Cargando…
L-carnitine prevents lenvatinib-induced muscle toxicity without impairment of the anti-angiogenic efficacy
Lenvatinib is an oral tyrosine kinase inhibitor that acts on multiple receptors involved in angiogenesis. Lenvatinib is a standard agent for the treatment of several types of advanced cancers; however, it frequently causes muscle-related adverse reactions. Our previous study revealed that lenvatinib...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10116043/ https://www.ncbi.nlm.nih.gov/pubmed/37089945 http://dx.doi.org/10.3389/fphar.2023.1182788 |
_version_ | 1785028336750166016 |
---|---|
author | Jing, Zheng Iba, Tomohiro Naito, Hisamichi Xu, Pingping Morishige, Jun-ichi Nagata, Naoto Okubo, Hironao Ando, Hitoshi |
author_facet | Jing, Zheng Iba, Tomohiro Naito, Hisamichi Xu, Pingping Morishige, Jun-ichi Nagata, Naoto Okubo, Hironao Ando, Hitoshi |
author_sort | Jing, Zheng |
collection | PubMed |
description | Lenvatinib is an oral tyrosine kinase inhibitor that acts on multiple receptors involved in angiogenesis. Lenvatinib is a standard agent for the treatment of several types of advanced cancers; however, it frequently causes muscle-related adverse reactions. Our previous study revealed that lenvatinib treatment reduced carnitine content and the expression of carnitine-related and oxidative phosphorylation (OXPHOS) proteins in the skeletal muscle of rats. Therefore, this study aimed to evaluate the effects of L-carnitine on myotoxic and anti-angiogenic actions of lenvatinib. Co-administration of L-carnitine in rats treated with lenvatinib for 2 weeks completely prevented the decrease in carnitine content and expression levels of carnitine-related and OXPHOS proteins, including carnitine/organic cation transporter 2, in the skeletal muscle. Moreover, L-carnitine counteracted lenvatinib-induced protein synthesis inhibition, mitochondrial dysfunction, and cell toxicity in C2C12 myocytes. In contrast, L-carnitine had no influence on either lenvatinib-induced inhibition of vascular endothelial growth factor receptor 2 phosphorylation in human umbilical vein endothelial cells or angiogenesis in endothelial tube formation and mouse aortic ring assays. These results suggest that L-carnitine supplementation could prevent lenvatinib-induced muscle toxicity without diminishing its antineoplastic activity, although further clinical studies are needed to validate these findings. |
format | Online Article Text |
id | pubmed-10116043 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-101160432023-04-21 L-carnitine prevents lenvatinib-induced muscle toxicity without impairment of the anti-angiogenic efficacy Jing, Zheng Iba, Tomohiro Naito, Hisamichi Xu, Pingping Morishige, Jun-ichi Nagata, Naoto Okubo, Hironao Ando, Hitoshi Front Pharmacol Pharmacology Lenvatinib is an oral tyrosine kinase inhibitor that acts on multiple receptors involved in angiogenesis. Lenvatinib is a standard agent for the treatment of several types of advanced cancers; however, it frequently causes muscle-related adverse reactions. Our previous study revealed that lenvatinib treatment reduced carnitine content and the expression of carnitine-related and oxidative phosphorylation (OXPHOS) proteins in the skeletal muscle of rats. Therefore, this study aimed to evaluate the effects of L-carnitine on myotoxic and anti-angiogenic actions of lenvatinib. Co-administration of L-carnitine in rats treated with lenvatinib for 2 weeks completely prevented the decrease in carnitine content and expression levels of carnitine-related and OXPHOS proteins, including carnitine/organic cation transporter 2, in the skeletal muscle. Moreover, L-carnitine counteracted lenvatinib-induced protein synthesis inhibition, mitochondrial dysfunction, and cell toxicity in C2C12 myocytes. In contrast, L-carnitine had no influence on either lenvatinib-induced inhibition of vascular endothelial growth factor receptor 2 phosphorylation in human umbilical vein endothelial cells or angiogenesis in endothelial tube formation and mouse aortic ring assays. These results suggest that L-carnitine supplementation could prevent lenvatinib-induced muscle toxicity without diminishing its antineoplastic activity, although further clinical studies are needed to validate these findings. Frontiers Media S.A. 2023-04-06 /pmc/articles/PMC10116043/ /pubmed/37089945 http://dx.doi.org/10.3389/fphar.2023.1182788 Text en Copyright © 2023 Jing, Iba, Naito, Xu, Morishige, Nagata, Okubo and Ando. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Jing, Zheng Iba, Tomohiro Naito, Hisamichi Xu, Pingping Morishige, Jun-ichi Nagata, Naoto Okubo, Hironao Ando, Hitoshi L-carnitine prevents lenvatinib-induced muscle toxicity without impairment of the anti-angiogenic efficacy |
title | L-carnitine prevents lenvatinib-induced muscle toxicity without impairment of the anti-angiogenic efficacy |
title_full | L-carnitine prevents lenvatinib-induced muscle toxicity without impairment of the anti-angiogenic efficacy |
title_fullStr | L-carnitine prevents lenvatinib-induced muscle toxicity without impairment of the anti-angiogenic efficacy |
title_full_unstemmed | L-carnitine prevents lenvatinib-induced muscle toxicity without impairment of the anti-angiogenic efficacy |
title_short | L-carnitine prevents lenvatinib-induced muscle toxicity without impairment of the anti-angiogenic efficacy |
title_sort | l-carnitine prevents lenvatinib-induced muscle toxicity without impairment of the anti-angiogenic efficacy |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10116043/ https://www.ncbi.nlm.nih.gov/pubmed/37089945 http://dx.doi.org/10.3389/fphar.2023.1182788 |
work_keys_str_mv | AT jingzheng lcarnitinepreventslenvatinibinducedmuscletoxicitywithoutimpairmentoftheantiangiogenicefficacy AT ibatomohiro lcarnitinepreventslenvatinibinducedmuscletoxicitywithoutimpairmentoftheantiangiogenicefficacy AT naitohisamichi lcarnitinepreventslenvatinibinducedmuscletoxicitywithoutimpairmentoftheantiangiogenicefficacy AT xupingping lcarnitinepreventslenvatinibinducedmuscletoxicitywithoutimpairmentoftheantiangiogenicefficacy AT morishigejunichi lcarnitinepreventslenvatinibinducedmuscletoxicitywithoutimpairmentoftheantiangiogenicefficacy AT nagatanaoto lcarnitinepreventslenvatinibinducedmuscletoxicitywithoutimpairmentoftheantiangiogenicefficacy AT okubohironao lcarnitinepreventslenvatinibinducedmuscletoxicitywithoutimpairmentoftheantiangiogenicefficacy AT andohitoshi lcarnitinepreventslenvatinibinducedmuscletoxicitywithoutimpairmentoftheantiangiogenicefficacy |