Journal Article

Pargyline reduces renal damage associated with ischaemia–reperfusion and cyclosporin

Rana Chaaya, Chiara Alfarano, Céline Guilbeau-Frugier, Christelle Coatrieux, Anne-Sylvie Kesteman, Angelo Parini, Nassim Fares, Michelle Gue, Joost P. Schanstra and Jean-Loup Bascands

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 26, issue 2, pages 489-498
Published in print February 2011 | ISSN: 0931-0509
Published online July 2010 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfq445
Pargyline reduces renal damage associated with ischaemia–reperfusion and cyclosporin

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Background. The slow deterioration of the kidney graft is characterized histologically by interstitial fibrosis and tubular atrophy (IFTA). Immunological and non-immunological stress is the main cause of progression towards IFTA. Our study focused on the non-immunological injuries induced by ischaemia–reperfusion (IR) and cyclosporin (CsA) toxicity, which remain the two stress factors putting a damper on the outcome of the renal graft. Endogenous reactive oxygen species (ROS) are essentially produced by mitochondria, and we have previously shown that the blockage of the mitochondrial enzymes monoamine oxidases (MAOs) prevents H2O2 production in the early reperfusion stage following IR.

Methods. We used a rat model of IFTA consisting in unilateral nephrectomy followed by IR and daily CsA administration. Four weeks after IR, we analysed renal function, histological alterations and a number of inflammatory and fibrotic genes.

Results. We observed, 28 days after pargyline-mediated blockade of MAO (before or after IR), improved renal function as well as a net decrease in renal inflammation associated to lower IL-1β and TNF-α gene expression. However, significant reduction in apoptosis, necrosis and fibrosis was only observed when pargyline was administrated before IR. This protective effect was associated to decreased expression of TGF-β1, collagen types I, III and IV and also to the normalization of antioxidant (SOD1, catalase) and inflammatory (COX2, LOX5) gene expression.

Conclusion. It appears that the blockage of ROS produced by MAO and subsequent cell death might be an effective protective strategy against IFTA progression.

Keywords: IFTA; ischaemia–reperfusion; MAO; oxidative stress

Journal Article.  5501 words.  Illustrated.

Subjects: Nephrology

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