Inhibitory effects of caproic acid on the formation of calcium oxalate kidney stones
10.12483/j.issn.1009-8291.2026.01.012
- VernacularTitle:己酸抑制草酸钙肾结石形成的作用研究
- Author:
Yang CAO
1
;
Yuhua HUANG
1
Author Information
1. Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou 215000, China
- Publication Type:Journal Article
- Keywords:
calcium oxalate kidney stone;
short-chain fatty acid;
caproic acid;
metabolomics;
CaOx stone model
- From:
Journal of Modern Urology
2026;31(1):60-66
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of caproic acid in the formation of calcium oxalate(CaOx)kidney stones. Methods A CaOx kidney stone rat model was established using ethylene glycol and ammol/lonium chloride, and histological staining was employed to verify the model construction. Gut contents from the rats were collected, and targeted metabolomics was used to measure the levels of short-chain fatty acids(SCFAs).Sodium hexanoate solutions at 0, 0.25, 0.5, and 1.0 mmol/L, along with oxalate solutions at 0, 0.5, 1.0, and 1.5 mmol/L, were administered to human renal tubule epithelial(HK-2)cells to determine the optimal concentration of oxalate for inhibiting HK-2 cell growth. The cells were treated with these oxalate concentrations combined with varying sodium hexanoate levels for 24 hours. The cell viability was detected with CCK-8 assay, and the optimal concentration of sodium hexanoate was screened for reactive oxygen species(ROS)staining. Results After modeling, the body weight of the CaOx stone rats significantly decreased, while the kidney mass increased. TUNEL staining revealed a higher number of apoptotic cells in the kidneys of the CaOx stone rats compared to the controls. Von Kossa and Alizarin Red staining demonstrated significant calcium salt deposition, and Masson staining indicated pronounced renal fibrosis in the CaOx stone rats. Targeted metabolomics revealed four significant differential SCFAs between the controls and CaOx stone rats, with notably reduced level of caproic acid(VIP=1.367, FC=0.119)in the CaOx stone rats. CCK-8 assay showed that the optimal inhibitory concentration of oxalate in HK-2 cells was 1.0 mmol/L, sodium hexanoate of 1.0 mmol/L was the most effective to alleviate oxalate-induced renal tubular epithelial cell injury. ROS staining revealed that sodium hexanoate could reduce the ROS level in the HK-2 cells. Conclusion Caproic acid can inhibit the damage to renal tubular epithelial cells caused by CaOx and reduce the intracellular ROS level, thereby inhibiting the formation of CaOx stones. This study may provide a new direction for the treatment of CaOx stones.
