Metabolic profiling analysis of acute renal toxicity in mice exposed to perfluorobutanoic acid
10.20001/j.issn.2095-2619.20250802
- VernacularTitle:全氟丁酸暴露致小鼠急性肾脏毒性代谢轮廓分析
- Author:
Lin ZHONG
1
;
Yiru QIN
;
Zhiming HU
;
Zuofei XIE
;
Jingjing QIU
;
Banghua WU
;
LiHua XIA
Author Information
1. School of Public Health, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China
- Publication Type:Journal Article
- Keywords:
Perfluorobutanoic acid;
Metabolomics;
Nephrotoxicity;
Oxidative stress;
Lipid metabolism;
Metabolic pathway;
Mice
- From:
China Occupational Medicine
2025;52(4):368-375
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the nephrotoxic effects of exposure to perfluorobutanoic acid (PFBA) and its mechanism in mice, with a particular focus on analyzing the changes in kidney metabolism and their potential implications. Methods The specific pathogen free C57BL/6 mice were randomly divided into control group, low-dose group, and high-dose group, with 10 mice in each group. Mice in the three groups received intragastric administration of PFBA solution at doses of 0, 35 and 350 mg/kg body weight, once per day for seven consecutive days. The histopathological changes of kidneys of mice in these three groups were evaluated. Metabolomic profiling of mouse kidneys was performed using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Differentially accumulated metabolites (DAMs) were identified based on the Human Metabolome Database, and related metabolic pathways were analyzed through MetaboAnalyst 6.0 and Kyoto Encyclopedia of Genes and Genomes (KEGG). Results Histopathological analysis of kidneys showed that the renal pelvis mucosa of mice in the low-dose group presented focal mild inflammatory changes without marked structural damage, whereas mice in the high-dose group showed severe inflammation and partial destruction of renal structure. The kidney coefficient of mice in both low-dose group and the high-dose group decreased (both P<0.05), and the Paller scores of renal tissues increased (both P<0.05) compared with that in the control group. The Paller score of mouse renal tissue in the high-dose group was higher than that in the low-dose group (P<0.05). Metabolomic profiling identified 46 DAMs (26 upregulated, 20 downregulated) in the low-dose group and 104 DAMs (54 upregulated, 50 downregulated) in the high-dose group, with 26 shared DAMs between the two dose groups. KEGG pathway analysis revealed that DAMs were mainly involved in metabolic pathways such as glycerophospholipid metabolism, glycerolipid metabolism, sphingolipid and steroid hormone synthesis. Conclusion Acute exposure to PFBA can cause kidney injury in mice. Lipid metabolism pathways such as glycerophospholipid and sphingolipid metabolism is involved in the development of acute renal toxicity of PFBA.
