Renal Ischemia/Reperfusion Injury and Cyclosporine Nephrotoxicity in the Rat Renal Isograft Model: A Pilot Study.
- Author:
Hyeon Joo JEONG
1
;
Yu Seun KIM
;
Chang Hyun YOO
;
Myoung Soo KIM
;
In Chul HONG
;
Ki Il PARK
Author Information
1. Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Renal transplantation;
Ischemic/reperfusion injury;
Reactive oxygen species;
Thioredoxin peroxidase;
Cyclosporine
- MeSH:
Allografts;
Animals;
Antibodies;
Clone Cells;
Cold Ischemia;
Cyclosporine*;
Delayed Graft Function;
Isografts*;
Kidney;
Kidney Transplantation;
Microscopy;
Necrosis;
Peroxiredoxins;
Pilot Projects*;
Rats*;
Reactive Oxygen Species;
Thioredoxins;
Transplants
- From:The Journal of the Korean Society for Transplantation
1997;11(1):1-10
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
Renal allografts frequently suffer from ischemia/reperfusion injury, which is a major cause of delayed graft function in renal transplantation(Tx). Cyclosporine(CsA) is known to aggravate ischemic injury, which may further heighten graft dysfunction. To know the histopathologic features of renal ischemic/reperfusion injury and cyclosporoine nephrotoxicity, we performed renal Tx between Lewis rats with cold ischemia and with/without CsA. Rats were sacrificed 3, 5, 7 days, 2, 3 and 4 weeks post-Tx. Control rats received sham operation. The kidney was processed for light microscopy and stained with H-E, PAS. Furthermore, to know the distribution of thioredoxin peroxidase(TPx), a recently cloned antioxidant in this model, the kidney tissue was stained with antibodies against three subtypes of TPx; NKEF-A /PAG(TPx A), NKEF-B/TPx(TPx B) and Mer 5. Renal isografts showed acute tubular necrosis from 3 days and recovery by 7 days, which was prolonged in CsA treated rats with signs of tubular and vascular toxicity. In sham operated rats, TPx A was distributed in all tubular segments, most prominently in distal tubules(DT). TPx B was stained in DT and collecting ducts(CD) exclusively. Mer 5 was present mainly in S3 segment. Glomerular or vascular expression was not found. In isografts TPx A expression was increased in both proximal(PT) and DT, markedly in the nonnecrotic S1 segment till 1 week postTx and returned to normal pattern by 2 weeks. TPx B and Mer 5 expression were increased till 5 days postTx with stronger staining in DT than in PT. CsA sustained the tubular expression of TPx till 4 weeks postTx. In summary, TPx expression was increased in renal tubules of rat renal isografts suffering cold ischemia, and more prolonged with CsA therapy. Marked increase of TPx A expression in S1 segment of ischemic kidneys may indicate resistance against oxidant injury, especially in S1 segment.
