| RRC ID |
74826
|
| 著者 |
Jing Z, Iba T, Naito H, Xu P, Morishige JI, Nagata N, Okubo H, Ando H.
|
| タイトル |
L-carnitine prevents lenvatinib-induced muscle toxicity without impairment of the anti-angiogenic efficacy.
|
| ジャーナル |
Front Pharmacol
|
| Abstract |
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.
|
| 巻・号 |
14
|
| ページ |
1182788
|
| 公開日 |
2023-1-1
|
| DOI |
10.3389/fphar.2023.1182788
|
| PII |
1182788
|
| PMID |
37089945
|
| PMC |
PMC10116043
|
| IF |
4.225
|
| リソース情報 |
| ヒト・動物細胞 |
C2C12(RCB0987) |
