Abstract: TH-PO0119
Attenuation of Vancomycin-Associated AKI with Zileuton
Session Information
- AKI: Mechanisms - 1
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Hudson, Cole S, University of Houston College of Pharmacy, Houston, Texas, United States
- Sheikh-Hamad, David (Daud), Baylor College of Medicine Margaret M and Albert B Alkek Department of Medicine, Houston, Texas, United States
- Truong, Luan D., Houston Methodist Hospital, Houston, Texas, United States
- Tam, Vincent, University of Houston College of Pharmacy, Houston, Texas, United States
Background
Vancomycin is one of the most commonly used agents to treat antibiotic-resistant bacterial infections despite its association with acute kidney injury. Zileuton is an FDA-approved anti-inflammatory drug that we previously demonstrated could reduce aminoglycoside and polymyxin-associated acute kidney injury in an animal model. In this study, we explored if the renal protective effect of zileuton could be extended to vancomycin and sought to understand mechanism(s) of protection associated with adjuvant zileuton.
Methods
Sprague Dawley rats (n=10 per group, both genders) were administered vancomycin (200 mg/kg) daily for 10 days. Zileuton (1 and 4 mg/kg) was delivered intraperitoneally 15 minutes before antibiotic administration. Serum creatinine levels were used to evaluate acute kidney injury. Kidneys were collected and examined by light and electron microscopy. Boston University Murine Proximal Tubule (BUMPT) cells were treated with vancomycin and zileuton; cell viability, ROS levels, and p62/KEAP1 pathway-related protein levels were evaluated.
Results
Adjuvant zileuton was found to reduce acute kidney injury associated with vancomycin as evidenced by significantly reduced serum creatinine levels and histopathological abnormalities. Electron microscopy revealed that restoration of normal mitochondrial morphology was associated with nephroprotection by zileuton. In vitro, zileuton increased BUMPT cell viability, reduced ROS, and rescued HO-1 levels during vancomycin exposure.
Conclusion
Zileuton has the potential to be used as a parenteral adjuvant to attenuate vancomycin-associated acute kidney injury. The mechanism of renal protection seems to involve reducing oxidative injury to proximal tubule cells. This would allow optimal vancomycin use to treat difficult infections and make a significant impact towards combatting the antimicrobial resistance crisis.
Funding
- Other NIH Support