Abstract: TH-PO0224
Disulfiram Attenuates Adenine-Induced Kidney Injury Through Modulation of Inflammatory and Metabolic Pathways
Session Information
- CKD: Mechanisms of Injury and Fibrosis - 1
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2203 CKD (Non-Dialysis): Mechanisms
Authors
- Kin, Saori, Tohoku Daigaku, Sendai, Miyagi Prefecture, Japan
- Oe, Yuji, Tohoku Daigaku, Sendai, Miyagi Prefecture, Japan
- Ishigaki, Shun, Tohoku Daigaku, Sendai, Miyagi Prefecture, Japan
- Miyazaki, Mariko, Tohoku Daigaku, Sendai, Miyagi Prefecture, Japan
- Tanaka, Tetsuhiro, Tohoku Daigaku, Sendai, Miyagi Prefecture, Japan
Background
Chronic kidney disease (CKD) is driven in part by persistent activation of innate immune pathways, leading to progressive tissue injury and fibrosis. Gasdermin D (GSDMD)-mediated pyroptosis has emerged as a key inflammatory mechanism, yet its therapeutic targeting in CKD remains unclear. Disulfiram, an approved drug for alcohol use disorder, has recently been shown to inhibit GSDMD activation. Here, we investigated whether disulfiram attenuates adenine-induced kidney injury and modulates inflammatory responses in CKD.
Methods
Adenine-induced nephropathy was established in C57BL/6J mice. Disulfiram was administered concurrently with adenine exposure. Renal function and histological injury were evaluated. Inflammatory cell infiltration and expression of inflammasome- and pyroptosis-related genes were assessed. Transcriptomic profiling was performed using RNA sequencing followed by pathway enrichment analysis.
Results
Disulfiram significantly improved renal dysfunction, as evidenced by reductions in blood urea nitrogen and plasma cystatin C levels, and reduced tubular injury score in adenine-treated mice. These changes were accompanied by marked attenuation of macrophage and neutrophil infiltration in the kidney. In parallel, expression of inflammasome- and pyroptosis-related genes including Nlrp3, Gsdmd, and Il1b, as well as pro-inflammatory cytokines, was significantly suppressed. In addition, expression of fibrosis-related genes was reduced. Transcriptomic analysis demonstrated upregulation of metabolic pathways, particularly those related to fatty acid oxidation and PPAR signaling, along with suppression of inflammation-associated pathways such as neutrophil extracellular trap formation. Finally, markers of renal senescence, including p16 and p21, as well as tubular phospho-γH2AX, were decreased following treatment.
Conclusion
Disulfiram attenuates adenine-induced kidney injury by suppressing innate immune activation and restoring metabolic pathways. Targeting immunometabolic dysregulation may represent a promising therapeutic strategy to slow CKD progression.