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Updated: Oct 12, 2025
Technical Refinement of a Bilateral Renal Ischemia-Reperfusion Mouse Model for Acute Kidney Injury Research
Published on: November 3, 2023
Pharmacological prevention of renal ischemia-reperfusion injury in a rat model
Yi Deng1,2, Rachel W Li1,3, Yong Liang Yang4
1Medical School, Australian National University, Canberra, Australian Capital Territory, Australia.
Introduction:
Renal ischemia-reperfusion injury (IRI) can lead to significant morbidity and mortality. It remains a leading cause of acute kidney injury and is therefore an important issue in trauma and renal transplant surgery. Various pharmaceutical agents have been used in an attempt to dampen the harmful effects of IRI but few have been shown to be useful clinically. Riluzole, Lidocaine and Lamotrigine have been demonstrated to show anti-ischaemic properties in other organs; however, their use has not been tested in the kidneys. We investigated Riluzole, Lidocaine and Lamotrigine for their preventive effects of renal IRI using a rat model.
Methods:
Winstar rats (n = 48) were divided into four groups (n = 12 per group)-three treatment groups and one control group. Riluzole, Lidocaine and Lamotrigine were given prior to renal ischemia only (IO) or IRI. The degree of ischemia was measured by glutathione levels and a TUNEL assay was used to measure DNA fragmentation.
Results:
Riluzole, Lidocaine and Lamotrigine pre-treatment each resulted in statistically higher glutathione levels compared to controls (P = 0.002; P = 0.007 and P = 0.005, respectively). Riluzole and Lidocaine were also effective at preventing depletion of glutathione following IO (P = 0.007 and P = 0.014 respectively), while Lamotrigine was ineffective in IO (P = 0.71). The degree of DNA fragmentation seen on the TUNEL assay was markedly reduced in all three-drug groups in both IO and IRI.
Discussion:
Riluzole, Lidocaine and Lamotrigine all have anti-ischaemic effects in the rat kidney and can have potential therapeutic implications.
Insights
Riluzole, Lidocaine, and Lamotrigine show promise in preventing kidney damage from ischemia-reperfusion injury (IRI). These drugs increased protective glutathione levels and reduced DNA fragmentation in a rat model, suggesting potential therapeutic benefits for renal IRI.
Area of Science:
- Nephrology
- Pharmacology
- Surgical Research
Background:
- Renal ischemia-reperfusion injury (IRI) is a significant cause of acute kidney injury, complicating trauma and transplantation.
- Current pharmaceutical interventions for IRI have limited clinical efficacy.
- Riluzole, Lidocaine, and Lamotrigine exhibit anti-ischaemic properties in other organs but their renal effects are unexplored.
Purpose of the Study:
- To investigate the potential protective effects of Riluzole, Lidocaine, and Lamotrigine against renal IRI.
- To evaluate these drugs in a preclinical rat model of kidney IRI.
Main Methods:
- Forty-eight Wistar rats were allocated into four groups: three treatment groups (Riluzole, Lidocaine, Lamotrigine) and one control group.
- Drugs were administered prior to renal ischemia only (IO) or IRI.
- Glutathione levels and DNA fragmentation (TUNEL assay) were measured to assess the degree of ischemia and cellular damage.
Main Results:
- Pre-treatment with Riluzole, Lidocaine, and Lamotrigine significantly increased renal glutathione levels compared to controls.
- Riluzole and Lidocaine effectively prevented glutathione depletion during IO, whereas Lamotrigine did not show this effect.
- All three drugs markedly reduced DNA fragmentation in both IO and IRI conditions.
Conclusions:
- Riluzole, Lidocaine, and Lamotrigine demonstrate anti-ischaemic effects in the rat kidney.
- These findings suggest potential therapeutic applications for these agents in mitigating renal IRI.
