Abstract: SA-PO0175
Effect of Diazepam on Ischemia-Reperfusion Injury (IRI) in Rats in Relation to the Dose and Timing of Administration
Session Information
- AKI: Mechanisms - 3
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Wystrychowski, Grzegorz, Wojewódzki Szpital Specjalistyczny nr 4, Bytom, Silesian Voivodeship, Poland
- Wichary, Piotr, Slaski Uniwersytet Medyczny w Katowicach, Katowice, Silesian Voivodeship, Poland
- Wystrychowski, Wojciech, Slaski Uniwersytet Medyczny w Katowicach, Katowice, Silesian Voivodeship, Poland
- Wystrychowski, Antoni, Slaski Uniwersytet Medyczny w Katowicach, Katowice, Silesian Voivodeship, Poland
Background
We have previously found that diazepam pretreatment can reduce renal IRI in rats. Hereby, we assessed if this effect depends on the dose or timing of administration.
Methods
14 days after unilateral nephrectomy, male S-D rats underwent a 45' kidney ischemia. In experiment 1, 60' before ischemia rats were injected sc with 0.75mg (n=18) or 0.25mg diazepam (n=19) or 0.5mL 0.9% NaCl (n=18). In experiment 2 0.75mg diazepam was given 60' before ischemia (n=8), at ischemia onset (n=8), at reperfusion onset (n=9), 60' into reperfusion (n=10), or 0.5mL 0.9% NaCl was given each time (n=10).
Results
In experiment 1, 48h after IRI only in rats given 0.75mg diazepam was serum creatinine (SCreat) lower, creatinine clearance (CreatCl) higher, and urinary Na and K losses lesser than in controls. Also, CreatCl was higher than with 0.25mg diazepam (fig.1). At 7 days both diazepam groups had Screat lower by 25-30% vs. controls, but only with the higher dose was proteinuria reduced by 51%.
In experiment 2, at 48h SCreat rise was lower by 45-55% in all diazepam groups, however CreatCl was improved only with injection at 60' prior to IRI (fig.2). At 7 days SCreat remained lower by 33-42% in diazepam groups. Yet, only with administration at 60' prior to IRI was proteinuria lower by 53% and serum K higher by 0.62 mmol/L vs. controls.
Conclusion
Diazepam pretreatment attenuates AKI due to IRI in a dose-dependent manner. Diazepam is nephroprotective to a slightly lesser degree also when given at ischemia onset, at or shortly into reperfusion. The potential applicability of diazepam spans from anticipated up to established renal IRI.
Funding
- Government Support – Non-U.S.