Metabolic abnormalities associated with ketamine-associated bladder toxicity based on metabolomics
10.16438/j.0513-4870.2020-0017
- VernacularTitle:基于代谢组学探索氯胺酮膀胱毒性相关的尿液差异代谢物
- Author:
Zhi-gui WU
1
;
Wen-xian YIN
2
;
Hong-li LUO
1
;
Yuan-kai SI
1
;
Meng-qi SUN
1
;
Lin-chuan LIAO
3
Author Information
1. Department of Pharmacy, Affiliated Hospital of Southwest Medical University, Luzhou 646000, China
2. Department of Pharmacy, Hospital of Traditional Chinese Medicine Affiliated to Southwest Medical University, Luzhou 646000, China
3. West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu 610041, China
- Publication Type:Research Article
- Keywords:
etamine;
metabolomics;
bladder toxicity;
3-aminoisobutyric acid;
citric acid;
uric acid
- From:
Acta Pharmaceutica Sinica
2020;55(8):1849-1854
- CountryChina
- Language:Chinese
-
Abstract:
The aim of the present study was to determine the metabolic changes and possible toxic mechanisms of ketamine-associated bladder toxicity. Twenty-four male Sprague-Dawley (SD) rats were randomly allocated into a control group, a low-dose group and a high-dose group. The behavior of these rats was observed every day. In addition, the weight, 2 h urinary frequency and organ coefficient of the bladder were measured. Serum IL-6 and TNF-α levels were measured using an enzyme-linked immunosorbent assay (ELISA). Urinary metabolites were analyzed using gas chromatography-mass spectrometry (GC-MS). This research was approved by the Ethics Committee of the Animal Experiment Center of Southwest Medical University (No. 201901-98). After 12 weeks of administration, the frequency of 2 h urination and the bladder mass index were significantly different in the low-dose and high-dose groups compared with the control group. Serum IL-6 and TNF-α levels were higher than those of the control group (P<0.05). Bladder HE staining showed that long-term administration of ketamine could induce cystitis. The concentrations of the three common differential metabolites, including 3-aminoisobutyric acid, citric acid and uric acid in the low-dose and the high-dose groups were increased compared with those in the control group. This study indicates that 3-aminoisobutyric acid, citric acid and uric acid and their related metabolic pathways may be closely related to ketamine-associated bladder toxicity.
