Empagliflozin reduces renal calcium oxalate deposition in hyperoxaluria rats induced with ethylene glycol-ammonium chloride.

Autor: Duan Y; Guizhou Medical University, No.9 Beijing Road, Yunyan District, Guiyang, Guizhou, China; Department of Urology, Guizhou Provincial People's Hospital, No.83 East Zhongshan Road, Nanming District, Guiyang, Guizhou, China. Electronic address: danny199712@qq.com., Wang Q; Department of Urology, Guizhou Provincial People's Hospital, No.83 East Zhongshan Road, Nanming District, Guiyang, Guizhou, China. Electronic address: wangqing1@gz5055.com., Chen X; Department of Urology, Guizhou Provincial People's Hospital, No.83 East Zhongshan Road, Nanming District, Guiyang, Guizhou, China. Electronic address: atlantischan@sina.com., Deng G; Guizhou Medical University, No.9 Beijing Road, Yunyan District, Guiyang, Guizhou, China; Department of Urology, Guizhou Provincial People's Hospital, No.83 East Zhongshan Road, Nanming District, Guiyang, Guizhou, China. Electronic address: 393196351@qq.com., Huang K; Guizhou Medical University, No.9 Beijing Road, Yunyan District, Guiyang, Guizhou, China; Department of Urology, Guizhou Provincial People's Hospital, No.83 East Zhongshan Road, Nanming District, Guiyang, Guizhou, China. Electronic address: 347680693@qq.com., Sun F; Guizhou Medical University, No.9 Beijing Road, Yunyan District, Guiyang, Guizhou, China; Department of Urology, Guizhou Provincial People's Hospital, No.83 East Zhongshan Road, Nanming District, Guiyang, Guizhou, China. Electronic address: sfgmc@sina.com., Zhu J; Department of Urology, Guizhou Provincial People's Hospital, No.83 East Zhongshan Road, Nanming District, Guiyang, Guizhou, China. Electronic address: doctorzhujianguo@163.com., Jiang K; Guizhou Medical University, No.9 Beijing Road, Yunyan District, Guiyang, Guizhou, China; Department of Urology, Guizhou Provincial People's Hospital, No.83 East Zhongshan Road, Nanming District, Guiyang, Guizhou, China. Electronic address: tjjkh@sina.com.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Dec 10; Vol. 737, pp. 150912. Date of Electronic Publication: 2024 Oct 28.
DOI: 10.1016/j.bbrc.2024.150912
Abstrakt: A retrospective study reported that empagliflozin reduced the risk of urinary stone events in patients with diabetes mellitus. To further investigate empagliflozin's potential, we conducted an animal experiment to determine whether empagliflozin can prevent renal stone formation in hyperoxaluria rats. Hyperoxaluria rat models were constructed by administrating 0.75 % ethylene glycol and 1 % ammonium chloride in water. The empagliflozin-treated rats were gauged with empagliflozin at different concentrations, and their body weight and blood sugar data were recorded. After 30 days of treatment, we obtained 24-h urine, kidney, and blood samples. The urine samples were subjected to component detection. Blood samples were prepared for component detection and cytokines detection. Renal samples were subjected to von Kossa staining, transmission electron microscopy, immunohistochemistry, and transcriptome sequencing analysis. Results showed that in empagliflozin-treated hyperoxaluria rats, renal crystal deposition and mitochondria injury, urinary concentration, and excretion of oxalate were significantly decreased. Additionally, plasma levels of VEGF, IL-2, IL-1β, and MCP-1 were decreased. Immunohistochemistry showed that renal expression of KIM-1, MCP-1 was significantly decreased in empagliflozin-treated hyperoxaluria rats. Transcriptome sequencing of renal tissue represented that 25 genes were down-regulated while 12 were up-regulated in empagliflozin-treated hyperoxaluria rats. These regulated genes were mainly enriched in fatty acid metabolism, insulin resistance, muscle contraction, bile secretion, and parathyroid metabolism. Our animal experiments found that empagliflozin could reduce urinary concentration and excretion of oxalate and inhibit renal inflammation, then abating renal calcium oxalate deposition in hyperoxaluria rats in a non-diabetic state.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE