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在肝微环境中获得的药物和草药诱导肝损伤的损伤机制的见解。

Insights gained into the injury mechanism of drug and herb induced liver injury in the hepatic microenvironment.

机构信息

Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.

Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.

出版信息

Toxicology. 2024 Sep;507:153900. doi: 10.1016/j.tox.2024.153900. Epub 2024 Jul 29.

Abstract

Drug-Induced Liver Injury (DILI) and herb Induced Liver Injury (HILI) continues to pose a substantial challenge in both clinical practice and drug development, representing a grave threat to patient well-being. This comprehensive review introduces a novel perspective on DILI and HILI by thoroughly exploring the intricate microenvironment of the liver. The dynamic interplay among hepatocytes, sinusoidal endothelial cells, Kupffer cells, hepatic stellate cells, cholangiocytes, and the intricate vascular network assumes a central role in drug metabolism and detoxification. Significantly, this microenvironment is emerging as a critical determinant of susceptibility to DILI and HILI. The review delves into the multifaceted interactions within the liver microenvironment, providing valuable insights into the complex mechanisms that underlie DILI and HILI. Furthermore, we discuss potential strategies for mitigating drug-induced liver injury by targeting these influential factors, emphasizing their clinical relevance. By highlighting recent advances and future prospects, our aim is to shed light on the promising avenue of leveraging the liver microenvironment for the prevention and mitigation of DILI and HILI. This deeper understanding is crucial for advancing clinical practices and ensuring patient safety in the realm of DILI and HILI.

摘要

药物性肝损伤(DILI)和草药性肝损伤(HILI)仍然是临床实践和药物开发中的重大挑战,严重威胁着患者的健康。本综述通过深入探讨肝脏的复杂微环境,为 DILI 和 HILI 提供了一个新的视角。肝细胞、肝窦内皮细胞、枯否细胞、肝星状细胞、胆管细胞和复杂的血管网络之间的动态相互作用在药物代谢和解毒中起着核心作用。重要的是,这个微环境正成为易患 DILI 和 HILI 的关键决定因素。该综述深入探讨了肝脏微环境中的多方面相互作用,为 DILI 和 HILI 的复杂机制提供了有价值的见解。此外,我们还讨论了通过针对这些影响因素来减轻药物性肝损伤的潜在策略,强调了它们的临床相关性。通过强调最近的进展和未来的前景,我们的目的是揭示利用肝脏微环境预防和减轻 DILI 和 HILI 的有前途的途径。这种更深入的理解对于推进临床实践和确保 DILI 和 HILI 领域的患者安全至关重要。

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