Toxicology of tramadol following chronic exposure based on metabolomics of the cerebrum in mice.

Tytuł:: Toxicology of tramadol following chronic exposure based on metabolomics of the cerebrum in mice.
Autorzy:: Xia W; School of Forensic Medicine, China Medical University, No. 77 Puhe Road, Shenbei New District, Shenyang, 110014, China.
Liu G; School of Fundamental Sciences, China Medical University, Shenyang, 110014, China.
Shao Z; School of Forensic Medicine, China Medical University, No. 77 Puhe Road, Shenbei New District, Shenyang, 110014, China.
Xu E; School of Forensic Medicine, China Medical University, No. 77 Puhe Road, Shenbei New District, Shenyang, 110014, China.
Yuan H; School of Forensic Medicine, China Medical University, No. 77 Puhe Road, Shenbei New District, Shenyang, 110014, China.
Liu J; School of Forensic Medicine, China Medical University, No. 77 Puhe Road, Shenbei New District, Shenyang, 110014, China.
Gao L; School of Forensic Medicine, China Medical University, No. 77 Puhe Road, Shenbei New District, Shenyang, 110014, China. .
Źródło:: Scientific reports [Sci Rep] 2020 Jul 07; Vol. 10 (1), pp. 11130. Date of Electronic Publication: 2020 Jul 07.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: London : Nature Publishing Group, copyright 2011-
MeSH Terms:: Analgesics, Opioid/*toxicity
Cerebrum/*drug effects
Tramadol/*toxicity
Analgesics, Opioid/administration & dosage ; Animals ; Biomarkers/analysis ; Cerebrum/chemistry ; Cerebrum/metabolism ; Male ; Malondialdehyde/analysis ; Metabolomics ; Mice ; Superoxide Dismutase/metabolism ; Tramadol/administration & dosage
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Substance Nomenclature:: 0 (Analgesics, Opioid)
0 (Biomarkers)
39J1LGJ30J (Tramadol)
4Y8F71G49Q (Malondialdehyde)
EC 1.15.1.1 (Superoxide Dismutase)
Entry Date(s):: Date Created: 20200709 Date Completed: 20201207 Latest Revision: 20210707
Update Code:: 20240105
PubMed Central ID:: PMC7341866
DOI:: 10.1038/s41598-020-67974-8
PMID:: 32636435
: Czasopismo naukowe

Pełny tekst

Tramadol is an opioid used as an analgesic for treating moderate or severe pain. The long-term use of tramadol can induce several adverse effects. The toxicological mechanism of tramadol abuse is unclear. Metabolomics is a very useful method for investigating the toxicology of drug abuse. We investigated the impact of chronic tramadol administration on the cerebrum of mice, focusing on the metabolites after tramadol administration. The mice received 20 or 50 mg/kg body weight tramadol dissolved in physiological saline daily for 5 weeks via oral gavage. Compared with the control group, the low dose tramadol group showed seven potential biomarkers, including gamma-hydroxybutyric acid, succinate semialdehyde, and methylmalonic acid, which were either up- or down-regulated. Compared with the control group, the high dose tramadol group showed ten potential biomarkers, including gamma-hydroxybutyric acid, glutamine, and O-phosphorylethanolamine, which were either up- or down-regulated. The up-regulated gamma-hydroxybutyric acid and the down-regulated succinate semialdehyde revealed that the neurotransmitter system was disrupted after tramadol abuse. Compared with the low dose tramadol group, there were twenty-nine potential biomarkers in the high dose tramadol group, mainly related to the pentose phosphate pathway and glycerophospholipid metabolism. In conclusion, metabolomics in the tramadol abuse group demonstrated that long-term tramadol abuse can result in oxidative damage, inflammation, and disruption of the GABA neurotransmitter system, which will help to elucidate the toxicology of tramadol abuse.

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