by 195.11%. CONCLUSION: The novel Organoselenium Compound Eb1 has immune regulating activity in vivo.

  • induction of apoptosis in prostate cancer cell line pc 3 by bbske a novel Organoselenium Compound and its effect in vivo
    National Medical Journal of China, 2003
    Co-Authors: Huihui Zeng, Fengguang Yang, Hongwei Li, Xueqing Wu, Lizhang Yu
    Abstract:

    OBJECTIVE: To investigate the effects of BBSKE (1,2-[bis (1,2-benzisoselenazolone-3 (2H)-ketone)]ethane), a novel Organoselenium Compound, on the proliferation and apoptosis of the prostate cancer cell line PC-3, and to study its effect on the growth of prostate cancer in vivo. METHODS: Prostate cancer cells of the cell line PC-3 was cultivated in media with different concentrations of BBSKE and cisplatin. The inhibition of proliferation was measured by colorimetric MTT assay. The morphologic changes were observed by fluorescence microscopy, DNA fragmentation was visualized by agarose gel electrophoresis, and the DNA degradation was determined by flow cytometry. Western blot analysis was used to identify the expression of bcl-2 and bax. The activity of caspase-3 was determined by a micro-ELISA reader. Mouse prostate cancer cells of the TRAMP-C2 line were cultured and then injected subcutaneously into 2 male C57BL/6 mice to establish the animal model. Then the 2 mice were killed to collect the cancer cells. Twenty-four mice were injected intraperitoneally with single cell suspension of TRAMP-C2 cell and then divided into 3 groups of 8 mice undergoing intraperitoneal injection for 7 days: BBSKE group (BBSKE was administered at the dosage of 25mg/kg/day), cisplatin group (cisplatin 2mg/kg/d was injected), and control group (pure solvent was injected). Three weeks after the mice were killed and the tumors were taken out to calculate the inhibition rate. RESULTS: BBSKE inhibited the growth of the PC-3 cells dosage-dependently with a value of IC(50) of 17.90 micro mol/L after a 48 h exposure, higher than that in the case of cisplatin (15.00 micro mol/L). After exposure of PC-3 cells to BBSKE at the dosage of 20 micro mol/L for 48 hours the apoptosis rate was 26.32%, significantly higher than that of the control group (1.75%, P < 0.01). The expression of bcl-2 was decreased and the expression of bax remained almost unchanged along with the increase of BBSKE concentration. The activity of caspase 3 in the subgroup of BBSKE of the concentration of 5 micro mol/L remained almost unchanged, and was increased to 3.65 +/- 0.57 and 4.39 +/- 1.01 respectively in the BBSKE 10 micro mol/L and 20 micro mol/L subgroups, both significantly higher than that of the control group (both P < 0.05). In the in vivo experiment, the growth of tumor was significantly inhibited by BBSKE with an inhibition rate of 40% and the inhibition rate of the cisplatin group was 48%. CONCLUSION: The novel Organoselenium BBSKE inhibits the proliferation of PC-3 cell and promote its apoptosis, probably through downregulating the expression of bcl-2 and the activity of caspase-3. BBSKE also inhibits the growth of prostate cancer in vivo.

  • a novel Organoselenium Compound induces cell cycle arrest and apoptosis in prostate cancer cell lines
    Biochemical and Biophysical Research Communications, 2003
    Co-Authors: Lizhang Yu, Fengguang Yang, Huihui Zeng
    Abstract:

    Abstract Thioredoxin reductase (TrxR) in conjunction with thioredoxin (Trx) is a ubiquitous intracellular oxidoreductase system with antioxidant and redox regulatory roles. The properties of TrxR in combination with the functions of Trx position this system at the core of cellular thiol redox control and antioxidant defense. In some human tumors, the thioredoxin system is found over-expressed. Because of its role in stimulating cancer cell growth and as an inhibitor of apoptosis, the Trx system offers a target for the development of drugs to treat and prevent cancer. In a previous research, we successfully synthesized a novel Organoselenium Compound BBSKE(1,2-[bis(1,2-Benzisoselenazolone-3(2H)-ketone)]ethane, BBSKE, PCT: CN02/00412) targeting the TrxR, and it has demonstrated the inhibitory effect on the growth of a variety of human cancer cells from various organs. In this study, we investigated the inhibitory effect of BBSKE on TrxR activity in PC-3 and DU145 human prostate cancer cell lines, and its antitumoral effect on these two cell lines. Treatment of BBSKE inhibited the TrxR activity in both of the cell lines in a dose-dependent manner and it also inhibited the proliferation of these two cell lines in a dose-dependent manner. Cell cycle analysis showed S phase arrest in both of the cell lines following 48 h exposure to BBSKE. During the S arrest, analysis of cell cycle regulatory proteins demonstrated that BBSKE increased the protein levels of cyclinA, cyclinE, and P21, but decreased the levels of cyclinB1, cyclinD1, and Cdk4. Furthermore, BBSKE decreased the protein level of Bcl-2 but increased the level of Bax, and induced apoptosis in PC-3 and DU145 human prostate cancer cell lines. These results suggest that this novel TrxR inhibitor inhibits the proliferation of prostate cancer cells via S phase arrest and apoptosis in association with the regulation of multiple molecules in the cell cycle.