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Effects of asparaginases and L-carnitine on Western-diet-induced hepatosteatosis in mice
Abstract Background: Asparaginases are common chemotherapeutic agents used for the treatment of acute lymphoblastic leukemia as a single or combinational therapy. Accompanying hepatotoxicity makes its use in elderly patients with pre-conditions, as obesity or other hepatopathies, difficult. Various...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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F1000 Research Limited
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10366552/ https://www.ncbi.nlm.nih.gov/pubmed/37497390 http://dx.doi.org/10.12688/f1000research.75870.1 |
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author | Ali Mahmoud Assar, Mona Hüffel, Martina Afify, Mamdouh Weiskirchen, Ralf Eisert, Albrecht Tolba, Rene Steitz, Julia |
author_facet | Ali Mahmoud Assar, Mona Hüffel, Martina Afify, Mamdouh Weiskirchen, Ralf Eisert, Albrecht Tolba, Rene Steitz, Julia |
author_sort | Ali Mahmoud Assar, Mona |
collection | PubMed |
description | Abstract Background: Asparaginases are common chemotherapeutic agents used for the treatment of acute lymphoblastic leukemia as a single or combinational therapy. Accompanying hepatotoxicity makes its use in elderly patients with pre-conditions, as obesity or other hepatopathies, difficult. Various hepatoprotective compounds like, L-carnitine, are discussed to ameliorate the induced hepatotoxicity. Methods: Here we aimed to establish a mouse model to study the effect of asparaginases (L-asparaginase and Oncaspar) and L-carnitine on Western-diet-induced hepatosteatosis in mice. Dose-escalation studies were performed to analyze asparaginases induced hepatotoxicity in C57BL/6 mice with normal or fatty livers. Subsequently, the effect of L-carnitine to improve the induced toxicity was tested. Results: Our results showed mild-to-moderate hepatotoxic effects while the Western-diet induced a higher degree of vacuolization and hepatocyte damage in liver tissue. Testing of L-carnitine in the established models did not show any protective effect on the toxicity or impairment of the efficacy of asparaginases. Conclusion: The here established models were able to demonstrate the asparaginase-induced hepatotoxic effects which were enhanced by the Western-diet. However, to test potential ameliorating drugs, the models might need some improvements. |
format | Online Article Text |
id | pubmed-10366552 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | F1000 Research Limited |
record_format | MEDLINE/PubMed |
spelling | pubmed-103665522023-07-26 Effects of asparaginases and L-carnitine on Western-diet-induced hepatosteatosis in mice Ali Mahmoud Assar, Mona Hüffel, Martina Afify, Mamdouh Weiskirchen, Ralf Eisert, Albrecht Tolba, Rene Steitz, Julia F1000Res Research Article Abstract Background: Asparaginases are common chemotherapeutic agents used for the treatment of acute lymphoblastic leukemia as a single or combinational therapy. Accompanying hepatotoxicity makes its use in elderly patients with pre-conditions, as obesity or other hepatopathies, difficult. Various hepatoprotective compounds like, L-carnitine, are discussed to ameliorate the induced hepatotoxicity. Methods: Here we aimed to establish a mouse model to study the effect of asparaginases (L-asparaginase and Oncaspar) and L-carnitine on Western-diet-induced hepatosteatosis in mice. Dose-escalation studies were performed to analyze asparaginases induced hepatotoxicity in C57BL/6 mice with normal or fatty livers. Subsequently, the effect of L-carnitine to improve the induced toxicity was tested. Results: Our results showed mild-to-moderate hepatotoxic effects while the Western-diet induced a higher degree of vacuolization and hepatocyte damage in liver tissue. Testing of L-carnitine in the established models did not show any protective effect on the toxicity or impairment of the efficacy of asparaginases. Conclusion: The here established models were able to demonstrate the asparaginase-induced hepatotoxic effects which were enhanced by the Western-diet. However, to test potential ameliorating drugs, the models might need some improvements. F1000 Research Limited 2022-02-01 /pmc/articles/PMC10366552/ /pubmed/37497390 http://dx.doi.org/10.12688/f1000research.75870.1 Text en Copyright: © 2022 Ali Mahmoud Assar M et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Ali Mahmoud Assar, Mona Hüffel, Martina Afify, Mamdouh Weiskirchen, Ralf Eisert, Albrecht Tolba, Rene Steitz, Julia Effects of asparaginases and L-carnitine on Western-diet-induced hepatosteatosis in mice |
title | Effects of asparaginases and L-carnitine on Western-diet-induced hepatosteatosis in mice |
title_full | Effects of asparaginases and L-carnitine on Western-diet-induced hepatosteatosis in mice |
title_fullStr | Effects of asparaginases and L-carnitine on Western-diet-induced hepatosteatosis in mice |
title_full_unstemmed | Effects of asparaginases and L-carnitine on Western-diet-induced hepatosteatosis in mice |
title_short | Effects of asparaginases and L-carnitine on Western-diet-induced hepatosteatosis in mice |
title_sort | effects of asparaginases and l-carnitine on western-diet-induced hepatosteatosis in mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10366552/ https://www.ncbi.nlm.nih.gov/pubmed/37497390 http://dx.doi.org/10.12688/f1000research.75870.1 |
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