Department of Physics, National Taiwan University, Taipei, Taiwan, Republic of China.
School of Engineering and Applied Physics, Cornell University, Ithaca, New York.
J Biophotonics. 2019 Mar;12(3):e201800296. doi: 10.1002/jbio.201800296. Epub 2019 Jan 7.
Acetaminophen (APAP) overdose is one of the world's leading causes of drug-induced hepatotoxicity. Although traditional methods such as histological imaging and biochemical assays have been successfully applied to evaluate the extent of APAP-induced liver damage, detailed effect of how APAP overdose affect the recovery of hepatobiliary metabolism and is not completely understood. In this work, we used intravital multiphoton microscopy to image and quantify hepatobiliary metabolism of the probe 6-carboxyfluorescein diacetate in APAP-overdose mice. We analyzed hepatobiliary metabolism for up to 7 days following the overdose and found that the excretion of the probe molecule was the most rapid on Day 1 following APAP overdose and slowed down on Days 2 and 3. On Day 7, probe excretion capability has exceeded that of the normal mice, suggesting that newly regenerated hepatocytes have higher metabolic capabilities. Our approach may be further developed applied to studying drug-induced hepatotoxicity in vivo.
对乙酰氨基酚（APAP）过量是世界上导致药物性肝毒性的主要原因之一。尽管组织学成像和生化分析等传统方法已成功应用于评估 APAP 诱导的肝损伤程度，但对 APAP 过量如何影响肝胆代谢恢复的详细影响仍不完全清楚。在这项工作中，我们使用活体多光子显微镜对 APAP 过量小鼠中探针 6-羧基荧光素二乙酸酯的肝胆代谢进行成像和定量。我们分析了过量后长达 7 天的肝胆代谢，发现探针分子的排泄在 APAP 过量后的第 1 天最快，并在第 2 天和第 3 天减慢。在第 7 天，探针排泄能力已超过正常小鼠，表明新再生的肝细胞具有更高的代谢能力。我们的方法可进一步发展应用于研究体内药物性肝毒性。
