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 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 micromol/l in ischemic rats after 24 h, almost identical to the BB-94-treated ischemic rats (384 +/- 36 micromol/l). The creatinine levels in sham-operated rats remained within normal limits.


CONCLUSIONS
MMP play no role during the early phase of experimental renal ischemia-reperfusion injury.
Ziswiler
R
R
Division of Nephrology and Hypertension, Inselspital Bern, Switzerland.
Daniel
C
C
Franz
E
E
Marti
H P
HP
D000818:Animals; D003404:Creatinine / Q000097:blood; D005260:Female; D005470:Fluorometry; D007150:Immunohistochemistry; D007511:Ischemia / Q000201:enzymology* / Q000503:physiopathology; D007668:Kidney / Q000201:enzymology / Q000503:physiopathology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation; D015427:Reperfusion Injury / Q000201:enzymology* / Q000503:physiopathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013876:Thiophenes / Q000494:pharmacology
D011480:Protease Inhibitors; D012333:RNA, Messenger; D013876:Thiophenes; D010649:Phenylalanine; D003404:Creatinine; C080985:batimastat; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9