Renal Matrix Metalloproteinase Activity Is Unaffected by Experimental Ischemia-Reperfusion Injury and Matrix Metalloproteinase Inhibition Does Not Alter Outcome of Renal Function

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Abstract
Background: Ischemia-reperfusion injury can lead to organ damage, such as delayed graft function in kidney transplantation. Reactive oxygen species that play a key role in this disorder may directly activate latent matrix metalloproteinases (MMP). In the kidney, little is known about the role of MMP in ischemia-reperfusion. Therefore, the aim of our study was to analyze activity/expression of MMP and to assess their functional role by the use of the MMP inhibitor BB-94 (Batimastat). Methods: Renal ischemia was induced by left renal pedicle occlusion for 60 min, preceded by right nephrectomy. Thirty-two female Sprague-Dawley rats were analyzed: sham-operated rats (n = 8), treated sham-operated rats (n = 4), ischemic rats (n = 12), and treated ischemic rats (n = 8). Batimastat therapy (30 mg/kg body weight/day) was initiated 2 days prior to induction of ischemia. Animals were sacrificed 12 h (n = 8) and 24 h (n = 24) after ischemia for analyses of MMP activity/expression and of plasma creatinine levels. Results: We found no evidence for an alteration in the activity or expression of MMP as a result of renal ischemia-reperfusion. Importantly, plasma creatinine levels significantly increased to a mean of 374 ± 61 µmol/l in ischemic rats after 24 h, almost identical to the BB-94-treated ischemic rats (384 ± 36 µmol/l). The creatinine levels in sham-operated rats remained within normal limits. Conclusion: MMP play no role during the early phase of experimental renal ischemia-reperfusion injury.