Renal matrix metalloproteinase activity is unaffected by experimental ischemia-reperfusion injury and matrix metalloproteinase inhibition does not alter outcome of renal function

Background: Ischemia-reperfusion injury can lead to organ damage, such as d elayed graft function in kidney transplantation. Reactive oxygen species th at play a key role in this disorder may directly activate latent matrix met alloproteinases (MMP). In the kidney, little is known about the role of MMP in ischemia-reperfusion. Therefore, the aim of our study was to analyze ac tivity/expression of MMP and to assess their functional role by the use of the MMP inhibitor BB-94 (Batimastat). Methods: Renal ischemia was induced b y left renal pedicle occlusion for 60 min, preceded by right nephrectomy, T hirty-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 i nitiated 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/exp ression 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 isc hemia-reperfusion. Importantly, plasma creatinine levels significantly incr eased to a mean of 374 +/- 61 mu mol/l in ischemic rats after 24 h, almost identical to the BB-94-treated ischemic rats (384 +/- 36 mu mol/l). The cre atinine levels in sham-operated rats remained within normal limits. Conclus ion: MMP play no role during the early phase of experimental renal ischemia -reperfusion injury. Copyright (C) 2001 S. Karger AG, Basel.