Department of Medical Science, School of Medicine, Walailak University, Nakhon Si Thammarat 80160, Thailand.
Research Center in Tropical Pathobiology, Walailak University, Nakhon Si Thammarat 80160, Thailand.
Molecules. 2023 May 24;28(11):4294. doi: 10.3390/molecules28114294.
Doxorubicin (Dox) is one of the most frequently used chemotherapeutic drugs in a variety of cancers, but Dox-induced cardiotoxicity diminishes its therapeutic efficacy. The underlying mechanisms of Dox-induced cardiotoxicity are still not fully understood. More significantly, there are no established therapeutic guidelines for Dox-induced cardiotoxicity. To date, Dox-induced cardiac inflammation is widely considered as one of the underlying mechanisms involved in Dox-induced cardiotoxicity. The Toll-like receptor 4 (TLR4) signaling pathway plays a key role in Dox-induced cardiac inflammation, and growing evidence reports that TLR4-induced cardiac inflammation is strongly linked to Dox-induced cardiotoxicity. In this review, we outline and address all the available evidence demonstrating the involvement of the TLR4 signaling pathway in different models of Dox-induced cardiotoxicity. This review also discusses the effect of the TLR4 signaling pathway on Dox-induced cardiotoxicity. Understanding the role of the TLR4 signaling pathway in Dox-induced cardiac inflammation might be beneficial for developing a potential therapeutic strategy for Dox-induced cardiotoxicity.
多柔比星（Dox）是多种癌症中最常使用的化疗药物之一，但多柔比星诱导的心脏毒性降低了其治疗效果。多柔比星诱导的心脏毒性的潜在机制仍不完全清楚。更重要的是，目前还没有针对多柔比星诱导的心脏毒性的既定治疗指南。迄今为止，多柔比星诱导的心脏炎症被广泛认为是多柔比星诱导的心脏毒性的潜在机制之一。Toll 样受体 4（TLR4）信号通路在多柔比星诱导的心脏炎症中起关键作用，越来越多的证据表明，TLR4 诱导的心脏炎症与多柔比星诱导的心脏毒性密切相关。在这篇综述中，我们概述并讨论了所有现有的证据，这些证据表明 TLR4 信号通路参与了不同模型的多柔比星诱导的心脏毒性。本综述还讨论了 TLR4 信号通路对多柔比星诱导的心脏毒性的影响。了解 TLR4 信号通路在多柔比星诱导的心脏炎症中的作用可能有助于开发针对多柔比星诱导的心脏毒性的潜在治疗策略。
