Maternal separation influences hepatic drug-metabolizing CYP450 gene expression without pathological changes in adult mice

Yazun Bashir Jarrar; Walaa’ Ashour; Abdalla Madani; Qais Jarrar; Dina Abulebdah; Yahya F. Jamous; Samah Y. Labban; Mariam Tazkarji

doi:10.1515/jbcpp-2023-0250

Article

Maternal separation influences hepatic drug-metabolizing CYP450 gene expression without pathological changes in adult mice

Yazun Bashir Jarrar , Walaa’ Ashour , Abdalla Madani , Qais Jarrar , Dina Abulebdah , Yahya F. Jamous , Samah Y. Labban and Mariam Tazkarji

Published/Copyright: March 13, 2024

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From the journal Journal of Basic and Clinical Physiology and Pharmacology Volume 35 Issue 1-2

Abstract

Objectives

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.

Methods

Eighteen Balb/c 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: cyp1a1, cyp3a11, cyp2d9, and cyp2c29.

Results

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.

Conclusions

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.

Keywords: cyp450s; drug metabolizing enzymes; gene expression; liver; maternal separation

Corresponding author: Yazun Bashir Jarrar, PhD, Department of Basic Medical Sciences, Faculty of Medicine, Al-Balqa Applied University, Al-Salt 19117, Jordan, E-mail: yazan.jarrar@bau.edu.jo

Funding source: Al-Zaytoonah University of Jordan

Funding source: University of Jordan

Award Identifier / Grant number: Unassigned

Acknowledgments

The authors would like to thank Al-Zaytoonah University of Jordan and Isra University in Jordan for supporting this research.

Research ethics: The Institution of Scientific Research Ethics at Al-Zaytoonah University in Jordan (16/4/2022-2023) approved all animal handling and use.
Informed consent: NA.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Research funding: The authors would like to extend their appreciation to Deanship of Scientific Research at Al-Zaytoonah University for funding this.
Data availability: Data are avialble with the corresponding author upon request.

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Received: 2023-12-07

Accepted: 2024-02-26

Published Online: 2024-03-13

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Articles in the same Issue

https://doi.org/10.1515/jbcpp-2023-0250

Keywords for this article

cyp450s; drug metabolizing enzymes; gene expression; liver; maternal separation