Department of Basic Medical Sciences, Faculty of Medicine, 59303 Al-Balqa Applied University , Al-Salt, Jordan.
Department of Pharmaceutical Science, College of Pharmacy, 84977 Al-Zaytoonah University of Jordan , Amman, Jordan.
J Basic Clin Physiol Pharmacol. 2024 Mar 13;35(1-2):85-91. doi: 10.1515/jbcpp-2023-0250. eCollection 2024 Jan 1.
The principal motive of this study is to explore the influence maternal separation (MS) exhibits on the mRNA expression of major drug metabolizing-cyp450s in parallel with the assessment of pathological changes that can be induced by MS in the livers of experimental mice.
Eighteen mouse pups, comprising of both males and females, were separated from their mothers after birth. Following a six-week period during when the pups became adults, the mice were sacrificed and their livers were isolated for analysis of weight, pathohistological alterations, and the mRNA expression of drug metabolizing cyp450 genes: , , , and .
The study demonstrated that MS markedly downregulated (p<0.05) the mRNA expression of all tested drug-metabolizing cyp450s in livers of female and male mice. Furthermore, the mRNA levels of major drug-metabolizing cyp450s were notably lower (p<0.05) in livers of female MS mice as compared with male MS mice. It was found that values of the total body weight and liver weight of MS mice did not vary significantly (p>0.05) from those of the control groups. Additionally, histological examination revealed that the hepatic tissue of MS mice was normal, similar to that of the control mice.
In summary, MS downregulates the gene expression of major hepatic drug-metabolizing cyp450s without inducing pathological alterations in the livers of mice. These findings provide an explanation for the heterogeneity in pharmacokinetics and drug response of patients with early life stress.
本研究的主要目的是探讨母婴分离（MS）对实验小鼠肝脏中主要药物代谢酶 CYP450s 的 mRNA 表达的影响，并评估 MS 可能引起的肝脏病变。
将 18 只雌雄幼鼠从出生后与母亲分开。6 周后幼鼠成年，处死并分离肝脏，分析重量、组织病理学改变以及药物代谢 CYP450 基因（、、、和）的 mRNA 表达。
研究表明，MS 显著下调了雌性和雄性小鼠肝脏中所有检测到的药物代谢 CYP450s 的 mRNA 表达（p<0.05）。此外，MS 雌性小鼠肝脏中主要药物代谢 CYP450s 的 mRNA 水平明显低于 MS 雄性小鼠（p<0.05）。MS 小鼠的总体重和肝重与对照组相比无显著差异（p>0.05）。组织学检查显示 MS 小鼠的肝组织正常，与对照组相似。
总之，MS 下调了主要肝药物代谢 CYP450s 的基因表达，而不会引起小鼠肝脏的病理改变。这些发现为早期生活应激患者药代动力学和药物反应的异质性提供了解释。
