The Experts below are selected from a list of 36510 Experts worldwide ranked by ideXlab platform

Viviane Glaser - One of the best experts on this subject based on the ideXlab platform.

  • Diphenyl diselenide administration enhances cortical mitochondrial number and activity by increasing hemeoxygenase type 1 content in a methylmercury-induced neuroToxicity mouse model
    Molecular and Cellular Biochemistry, 2014
    Co-Authors: Viviane Glaser, João Batista Teixeira Rocha, Marcos Raniel Straliotto, Roberta De Paula Martins, Ana Julia Hoffmann Vieira, Eliana De Medeiros Oliveira, Jorge Humberto Mukdsi, Alicia Inés Torres, Marcelo Farina, Ana Lucia De Paul
    Abstract:

    Interest in biochemistry of organoselenium compound has increased in the last decades, mainly due to their chemical and biological activities. Here, we investigated the protective effect of diphenyl diselenide (PhSe)_2 (5 μmol/kg), in a mouse model of methylmercury (MeHg)-induced Brain Toxicity. Swiss male mice were divided into four experimental groups: control, (PhSe)_2 (5 μmol/kg, subcutaneous administration), MeHg (40 mg/L, in tap water), and MeHg + (PhSe)_2. After the treatment (21 days), the animals were killed and the cerebral cortex was analyzed. Electron microscopy indicated an enlarged and fused mitochondria leading to a reduced number of organelles, in the MeHg-exposed mice. Furthermore, cortical creatine kinase activity, a sensitive mitochondrial oxidative stress sensor, was almost abolished by MeHg. Subcutaneous (PhSe)_2 co-treatment rescued from MeHg-induced mitochondrial alterations. (PhSe)_2 also behaved as an enhancer of mitochondrial biogenesis, by increasing cortical mitochondria content in mouse-receiving (PhSe)_2 alone. Mechanistically, (PhSe)_2 (1 μM; 24 h) would trigger the cytoprotective Nrf-2 pathway for activating target genes, since astroglial cells exposed to the chalcogen showed increased content of hemeoxygenase type 1, a sensitive marker of the activation of this via. Thus, it is proposed that the (PhSe)_2-neuroprotective effect might be linked to its mitoprotective activity.

  • protective effects of diphenyl diselenide in a mouse model of Brain Toxicity
    Chemico-Biological Interactions, 2013
    Co-Authors: Viviane Glaser, Bettina Moritz, Ariana Ern Schmitz, Alcir Luiz Dafre, Evelise Maria Nazari, Yara Maria Rauh Muller, Luciane Rosa Feksa, Marcos Raniel Straliottoa, Andreza Fabro De Bem, Marcelo Farina
    Abstract:

    Abstract Interest in organoselenide chemistry and biochemistry has increased in the past three decades, mainly due to their chemical and biological activities. Here, we investigated the protective effect of the organic selenium compound diphenyl diselenide (PhSe) 2 (5 μmol/kg), in a mouse model of methylmercury (MeHg)-induced Brain Toxicity. Our group has previously demonstrated that the oral and repeated administration (21 days) of MeHg (40 mg/L) induced MeHg Brain accumulation at toxic concentrations, and a pattern of severe cortical and cerebellar biochemical and behavioral. In order to assess neuroToxicity, the neurochemical parameters, namely, mitochondrial complexes I, II, II–III and IV, glutathione peroxidase (GPx) and glutathione reductase (GR) activities, the content of thiobarbituric acid-reactive substances (TBA-RS), 8-hydroxy-2′-deoxyguanosine (8-OHdG), and Brain-derived neurotrophic factor (BDNF), as well as, metal deposition were investigated in mouse cerebral cortex. Cortical neuroToxicity induced by Brain MeHg deposition was characterized by the reduction of complexes I, II, and IV activities, reduction of GPx and increased GR activities, increased TBA-RS and 8-OHdG content, and reduced BDNF levels. The daily treatment with (PhSe) 2 was able to counteract the inhibitory effect of MeHg on mitochondrial activities, the increased oxidative stress parameters, TBA-RS and 8-OHdG levels, and the reduction of BDNF content. The observed protective (PhSe) 2 effect could be linked to its antioxidant properties and/or its ability to reduce MeHg deposition in Brain, which was here histochemically corroborated. Altogether, these data indicate that (PhSe) 2 could be consider as a neuroprotectant compound to be tested under neuroToxicity.

Marcelo Farina - One of the best experts on this subject based on the ideXlab platform.

  • Diphenyl diselenide administration enhances cortical mitochondrial number and activity by increasing hemeoxygenase type 1 content in a methylmercury-induced neuroToxicity mouse model
    Molecular and Cellular Biochemistry, 2014
    Co-Authors: Viviane Glaser, João Batista Teixeira Rocha, Marcos Raniel Straliotto, Roberta De Paula Martins, Ana Julia Hoffmann Vieira, Eliana De Medeiros Oliveira, Jorge Humberto Mukdsi, Alicia Inés Torres, Marcelo Farina, Ana Lucia De Paul
    Abstract:

    Interest in biochemistry of organoselenium compound has increased in the last decades, mainly due to their chemical and biological activities. Here, we investigated the protective effect of diphenyl diselenide (PhSe)_2 (5 μmol/kg), in a mouse model of methylmercury (MeHg)-induced Brain Toxicity. Swiss male mice were divided into four experimental groups: control, (PhSe)_2 (5 μmol/kg, subcutaneous administration), MeHg (40 mg/L, in tap water), and MeHg + (PhSe)_2. After the treatment (21 days), the animals were killed and the cerebral cortex was analyzed. Electron microscopy indicated an enlarged and fused mitochondria leading to a reduced number of organelles, in the MeHg-exposed mice. Furthermore, cortical creatine kinase activity, a sensitive mitochondrial oxidative stress sensor, was almost abolished by MeHg. Subcutaneous (PhSe)_2 co-treatment rescued from MeHg-induced mitochondrial alterations. (PhSe)_2 also behaved as an enhancer of mitochondrial biogenesis, by increasing cortical mitochondria content in mouse-receiving (PhSe)_2 alone. Mechanistically, (PhSe)_2 (1 μM; 24 h) would trigger the cytoprotective Nrf-2 pathway for activating target genes, since astroglial cells exposed to the chalcogen showed increased content of hemeoxygenase type 1, a sensitive marker of the activation of this via. Thus, it is proposed that the (PhSe)_2-neuroprotective effect might be linked to its mitoprotective activity.

  • protective effects of diphenyl diselenide in a mouse model of Brain Toxicity
    Chemico-Biological Interactions, 2013
    Co-Authors: Viviane Glaser, Bettina Moritz, Ariana Ern Schmitz, Alcir Luiz Dafre, Evelise Maria Nazari, Yara Maria Rauh Muller, Luciane Rosa Feksa, Marcos Raniel Straliottoa, Andreza Fabro De Bem, Marcelo Farina
    Abstract:

    Abstract Interest in organoselenide chemistry and biochemistry has increased in the past three decades, mainly due to their chemical and biological activities. Here, we investigated the protective effect of the organic selenium compound diphenyl diselenide (PhSe) 2 (5 μmol/kg), in a mouse model of methylmercury (MeHg)-induced Brain Toxicity. Our group has previously demonstrated that the oral and repeated administration (21 days) of MeHg (40 mg/L) induced MeHg Brain accumulation at toxic concentrations, and a pattern of severe cortical and cerebellar biochemical and behavioral. In order to assess neuroToxicity, the neurochemical parameters, namely, mitochondrial complexes I, II, II–III and IV, glutathione peroxidase (GPx) and glutathione reductase (GR) activities, the content of thiobarbituric acid-reactive substances (TBA-RS), 8-hydroxy-2′-deoxyguanosine (8-OHdG), and Brain-derived neurotrophic factor (BDNF), as well as, metal deposition were investigated in mouse cerebral cortex. Cortical neuroToxicity induced by Brain MeHg deposition was characterized by the reduction of complexes I, II, and IV activities, reduction of GPx and increased GR activities, increased TBA-RS and 8-OHdG content, and reduced BDNF levels. The daily treatment with (PhSe) 2 was able to counteract the inhibitory effect of MeHg on mitochondrial activities, the increased oxidative stress parameters, TBA-RS and 8-OHdG levels, and the reduction of BDNF content. The observed protective (PhSe) 2 effect could be linked to its antioxidant properties and/or its ability to reduce MeHg deposition in Brain, which was here histochemically corroborated. Altogether, these data indicate that (PhSe) 2 could be consider as a neuroprotectant compound to be tested under neuroToxicity.

Ana Lucia De Paul - One of the best experts on this subject based on the ideXlab platform.

  • Diphenyl diselenide administration enhances cortical mitochondrial number and activity by increasing hemeoxygenase type 1 content in a methylmercury-induced neuroToxicity mouse model
    Molecular and Cellular Biochemistry, 2014
    Co-Authors: Viviane Glaser, João Batista Teixeira Rocha, Marcos Raniel Straliotto, Roberta De Paula Martins, Ana Julia Hoffmann Vieira, Eliana De Medeiros Oliveira, Jorge Humberto Mukdsi, Alicia Inés Torres, Marcelo Farina, Ana Lucia De Paul
    Abstract:

    Interest in biochemistry of organoselenium compound has increased in the last decades, mainly due to their chemical and biological activities. Here, we investigated the protective effect of diphenyl diselenide (PhSe)_2 (5 μmol/kg), in a mouse model of methylmercury (MeHg)-induced Brain Toxicity. Swiss male mice were divided into four experimental groups: control, (PhSe)_2 (5 μmol/kg, subcutaneous administration), MeHg (40 mg/L, in tap water), and MeHg + (PhSe)_2. After the treatment (21 days), the animals were killed and the cerebral cortex was analyzed. Electron microscopy indicated an enlarged and fused mitochondria leading to a reduced number of organelles, in the MeHg-exposed mice. Furthermore, cortical creatine kinase activity, a sensitive mitochondrial oxidative stress sensor, was almost abolished by MeHg. Subcutaneous (PhSe)_2 co-treatment rescued from MeHg-induced mitochondrial alterations. (PhSe)_2 also behaved as an enhancer of mitochondrial biogenesis, by increasing cortical mitochondria content in mouse-receiving (PhSe)_2 alone. Mechanistically, (PhSe)_2 (1 μM; 24 h) would trigger the cytoprotective Nrf-2 pathway for activating target genes, since astroglial cells exposed to the chalcogen showed increased content of hemeoxygenase type 1, a sensitive marker of the activation of this via. Thus, it is proposed that the (PhSe)_2-neuroprotective effect might be linked to its mitoprotective activity.

Favia Maria - One of the best experts on this subject based on the ideXlab platform.

  • Glufosinate constrains synchronous and metachronous metastasis by promoting anti‐tumor macrophages
    'EMBO', 2020
    Co-Authors: Menga Alessio, Serra Marina, Todisco Simona, Riera‐domingo Carla, Ammarah Ummi, Ehling Manuel, Palmieri, Erika M, Di Noia, Maria Antonietta, Gissi Rosanna, Favia Maria
    Abstract:

    Glutamine synthetase (GS) generates glutamine from glutamate and controls the release of inflammatory mediators. In macrophages, GS activity, driven by IL10, associates to the acquisition of M2-like functions. Conditional deletion of GS in macrophages inhibits metastasis by boosting the formation of anti-tumor, M1-like, tumor-associated macrophages (TAMs). From this basis, we evaluated the pharmacological potential of GS inhibitors in targeting metastasis, identifying glufosinate as a specific human GS inhibitor. Glufosinate was tested in both cultured macrophages and on mice bearing metastatic lung, skin and breast cancer. We found that glufosinate rewires macrophages toward an M1-like phenotype both at the primary tumor and metastatic site, countering immunosuppression and promoting vessel sprouting. This was also accompanied to a reduction in cancer cell intravasation and extravasation, leading to synchronous and metachronous metastasis growth inhibition, but no effects on primary tumor growth. Glufosinate treatment was well-tolerated, without liver and Brain Toxicity, nor hematopoietic defects. These results identify GS as a druggable enzyme to rewire macrophage functions and highlight the potential of targeting metabolic checkpoints in macrophages to treat cancer metastasis

  • Glufosinate constrains synchronous and metachronous metastasis by promoting anti-tumor macrophages
    'EMBO', 2020
    Co-Authors: Menga Alessio, Serra Marina, Todisco Simona, Ammarah Ummi, Ehling Manuel, Palmieri, Erika M, Gissi Rosanna, Riera-domingo Carla, Di Noia, Maria A, Favia Maria
    Abstract:

    Glutamine synthetase (GS) generates glutamine from glutamate and controls the release of inflammatory mediators. In macrophages, GS activity, driven by IL10, associates to the acquisition of M2-like functions. Conditional deletion of GS in macrophages inhibits metastasis by boosting the formation of anti-tumor, M1-like, tumor-associated macrophages (TAMs). From this basis, we evaluated the pharmacological potential of GS inhibitors in targeting metastasis, identifying glufosinate as a specific human GS inhibitor. Glufosinate was tested in both cultured macrophages and on mice bearing metastatic lung, skin and breast cancer. We found that glufosinate rewires macrophages toward an M1-like phenotype both at the primary tumor and metastatic site, countering immunosuppression and promoting vessel sprouting. This was also accompanied to a reduction in cancer cell intravasation and extravasation, leading to synchronous and metachronous metastasis growth inhibition, but no effects on primary tumor growth. Glufosinate treatment was well-tolerated, without liver and Brain Toxicity, nor hematopoietic defects. These results identify GS as a druggable enzyme to rewire macrophage functions and highlight the potential of targeting metabolic checkpoints in macrophages to treat cancer metastasis.status: publishe

Menga Alessio - One of the best experts on this subject based on the ideXlab platform.

  • Glufosinate constrains synchronous and metachronous metastasis by promoting anti‐tumor macrophages
    'EMBO', 2020
    Co-Authors: Menga Alessio, Serra Marina, Todisco Simona, Riera‐domingo Carla, Ammarah Ummi, Ehling Manuel, Palmieri, Erika M, Di Noia, Maria Antonietta, Gissi Rosanna, Favia Maria
    Abstract:

    Glutamine synthetase (GS) generates glutamine from glutamate and controls the release of inflammatory mediators. In macrophages, GS activity, driven by IL10, associates to the acquisition of M2-like functions. Conditional deletion of GS in macrophages inhibits metastasis by boosting the formation of anti-tumor, M1-like, tumor-associated macrophages (TAMs). From this basis, we evaluated the pharmacological potential of GS inhibitors in targeting metastasis, identifying glufosinate as a specific human GS inhibitor. Glufosinate was tested in both cultured macrophages and on mice bearing metastatic lung, skin and breast cancer. We found that glufosinate rewires macrophages toward an M1-like phenotype both at the primary tumor and metastatic site, countering immunosuppression and promoting vessel sprouting. This was also accompanied to a reduction in cancer cell intravasation and extravasation, leading to synchronous and metachronous metastasis growth inhibition, but no effects on primary tumor growth. Glufosinate treatment was well-tolerated, without liver and Brain Toxicity, nor hematopoietic defects. These results identify GS as a druggable enzyme to rewire macrophage functions and highlight the potential of targeting metabolic checkpoints in macrophages to treat cancer metastasis

  • Glufosinate constrains synchronous and metachronous metastasis by promoting anti-tumor macrophages
    'EMBO', 2020
    Co-Authors: Menga Alessio, Serra Marina, Todisco Simona, Ammarah Ummi, Ehling Manuel, Palmieri, Erika M, Gissi Rosanna, Riera-domingo Carla, Di Noia, Maria A, Favia Maria
    Abstract:

    Glutamine synthetase (GS) generates glutamine from glutamate and controls the release of inflammatory mediators. In macrophages, GS activity, driven by IL10, associates to the acquisition of M2-like functions. Conditional deletion of GS in macrophages inhibits metastasis by boosting the formation of anti-tumor, M1-like, tumor-associated macrophages (TAMs). From this basis, we evaluated the pharmacological potential of GS inhibitors in targeting metastasis, identifying glufosinate as a specific human GS inhibitor. Glufosinate was tested in both cultured macrophages and on mice bearing metastatic lung, skin and breast cancer. We found that glufosinate rewires macrophages toward an M1-like phenotype both at the primary tumor and metastatic site, countering immunosuppression and promoting vessel sprouting. This was also accompanied to a reduction in cancer cell intravasation and extravasation, leading to synchronous and metachronous metastasis growth inhibition, but no effects on primary tumor growth. Glufosinate treatment was well-tolerated, without liver and Brain Toxicity, nor hematopoietic defects. These results identify GS as a druggable enzyme to rewire macrophage functions and highlight the potential of targeting metabolic checkpoints in macrophages to treat cancer metastasis.status: publishe