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Updated: Jul 10, 2026
Renal Ischaemia Reperfusion Injury: A Mouse Model of Injury and Regeneration
Published on: June 7, 2014
[Effects of mycophenolate mofetil in ischemic acute renal failure in rats]
M Chávez-Velásquez1, H Pons, M Medina
1Centro de Medicina y Cirugía Experimental, Facultad de Medicina, Universidad del Zulia, Unidad de Diálisis y Trasplante Renal Hospital Universitario de Maracaibo, Venezuela. Mard18@hotmail.com
Abstract:
Mycophenolate mofetil (MMF) is a purine synthesis inhibitor commonly used as immunosupresive agent in transplantation. Kidney grafts undergo more or less prolonged cold ischemia after harvesting which results in variable degrees of ischemia reperfusion injury. To determine whether the inhibition of early events of cellular infiltration may influence the severity of damage induced by ischemic acute renal failure, 45 Sprague Dawley rats were given MMF at a dose of 20mg/kg/day (MMF-rats) by gavage 2 days before (pre-MMF group, n=15) or after (post-MMF group, n=15) clamping the left renal artery for 40 minutes followed by rigt-sided nephrectomy. (control group, n=15) received vehicle. Serum Creatinine (Screat) was measured daily in all groups. On the 2nd post-ischemic day Screat was significantly lower (p=0.001) in pre-MMF group compared with post-MMF group and control group (4 +/- 2mg/dl post-MMF group vs 1.7 +/- 1.2 mg/dl pre-MMF group, control group 5+/-2, p< 0.05). Kidney biopsies shown that the histologic damage was 54 +/- 28% in post-MMF group vs 34+/- 22% in pre-MMF group and 61 +/- 25% in control group (pre-MMF vs post-MMF, p NS). On the 5th day post-ischemic, MMF-rats showed more severe tubulointerstitial necrosis (pre-MMF group: 17 +/- 20 %, post-MMF group: 33 +/- 27%) than controls (4 +/- 5%). The severity of ATN was significantly higher in post-MMF group compared with controls (p=0.01). Tubulointersticial T-lymphocyte (T CD 5) and monocyte (ED 1) infiltration evaluated on the 2nd post-ischemic day was less intense in group I (T CD5: 3 +/- 3, ED 1: 10 +/- 9, cel/mm2) compared to post-MMF group (T CD 5: 10 +/- 4, ED 1: 55 +/- 40) and to control group (T CD 5: 10+/- 4, ED 1: 64 +/- 46). However, on the 5th post-ischemia day, ED 1 infiltration was significantly higher in post-MMF group (24 +/- 18%) compared to pre-MMF group (5 +/- 5, p NS) and also in pre-MMF group vs control group (31 +/- 33, p< 0.05). Our results suggest that MMF given before a renal ischemic insult may reduce the severity of histologic damage resulting from ischemia reperfusion injury.
Insights
Mycophenolate mofetil (MMF) administered before renal ischemia reduced kidney damage and cellular infiltration. Pre-treatment with MMF improved outcomes compared to post-treatment or no treatment, suggesting a protective effect against ischemia reperfusion injury.
Area of Science:
- Nephrology
- Immunology
- Transplantation
Background:
- Kidney grafts are susceptible to ischemia reperfusion injury (IRI) due to cold ischemia.
- Early cellular infiltration contributes to IRI severity.
- Mycophenolate mofetil (MMF) is an immunosuppressant that inhibits purine synthesis.
Purpose of the Study:
- To investigate the effect of MMF timing on IRI in a rat model.
- To determine if inhibiting early cellular infiltration impacts IRI severity.
Main Methods:
- 45 rats underwent renal artery clamping and contralateral nephrectomy.
- MMF was administered either 2 days before (pre-MMF) or after (post-MMF) ischemia, or vehicle (control).
- Serum creatinine, kidney histology, and cellular infiltration (T-lymphocytes, monocytes) were assessed.
Main Results:
- Pre-MMF group showed significantly lower serum creatinine on post-ischemic day 2 compared to post-MMF and control groups.
- Histologic damage was lower in the pre-MMF group than the post-MMF group on day 2.
- While MMF reduced T-lymphocyte and monocyte infiltration on day 2, tubulointerstitial necrosis was more severe in MMF-treated groups by day 5.
Conclusions:
- Pre-treatment with MMF may mitigate histologic damage from renal IRI.
- The timing of MMF administration is critical in managing IRI.
- Further research is needed to understand the long-term effects and mechanisms of MMF in IRI.
