Role of peroxynitrite and recombinant human manganese superoxide dismutase in reducing ischemia-reperfusion renal tissue injury.
BACKGROUND
In an acute kidney transplant rejection rat model, we demonstrated that manganese superoxide dismutase (MnSOD) activity was significantly reduced and MnSOD was nitrated by peroxynitrite (ONOO(-)), resulting in tissue injury. We examined whether tissue injury was reduced after external supplementation of recombinant human MnSOD in a rat renal ischemia-reperfusion injury model.


METHODS
Male Brown-Norway rats underwent dissection of the right kidney. The animals were divided into 3 groups. The controls had the left renal blood vessels clamped for 90 minutes to induce ischemia, followed by reperfusion for 16 hours. In the intraperitoneal administration group, MnSOD was administered 30 minutes before ischemia and immediately before reperfusion. In the sham group, neither ischemia nor reperfusion was performed. After reperfusion, blood was collected, the left kidney was dissected and renal function and tissue injury were evaluated.


RESULTS
Serum creatinine and K(+), blood urea nitrogen, and aspartate aminotransferase activity decreased significantly, whereas serum Na(+) and renal function improved in the MnSOD group compared with the control and sham groups. On hematoxylin and eosin staining, the histological score indicated that acute tubular necrosis was significantly reduced by MnSOD administration. Periodic acid-Schiff staining was absent in the nonadministration group, whereas it persisted in the MnSOD group. In the proximal renal tubules a large proportion of anti-nitrotyrosine staining was present before but absent after MnSOD administration.


CONCLUSIONS
MnSOD administration improved renal function and reduced tissue injury. It may also reduce tissue injury in acute kidney transplant rejection and other tissue injuries caused by similar molecular mechanisms.
Rahman
N A
NA
Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.
Mori
K
K
Mizukami
M
M
Suzuki
T
T
Takahashi
N
N
Ohyama
C
C
D000818:Animals; D001806:Blood Urea Nitrogen; D003001:Cloning, Molecular; D017931:DNA Primers; D004195:Disease Models, Animal; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009392:Nephrectomy; D030421:Peroxynitrous Acid / Q000494:pharmacology* / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D011188:Potassium / Q000097:blood; D051381:Rats; D011914:Rats, Inbred BN; D011994:Recombinant Proteins / Q000627:therapeutic use; D015427:Reperfusion Injury / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000235:genetics / Q000627:therapeutic use*
D017931:DNA Primers; D011994:Recombinant Proteins; D030421:Peroxynitrous Acid; D013482:Superoxide Dismutase; D011188:Potassium