Department of Legal Medicine, Graduate School of Medicine, Osaka Metropolitan University, Abeno, Osaka, Japan.
Forensic Autopsy Section, Medico-legal Consultation and Postmortem Investigation Support Center, C/O Department of Legal Medicine, Graduate School of Medicine, Osaka Metropolitan University, Abeno, Osaka, Japan.
Hum Exp Toxicol. 2023 Jan-Dec;42:9603271231171643. doi: 10.1177/09603271231171643.
The present study aimed to clarify the expressions and roles of clock genes involved in drug metabolism in patients taking benzodiazepines (BZDs), as well as the drug metabolism regulators controlled by clock genes for each BZD type. The relationships between the expressions of the clock genes , , and and the drug-metabolizing enzymes and were investigated using livers from BZD-detected autopsy cases. In addition, the effect of BZD exposure on various genes was examined in HepG2 human hepatocellular carcinoma cells. The expressions of , and in the liver were lower in the diazepam-detected group than in the non-detected group. Furthermore, expression correlated with expression. Cell culture experiments showed that the expressions of and decreased, whereas those of and increased after diazepam and midazolam exposure. The results of the analyses of autopsy samples and cultured cells suggested that regulates when exposed to BZD. Understanding the relationship between these clock genes and CYPs may help achieve individualized drug therapy.
本研究旨在阐明参与苯二氮䓬类药物（BZDs）代谢的时钟基因的表达和作用，以及每种 BZD 类型受时钟基因控制的药物代谢调节剂。使用从 BZD 检测到的尸检病例的肝脏研究了时钟基因 、 和 的表达与药物代谢酶 和 之间的关系。此外，还在 HepG2 人肝癌细胞中检查了 BZD 暴露对各种基因的影响。与非检测组相比，在检测到地西泮的组中，肝脏中的 、 和 的表达水平较低。此外， 的表达与 的表达相关。细胞培养实验表明，地西泮和咪达唑仑暴露后， 和 的表达降低，而 和 的表达增加。尸检样本和培养细胞的分析结果表明， 调节 暴露于 BZD 时的表达。了解这些时钟基因和 CYP 之间的关系可能有助于实现个体化药物治疗。
