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Updated: Sep 2, 2025
Renal Ischaemia Reperfusion Injury: A Mouse Model of Injury and Regeneration
Published on: June 7, 2014
Evaluation of nefrotoxicity by tacrolimus and micophenolate mofetil associated with kidney ischemia and reperfusion:
Alexandre Cavalheiro Cavalli1, Luis Fernando Macente Sala2, Julio Slongo3
1- Universidade Federal do Paraná, Urologia - Curitiba - PR - Brasil.
Objective:
to evaluate the renal toxicity caused by tacrolimus and mycophenolate mofetil (MMF) in a single kidney ischemia and reperfusion model.
Method:
experimental study using Wistar rats, submitted to right nephrectomy and left renal ischemia for 20 minutes, separated into groups in the postoperative period (PO): 1) Control (nonoperated); 2) Sham (operated, without PO drug); 3) TAC0.1, TAC1 and TAC10, tacrolimus administered PO at doses of 0.1mg/kg, 1mg/kg and 10mg/kg via gavage, respectively; 4) MMF, administered mycophenolate mofetil 20mg/kg; 5) MMF/TAC1 and MMF/TAC0.5, with an association of mycophenolate mofetil 20mg/kg and tacrolimus 1mg/kg and 0.5mg/kg, respectively. They were killed on the 14th PO and the kidney was removed for tissue oxidative stress analysis, by the dosage of reduced glutathione (GSH), lipoperoxidation (LPO) and protein carbonylation (PCO), and histological analysis by glomerular stereology (Glomerular volume density, Numerical density glomerular and mean glomerular volume). Renal function was evaluated by the measurement of serum creatinine and urea.
Results:
both drugs caused alterations in renal function, and the toxicity of tacrolimus was dose-dependent. Subacute toxicity did not show significant glomerular histological changes, and there was renal and compensatory glomerular hypertrophy in all groups except TAC10.
Conclusion:
Both drugs cause changes in renal function. Glomerular morphometry and stereology showed negative interference of immunosuppressants during compensatory glomerular hypertrophy.
Insights
Tacrolimus and mycophenolate mofetil (MMF) caused renal toxicity and altered kidney function in rats. Immunosuppressants negatively impacted compensatory glomerular hypertrophy, with tacrolimus toxicity being dose-dependent.
Area of Science:
- Nephrology
- Immunology
- Pharmacology
Background:
- Kidney ischemia-reperfusion injury is a significant clinical challenge.
- Immunosuppressants like tacrolimus and mycophenolate mofetil (MMF) are crucial post-transplant but can cause nephrotoxicity.
- Understanding the specific renal effects of these drugs in a compromised kidney is vital.
Purpose of the Study:
- To evaluate the renal toxicity of tacrolimus and MMF in a rat model of single kidney ischemia and reperfusion (I/R).
- To assess the impact of these immunosuppressants on renal function and glomerular structure during compensatory hypertrophy.
Main Methods:
- Wistar rats underwent right nephrectomy and left renal ischemia (20 minutes).
- Postoperative treatments included varied doses of tacrolimus, MMF, or combination therapy.
- Renal function (creatinine, urea), oxidative stress markers (GSH, LPO, PCO), and glomerular stereology were analyzed on day 14.
Main Results:
- Both tacrolimus and MMF altered renal function; tacrolimus toxicity was dose-dependent.
- No significant glomerular histological changes were observed in subacute toxicity.
- Compensatory glomerular hypertrophy occurred in most groups, except for the highest tacrolimus dose (TAC10).
Conclusions:
- Tacrolimus and MMF induce renal function changes.
- These immunosuppressants interfere with compensatory glomerular hypertrophy.
- Dose-dependent nephrotoxicity of tacrolimus was confirmed in this model.
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