Effect of combined sublethal X-ray irradiation and cyclosporine A treatment in NOD <i>scid</i> gamma (NSG) mice
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- Walcher Lia
- Fraunhofer Institute for Cell Therapy and Immunology, Perlickstrasse 1, 04103 Leipzig, Germany
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- Müller Claudia
- Fraunhofer Institute for Cell Therapy and Immunology, Perlickstrasse 1, 04103 Leipzig, Germany
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- Hilger Nadja
- Fraunhofer Institute for Cell Therapy and Immunology, Perlickstrasse 1, 04103 Leipzig, Germany Institute for Clinical Immunology, University of Leipzig, Johannisallee 30, 04103 Leipzig, Germany
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- Kretschmer Anna
- Fraunhofer Institute for Cell Therapy and Immunology, Perlickstrasse 1, 04103 Leipzig, Germany
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- Stahl Lilly
- Fraunhofer Institute for Cell Therapy and Immunology, Perlickstrasse 1, 04103 Leipzig, Germany
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- Wigge Simone
- Grünenthal GmbH, Zieglerstrasse 6, 52078 Aachen, Germany
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- Rengelshausen Jens
- Grünenthal GmbH, Zieglerstrasse 6, 52078 Aachen, Germany
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- Müller Anne M.
- Fraunhofer Institute for Cell Therapy and Immunology, Perlickstrasse 1, 04103 Leipzig, Germany
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- Fricke Stephan
- Fraunhofer Institute for Cell Therapy and Immunology, Perlickstrasse 1, 04103 Leipzig, Germany
Bibliographic Information
- Other Title
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- Effect of combined sublethal X-ray irradiation and cyclosporine A treatment in NOD scid gamma (NSG) mice
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Abstract
<p>Cyclosporine A (CsA) is used in hematopoietic stem cell transplantations (HSCT) to prevent graft-versus-host disease (GvHD). GvHD is the most severe side effect of allogeneic HSCT and efficient therapies are lacking. Mouse models are an essential tool for assessing potential new therapeutic strategies. Our aim is to mimic a clinical setting as close as possible using CsA treatment after sublethal irradiation in NSG mice and thereby evaluate the feasibility of this mouse model for GvHD studies. The effect of CsA (7.5 mg/kg body weight) on sublethally X-ray irradiated (2 Gy) and non-irradiated NSG mice was tested. CsA was administered orally every twelve hours for nine days. Animals irradiated and treated with CsA showed a shorter survival (n=3/10) than irradiated animals treated with NaCl (n=10/10). Furthermore, combined therapy resulted in severe weight loss (82 ± 6% of initial weight, n=7, day 8), with weight recovery after the CsA application was ceased. A high number of apoptotic events in the liver was observed in these mice (0.431 ± 0.371 apoptotic cells/cm2, n=2, compared to 0.027 ± 0.034 apoptotic cells/cm2, n=5, in the non-irradiated group). Other adverse effects, including a decrease in white blood cell counts were non-CsA-specific manifestations of irradiation. The combination of CsA treatment with irradiation has a hepatotoxic and lethal effect on NSG mice, whereas the treatment without irradiation is tolerated. Therefore, when using in vivo models of GvHD in NSG mice, a combined treatment with CsA and X-ray irradiation should be avoided or carefully evaluated.</p>
Journal
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- Experimental Animals
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Experimental Animals 68 (1), 1-11, 2019
Japanese Association for Laboratory Animal Science
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Details 詳細情報について
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- CRID
- 1390282763100415104
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- NII Article ID
- 130007604469
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- NII Book ID
- AA11032321
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- ISSN
- 18817122
- 00075124
- 13411357
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- NDL BIB ID
- 029481528
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- PubMed
- 30078790
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed