J Korean Soc Transplant.  1997 May;11(1):1-10.

Renal Ischemia/Reperfusion Injury and Cyclosporine Nephrotoxicity in the Rat Renal Isograft Model: A Pilot Study

• Jeong HJ
• Kim YS
• Yoo CH
• Kim MS
• Hong IC
• Park KI

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.

Keyword

Renal transplantation; Ischemic/reperfusion injury; Reactive oxygen species; Thioredoxin peroxidase; Cyclosporine

MeSH Terms

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
Antibodies
Cyclosporine
Peroxiredoxins
Reactive Oxygen Species
Thioredoxins