Li Rong, Guo Chao, Wu Xinmou, Huang Zhaoquan, Chen Jian
Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guangxi, Guilin 541004, PR China.
Department of Pharmacy, Guigang City People's Hospital, The Eighth Affiliated Hospital of Guangxi Medical University, Guigang, Guangxi 537100, PR China.
Oncotarget. 2017 Jul 4;8(27):44440-44446. doi: 10.18632/oncotarget.17966.
Acetaminophen (APAP) is a common medication that induces hepatocellular damage in a time- or dose-dependent manner. Fibroblast growth factor 21 (FGF21) exerts a series of biological effects, including cellular repair. Compared to clinical diagnosis parameters, we aimed to evaluate whether FGF21 can serve as a sensitive biomarker for APAP-induced liver impairment. In the present study, we discussed comparable data from APAP-treated patients and parallelly established APAP-exposed mice for investigation. The resulting human serological data showed that APAP-treated patients have a visible reduction of FGF21 expression in undetected liver impairment of clinical diagnosis. In the animal study, APAP-exposed livers exhibited normal metabolic functions and liver functions, as revealed by biochemical test and histopathological examination. Endogenous FGF21 concentrations in APAP-treated mice were decreased in sera and liver cells. Moreover, comparable immunoassay data showed that hepatocellular FGF21 expression was reduced in a time-dependent manner. Taken together, these findings elucidate the involvement of abnormal FGF21 expression in early APAP-induced liver impairment. Interestingly, FGF21 may be a promising biomarker of APAP-exposed livers.
对乙酰氨基酚(APAP)是一种常见药物,可在时间或剂量依赖性方式下诱导肝细胞损伤。成纤维细胞生长因子21(FGF21)发挥一系列生物学作用,包括细胞修复。与临床诊断参数相比,我们旨在评估FGF21是否可作为APAP诱导的肝损伤的敏感生物标志物。在本研究中,我们讨论了来自APAP治疗患者的可比数据,并平行建立了APAP暴露小鼠进行研究。所得的人类血清学数据表明,在临床诊断未检测到肝损伤的情况下,APAP治疗患者的FGF21表达明显降低。在动物研究中,生化测试和组织病理学检查显示,APAP暴露的肝脏表现出正常的代谢功能和肝功能。APAP治疗小鼠血清和肝细胞中的内源性FGF21浓度降低。此外,可比的免疫测定数据表明,肝细胞FGF21表达呈时间依赖性降低。综上所述,这些发现阐明了FGF21异常表达在早期APAP诱导的肝损伤中的作用。有趣的是,FGF21可能是APAP暴露肝脏的一种有前景的生物标志物。