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Vijay K Singh - One of the best experts on this subject based on the ideXlab platform.

  • Alpha-Tocopherol Succinate- and AMD3100-mobilized progenitors mitigate radiation combined injury in mice
    Journal of radiation research, 2013
    Co-Authors: Vijay K Singh, Stephen Y. Wise, Oluseyi O. Fatanmi, Lindsay A. Beattie, Elizabeth J. Ducey, Thomas M. Seed
    Abstract:

    The purpose of this study was to elucidate the role of Alpha-Tocopherol Succinate (TS)- and AMD3100-mobilized progenitors in mitigating combined injury associated with acute radiation exposure in combination with secondary physical wounding. CD2F1 mice were exposed to high doses of cobalt-60 gamma-radiation and then transfused intravenously with 5 million peripheral blood mononuclear cells (PBMCs) from TS- and AMD3100-injected mice after irradiation. Within 1 h after irradiation, mice were exposed to secondary wounding. Mice were observed for 30 d after irradiation and cytokine analysis was conducted by multiplex Luminex assay at various time-points after irradiation and wounding. Our results initially demonstrated that transfusion of TS-mobilized progenitors from normal mice enhanced survival of acutely irradiated mice exposed 24 h prior to transfusion to supralethal doses (11.5–12.5 Gy) of 60Co gamma-radiation. Subsequently, comparable transfusions of TS-mobilized progenitors were shown to significantly mitigate severe combined injuries in acutely irradiated mice. TS administered 24 h before irradiation was able to protect mice against combined injury as well. Cytokine results demonstrated that wounding modulates irradiation-induced cytokines. This study further supports the conclusion that the infusion of TS-mobilized progenitor-containing PBMCs acts as a bridging therapy in radiation-combined-injury mice. We suggest that this novel bridging therapeutic approach involving the infusion of TS-mobilized hematopoietic progenitors following acute radiation exposure or combined injury might be applicable to humans.

  • Alpha-Tocopherol Succinate-mobilized progenitors improve intestinal integrity after whole body irradiation.
    International journal of radiation biology, 2013
    Co-Authors: Vijay K Singh, Stephen Y. Wise, Oluseyi O. Fatanmi, Elizabeth J. Ducey, Pankaj Singh, Ana Posarac, David L. Bolduc, Thomas B. Elliott, Thomas M. Seed
    Abstract:

    AbstractPurpose: The objective of this study was to elucidate the action of α-Tocopherol Succinate (TS)- and AMD3100-mobilized progenitors in mitigating radiation-induced injuries.Material and methods: CD2F1 mice were exposed to a high dose of radiation and then transfused intravenously with 5 million peripheral blood mononuclear cells (PBMC) from TS- and AMD3100-injected mice after irradiation. Intestinal and splenic tissues were harvested after irradiation and cells of those tissues were analyzed for markers of apoptosis and mitosis. Bacterial translocation from gut to heart, spleen, and liver in TS-treated and irradiated mice was evaluated by bacterial culture.Results: We observed that the infusion of PBMC from TS- and AMD3100-injected mice significantly inhibited apoptosis, increased cell proliferation in the analyzed tissues of recipient mice, and inhibited bacterial translocation to various organs compared to mice receiving cells from vehicle-mobilized cells. This study further supports our contenti...

  • Alpha-Tocopherol Succinate- and AMD3100-mobilized progenitors mitigate radiation combined injury in mice
    2013
    Co-Authors: Vijay K Singh, Stephen Y. Wise, Oluseyi O. Fatanmi, Lindsay A. Beattie, Elizabeth J. Ducey, Thomas M. Seed
    Abstract:

    The purpose of this study was to elucidate the role of Alpha-Tocopherol Succinate (TS)- and AMD3100-mobi-lized progenitors in mitigating combined injury associated with acute radiation exposure in combination with secondary physical wounding. CD2F1 mice were exposed to high doses of cobalt-60 gamma-radiation and then transfused intravenously with 5 million peripheral blood mononuclear cells (PBMCs) from TS- and AMD3100-injected mice after irradiation. Within 1 h after irradiation, mice were exposed to secondary wounding. Mice were observed for 30 d after irradiation and cytokine analysis was conducted by multiplex Luminex assay at various time-points after irradiation and wounding. Our results initially demonstrated that transfusion of TS-mobilized progenitors from normal mice enhanced survival of acutely irradiated mice exposed 24 h prior to transfusion to supralethal doses (11.5–12.5 Gy) of 60Co gamma-radiation. Subsequently, comparable transfusions of TS-mobilized progenitors were shown to significantly mitigate severe combined injuries in acutely irradiated mice. TS administered 24 h before irradiation was able to protect mice against combined injury as well. Cytokine results demonstrated that wounding modulates irradi-ation-induced cytokines. This study further supports the conclusion that the infusion of TS-mobilized progeni-tor-containing PBMCs acts as a bridging therapy in radiation-combined-injury mice. We suggest that this novel bridging therapeutic approach involving the infusion of TS-mobilized hematopoietic progenitors follow

  • Tocopherol Succinate: Modulation of Antioxidant Enzymes and Oncogene Expression, and Hematopoietic Recovery
    International journal of radiation oncology biology physics, 2010
    Co-Authors: Vijay K Singh, Darren S Brown, Vaishali I. Parekh, Tzu-cheg Kao, Steven R. Mog
    Abstract:

    Purpose: A class of naturally occurring isoforms of Tocopherol (tocols) was shown to have varying degrees of protection when administered before radiation exposure. We recently demonstrated that {Alpha}-Tocopherol Succinate (TS) is a potential radiation prophylactic agent. Our objective in this study was to further investigate the mechanism of action of TS in mice exposed to {sup 60}Co {gamma}-radiation. Methods and Materials: We evaluated the effects of TS on expression of antioxidant enzymes and oncogenes by quantitative RT-PCR in bone marrow cells of {sup 60}Co {gamma}-irradiated mice. Further, we tested the ability of TS to rescue and repopulate hematopoietic stem cells by analyzing bone marrow cellularity and spleen colony forming unit in spleen of TS-injected and irradiated mice. Results: Our results demonstrate that TS modulated the expression of antioxidant enzymes and inhibited expression of oncogenes in irradiated mice at different time points. TS also increased colony forming unit-spleen numbers and bone marrow cellularity in irradiated mice. Conclusions: Results provide additional support for the observed radioprotective efficacy of TS and insight into mechanisms.

  • Alpha Tocopherol Succinate protects mice from gamma radiation by induction of granulocyte colony stimulating factor
    International Journal of Radiation Biology, 2010
    Co-Authors: Vijay K Singh, Darren S Brown
    Abstract:

    Purpose: The purpose of this study was to further elucidate the role of granulocyte-colony stimulating factor (G-CSF)-induced in response to α-Tocopherol Succinate (TS) administration in protecting mice from total body irradiation (TBI).Material and methods: The dose, route, and schedule of TS administration for optimal G-CSF induction were determined by giving TS through subcutaneous (sc) and oral routes to male CD2F1 mice. The level of cytokine in serum was determined by multiplex Luminex. The role of G-CSF on survival after TBI was determined by first treating mice with a protective dose (400 mg/kg) of TS 24 h before exposure to a lethal dose (9.2 Gy, 0.6 Gy/min) of cobalt-60 γ-irradiation. The treated mice were then given neutralising antibody to G-CSF 16 h before TBI to abrogate the radioprotective efficacy of TS. The efficacy of whole blood samples obtained from TS-treated mice was evaluated to protect naive lethally irradiated mice. The hematopoietic stem cells in blood from TS-treated mice were an...

Mahnaz Badamchian - One of the best experts on this subject based on the ideXlab platform.

Chander Mohan Pathak - One of the best experts on this subject based on the ideXlab platform.

  • Enhancement in Alpha-Tocopherol Succinate-induced apoptosis by all-trans-retinoic acid in primary leukemic cells: role of antioxidant defense, Bax and c-myc
    Molecular and Cellular Biochemistry, 2008
    Co-Authors: Krishan Lal Khanduja, Surender Kumar, Pramod Kumar Avti, N. Varma, S. C. Varma, Chander Mohan Pathak
    Abstract:

    We investigated the possible mechanisms of All-trans retinoic acid (ATRA)-promoted apoptosis induced by α-Tocopherol Succinate (α-TS) in freshly isolated leukemic cells obtained from chronic myeloid leukemic patients. α-TS at 50 μM concentration significantly decreased superoxide dismutase (SOD) activity and reduced glutathione (GSH) by 29% and 25%, respectively, and increased lipid peroxidation level by 33%. Though 10 μM ATRA did not affect these parameters, it further significantly enhanced α-TS-induced changes. Bax expression in the leukemic cells was increased by treatment with ATRA, α-TS, and their combination to 40%, 240%, and 320%, respectively, without any change in Bcl2 and p53 expression. C-myc was down regulated by treatment with ATRA, α-TS and their combination to 22%, 48.5%, and 52%, respectively. In conclusion, the data reveal that enhancement of α-TS-induced apoptosis by ATRA in leukemic cells was through up regulation of Bax and lipid peroxidation, and down regulation of c-myc and GSH.

  • ATRA promotes Alpha Tocopherol Succinate-induced apoptosis in freshly isolated leukemic cells from chronic myeloid leukemic patients
    Molecular and Cellular Biochemistry, 2008
    Co-Authors: Surender Kumar, Krishan Lal Khanduja, Neelam Verma, Subhash C. Verma, Pramod Kumar Avti, Chander Mohan Pathak
    Abstract:

    We investigated the in vitro efficacy of all- trans retinoic acid (ATRA) and Alpha-Tocopherol Succinate (α-TS) alone and in combination on the induction of cell death in freshly isolated leukemic cells obtained from chronic myeloid leukemia (CML) patients. In vitro cytotoxicity and induction of lipid peroxidation by ATRA (10 μM) and α-TS (25 or 50 μM) were evaluated in primary leukemic cells by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and malondialdehyde formation respectively. Treatment of leukemic cells with α-TS alone or in combination with ATRA significantly ( P  

  • ATRA promotes Alpha Tocopherol Succinate-induced apoptosis in freshly isolated leukemic cells from chronic myeloid leukemic patients.
    Molecular and cellular biochemistry, 2007
    Co-Authors: Surender Kumar, Krishan Lal Khanduja, Neelam Verma, Subhash C. Verma, Pramod Kumar Avti, Chander Mohan Pathak
    Abstract:

    We investigated the in vitro efficacy of all-trans retinoic acid (ATRA) and Alpha-Tocopherol Succinate (Alpha-TS) alone and in combination on the induction of cell death in freshly isolated leukemic cells obtained from chronic myeloid leukemia (CML) patients. In vitro cytotoxicity and induction of lipid peroxidation by ATRA (10 microM) and Alpha-TS (25 or 50 microM) were evaluated in primary leukemic cells by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and malondialdehyde formation respectively. Treatment of leukemic cells with Alpha-TS alone or in combination with ATRA significantly (P < 0.05) decreased the cell viability in a concentration and time dependent manner as compared to peripheral blood mononuclear cells obtained from normal healthy controls. Lipid peroxidation was enhanced by 98% (P < 0.05) on combined treatment of cells with ATRA (10 microM) and Alpha-TS (50 microM). ATRA alone did not enhance the externalization of phosphatidyl serine as studied by annexin-V binding using fluorescence activated cell sorter analysis, whereas in combination with Alpha-TS it increased to 400% at 12 h. The treatment of leukemic cells to combination of ATRA with Alpha-TS significantly decreased (P < 0.05) mitochondrial membrane potential and enhanced lysosomal destabilization. The combination of these drugs also increased mitochondrial and cytosolic reactive oxygen species (ROS) production, nitric oxide levels, and caspase-3 activity significantly and caused DNA fragmentation at 24 h in a concentration dependent manner in the leukemic cells. Our data suggest that ATRA in combination with Alpha-TS efficiently induces apoptosis in leukemic cells, which may be a useful therapeutic modality in CML patients.

Thomas M. Seed - One of the best experts on this subject based on the ideXlab platform.

  • Alpha-Tocopherol Succinate- and AMD3100-mobilized progenitors mitigate radiation combined injury in mice
    Journal of radiation research, 2013
    Co-Authors: Vijay K Singh, Stephen Y. Wise, Oluseyi O. Fatanmi, Lindsay A. Beattie, Elizabeth J. Ducey, Thomas M. Seed
    Abstract:

    The purpose of this study was to elucidate the role of Alpha-Tocopherol Succinate (TS)- and AMD3100-mobilized progenitors in mitigating combined injury associated with acute radiation exposure in combination with secondary physical wounding. CD2F1 mice were exposed to high doses of cobalt-60 gamma-radiation and then transfused intravenously with 5 million peripheral blood mononuclear cells (PBMCs) from TS- and AMD3100-injected mice after irradiation. Within 1 h after irradiation, mice were exposed to secondary wounding. Mice were observed for 30 d after irradiation and cytokine analysis was conducted by multiplex Luminex assay at various time-points after irradiation and wounding. Our results initially demonstrated that transfusion of TS-mobilized progenitors from normal mice enhanced survival of acutely irradiated mice exposed 24 h prior to transfusion to supralethal doses (11.5–12.5 Gy) of 60Co gamma-radiation. Subsequently, comparable transfusions of TS-mobilized progenitors were shown to significantly mitigate severe combined injuries in acutely irradiated mice. TS administered 24 h before irradiation was able to protect mice against combined injury as well. Cytokine results demonstrated that wounding modulates irradiation-induced cytokines. This study further supports the conclusion that the infusion of TS-mobilized progenitor-containing PBMCs acts as a bridging therapy in radiation-combined-injury mice. We suggest that this novel bridging therapeutic approach involving the infusion of TS-mobilized hematopoietic progenitors following acute radiation exposure or combined injury might be applicable to humans.

  • Alpha-Tocopherol Succinate-mobilized progenitors improve intestinal integrity after whole body irradiation.
    International journal of radiation biology, 2013
    Co-Authors: Vijay K Singh, Stephen Y. Wise, Oluseyi O. Fatanmi, Elizabeth J. Ducey, Pankaj Singh, Ana Posarac, David L. Bolduc, Thomas B. Elliott, Thomas M. Seed
    Abstract:

    AbstractPurpose: The objective of this study was to elucidate the action of α-Tocopherol Succinate (TS)- and AMD3100-mobilized progenitors in mitigating radiation-induced injuries.Material and methods: CD2F1 mice were exposed to a high dose of radiation and then transfused intravenously with 5 million peripheral blood mononuclear cells (PBMC) from TS- and AMD3100-injected mice after irradiation. Intestinal and splenic tissues were harvested after irradiation and cells of those tissues were analyzed for markers of apoptosis and mitosis. Bacterial translocation from gut to heart, spleen, and liver in TS-treated and irradiated mice was evaluated by bacterial culture.Results: We observed that the infusion of PBMC from TS- and AMD3100-injected mice significantly inhibited apoptosis, increased cell proliferation in the analyzed tissues of recipient mice, and inhibited bacterial translocation to various organs compared to mice receiving cells from vehicle-mobilized cells. This study further supports our contenti...

  • Alpha-Tocopherol Succinate- and AMD3100-mobilized progenitors mitigate radiation combined injury in mice
    2013
    Co-Authors: Vijay K Singh, Stephen Y. Wise, Oluseyi O. Fatanmi, Lindsay A. Beattie, Elizabeth J. Ducey, Thomas M. Seed
    Abstract:

    The purpose of this study was to elucidate the role of Alpha-Tocopherol Succinate (TS)- and AMD3100-mobi-lized progenitors in mitigating combined injury associated with acute radiation exposure in combination with secondary physical wounding. CD2F1 mice were exposed to high doses of cobalt-60 gamma-radiation and then transfused intravenously with 5 million peripheral blood mononuclear cells (PBMCs) from TS- and AMD3100-injected mice after irradiation. Within 1 h after irradiation, mice were exposed to secondary wounding. Mice were observed for 30 d after irradiation and cytokine analysis was conducted by multiplex Luminex assay at various time-points after irradiation and wounding. Our results initially demonstrated that transfusion of TS-mobilized progenitors from normal mice enhanced survival of acutely irradiated mice exposed 24 h prior to transfusion to supralethal doses (11.5–12.5 Gy) of 60Co gamma-radiation. Subsequently, comparable transfusions of TS-mobilized progenitors were shown to significantly mitigate severe combined injuries in acutely irradiated mice. TS administered 24 h before irradiation was able to protect mice against combined injury as well. Cytokine results demonstrated that wounding modulates irradi-ation-induced cytokines. This study further supports the conclusion that the infusion of TS-mobilized progeni-tor-containing PBMCs acts as a bridging therapy in radiation-combined-injury mice. We suggest that this novel bridging therapeutic approach involving the infusion of TS-mobilized hematopoietic progenitors follow

  • Induction of cytokines by radioprotective Tocopherol analogs.
    Experimental and molecular pathology, 2006
    Co-Authors: Vijay K Singh, Thomas M. Seed, Randi L. Shafran, William E. Jackson, K. Sree Kumar
    Abstract:

    Tocols are a family of eight isomers consisting of four Tocopherols and four tocotrienols that exist in four isomeric forms: Alpha (Alpha), beta (beta), gamma (gamma), and delta (delta). Recently, tocols were found to have important and unique biological effects on nutrition and health other than antioxidant properties and are, therefore, now receiving increased attention. We have demonstrated the radioprotective efficacy of various tocol analogs and some of their esters. Three forms of tocols - Alpha-Tocopherol, Alpha-Tocopherol Succinate, and gamma-tocotrienol - significantly protected mice against lethal gamma irradiation when administered subcutaneously 24 h before irradiation. The radioprotective effects of tocols on survival were associated with peripheral blood cell recovery after radiation induced cytopenia. Hematopoietic cytokines are known to promote the proliferation and differentiation of blood cell progenitors. Therefore, we hypothesized that peripheral blood cell recovery is preceded by hematopoietic cytokine induction. To test this hypothesis and compare the various radioprotective and non-radioprotective analogs, we measured serum cytokines using a sandwich ELISA, Luminex, and cytokine array in mice treated with various tocols (Alpha-Tocopherol Succinate, Alpha-Tocopherol, delta-Tocopherol, gamma- Tocopherol, gamma-tocotrienol, and Tocopherol acetate). Among the serum cytokines measured, ELISA and Luminex studies indicated that Alpha-Tocopherol, Alpha-Tocopherol Succinate, and gamma-tocotrienol increased G-CSF levels in mice. Alpha-Tocopherol Succinate was most effective in stimulating G-CSF. IL-6 was detected by Luminex in sera samples from mice treated with the above three analogs. The results of the cytokine array suggest that other cytokines and chemokines in addition to G-CSF and IL-6 are induced. Since G-CSF, IL-6, and certain chemokines are important hematopoietic factors, these results support our hypothesis that the protection of mice from radiation-induced hematopoietic death is mediated by cytokines and chemokines. These studies may indicate that Alpha-Tocopherol Succinate can be used as an adjunct in cancer chemotherapy, where neutropenia is a serious problem with threatening infectious complications.

  • Radiation Protection by the Antioxidant Alpha-Tocopherol Succinate
    2005
    Co-Authors: Vijay K Singh, Venkataraman Srinivasan, Raymond Toles, Patience Karikari, Thomas M. Seed, Konstantinos A. Papas, John A. Hyatt, Kapil Kumar
    Abstract:

    Abstract : Radiological terrorism and use of nuclear weapons are major concerns for national defense and homeland security. At low doses of radiation, the hazards from these scenarios may not be apparent immediately, but may result in late arising pathologies like cancer and pulmonary fibrosis. At high doses, the hazards vary from incapacitation due to nausea and diarrhea to mortality. Free radical species of oxygen, derived from the interaction of ionizing radiation with critical biological targets and with the aqueous cellular milieu, are implicated in these hazards. Scavengers of free radicals have been shown to be effective protectors from radiation damage. However, many of these protectors are either toxic or cannot be administered orally at doses that are effective. The data presented here indicate that Alpha-Tocopherol Succinate (TS), a free radical scavenger, can be used as a radioprotector with low toxicity. Tocopherol Succinate was dispersed in a vehicle containing polyethylene glycol-400 (PEG) and given orally (PO) to male CD2F1 mice. About 22-24 hours later, they were irradiated at different doses of 60Co radiation at a dose rate of 0.6 Gy/min. To maximize the protection, different formulations of the vehicle were used. Mice were monitored for body weight and survival for 30 days. In vitro experiments were done to study the effects of TS on radiation-induced apoptosis of Jurkat cells (lymphoblastoid cell line) using flow cytometry. Although different formulations for solubilizing TS were used, oral formulations based on PEG were found to provide better protection than those based on oil emulsions. The best protection was obtained with a combination of PEG-400 and an emulsifier consisted of benzyl alcohol and ethyl alcohol.

Allan L. Goldstein - One of the best experts on this subject based on the ideXlab platform.