Mechanistic study of combined poisoning of diazepam and ethanol based on metabolomics
10.13618/j.issn.1001-5728.2025.03.004
- VernacularTitle:基于代谢组学的地西泮和乙醇联合中毒机制研究
- Author:
Ni HU
1
;
Lishuang LIU
;
Yiwei GUO
;
Tao WANG
;
Zhimei BAI
;
Jing ZHANG
;
Jiajie ZHANG
;
Bochao LI
;
Pingrong ZHOU
;
Hongwei LIU
;
Zhiwen WEI
;
Keming YUN
;
Lele WANG
Author Information
1. 山西医科大学,山西晋中 030600;法医学山西省重点实验室,山西晋中 030600;法庭毒物分析公安部重点实验室,山西晋中 030600
- Publication Type:Journal Article
- Keywords:
Combined poisoning;
Metobolomics;
Diazepam;
Ethanol
- From:
Chinese Journal of Forensic Medicine
2025;40(3):284-287
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the plasma metabolomics of mice poisoned by different dosage of the combination of diazepam and ethanol,and to reveal the toxicological mechanisms of combined poisoning of diazepam and ethanol.Methods Female Kunming mice were randomly divided into blank group,single and combined poisoning group(n=6),Based on the LD50 of diazepam co-administered with graded ethanol doses,mice in the single-drug and combined groups received oral gavage at 1/2,1,and 2 × LD50.Retro-orbital blood samples(~500 μL)were collected within 24 hours post-administration and analyzed by UPLC-QE-MS technology.Principal component analysis and orthogonal partial least squares discriminant analysis were used to identify differential metabolites and associated metabolic pathways.Results A total of 387 differential metabolites were identified in the combined poisoning group of diazepam and ethanol implicating the key pathways including tryptophan metabolism,phenylalanine metabolism,arginine and proline metabolism,Glycerophospholipid metabolism,phenylalanine,tyrosine and tryptophan biosynthesis.Conclusion Combined diazepam and ethanol poisoning exerts significant systemic effects by disrupting neurotransmitters conduction,exacerbating oxidative stress response and dysregulating energy metabolism.