Yifan Xu, Jingfeng Huang, Huichuan Zhuang, Junqian Lin, Zhenzhou Jiang, Lixin Sun, Xin Huang, Luyong Zhang, Tao Wang
New Drug Screening and Pharmacodynamics Evaluation Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Gulou District, Nanjing, Jiangsu, 210009, China.
Pharmacology and Toxicology Laboratory, Grand Theravac Life Science (Nanjing) Co., Ltd, 699 Xuanwu Avenue, Xuanwu District, Nanjing, Jiangsu, 210018, China.
Toxicol Res (Camb). 2024 May 17;13(3):tfae073. doi: 10.1093/toxres/tfae073. eCollection 2024 Jun.
Picroside II (PII), an iridoid glycoside extracted from the rhizomes and stems of the genus Picroside, exhibits pronounced hepatoprotective properties. Pre-administration of PII protects against acute liver injury caused by D-galactosamine (D-Gal), carbon tetrachloride (CCl), and acetaminophen (APAP). This study aimed to elucidate the ramifications of PII administration subsequent to the initiation of acute hepatic injury.
Exploring the role of PII treatment in APAP-treated cell and rat models and in D-Gal and CCl-treated rat models.
In rats, APAP treatment increased serum aspartate transaminase, alanine transaminase, and alkaline phosphatase levels and decreased glutathione activity and the fluidity of the liver mitochondrial membrane. In L-02 cells, APAP exposure resulted in a decrement in membrane potential, an augmentation in the liberation of reactive oxygen species, and an acceleration of apoptotic processes. Moreover, PII pre-administration protected against D-Gal-induced acute hepatic injury and CCl-induced chronic hepatic injury in rodent models, whereas PII administration post-injury aggravated CCl-induced chronic hepatic injury.
Our results suggest that the effects of PII depend on the hepatic physiological or pathological state at the time of intervention. While PII possesses the potential to avert drug-induced acute hepatic injury through the mitigation of oxidative stress, its administration post-injury may exacerbate the hepatic damage, underscoring the critical importance of timing in therapeutic interventions.
胡黄连苷II（PII）是从胡黄连属植物的根茎和茎中提取的一种环烯醚萜苷，具有显著的肝脏保护特性。预先给予PII可预防由D-半乳糖胺（D-Gal）、四氯化碳（CCl）和对乙酰氨基酚（APAP）引起的急性肝损伤。本研究旨在阐明急性肝损伤发生后给予PII的后果。
探讨PII治疗在APAP处理的细胞和大鼠模型以及D-Gal和CCl处理的大鼠模型中的作用。
在大鼠中，APAP处理会增加血清天冬氨酸转氨酶、丙氨酸转氨酶和碱性磷酸酶水平，并降低谷胱甘肽活性和肝线粒体膜的流动性。在L-02细胞中，暴露于APAP会导致膜电位降低、活性氧释放增加以及凋亡过程加速。此外，预先给予PII可预防啮齿动物模型中D-Gal诱导的急性肝损伤和CCl诱导的慢性肝损伤，而损伤后给予PII会加重CCl诱导的慢性肝损伤。
我们的结果表明，PII的作用取决于干预时的肝脏生理或病理状态。虽然PII有潜力通过减轻氧化应激来避免药物诱导的急性肝损伤，但其在损伤后给予可能会加剧肝损伤，这突出了治疗干预中时机的至关重要性。
