Abstract: FR-PO1081
Uremic Toxin Indoxyl Sulfate Impairs Hydrogen Sulfide Formation in Nephrectomy Rats
Session Information
- CKD Mechanisms: Progression, Fibrosis, and Beyond
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Author
- Lu, Chien-Lin, Fu Jen Catholic University, New Taipei, Taiwan
Background
Hydrogen sulfide (H2S) has antioxidant properties but is reduced in CKD, making the cells more vulnerable to oxidative damage. The interaction between Indoxyl Sulfate (IS) and H2S in CKD needs further exploration.
Methods
Male Wistar rats had nephrectomy and received CH-223191, an AhR antagonist. Blood and urine samples were collected post-treatment for H2S level measurement. Kidney tissue was evaluated for H2S-producing enzyme and Sp1 protein activity, and reduced GSH and oxidized GSSG levels.
Results
Administering CH-223191 to rats after nephrectomy prevented the harmful effects of IS on the kidneys. CH-223191 restored H2S levels, reduced IS accumulation, and reversed the changes in H2S-producing enzymes and the transcription factor Sp1 (Fig1). It also decreased oxidative stress and lipid peroxidation in the nephrectomy rats(Fig2). These findings indicate that CH-223191 protects against kidney damage by mitigating IS-induced effects, preserving H2S generation, and reducing oxidative stress.
Conclusion
Impaired H2S generation caused by IS renders the kidney susceptible to oxidative stress damage, representing one of the mechanisms underlying IS-mediated kidney function loss.