Journal Article

Addition of oleic acid to delipidated bovine serum albumin aggravates renal damage in experimental protein-overload nephrosis

Mirjan M. van Timmeren, Stephan J. L. Bakker, Coen A. Stegeman, Rijk O. B. Gans and Harry van Goor

in Nephrology Dialysis Transplantation

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

Volume 20, issue 11, pages 2349-2357
Published in print November 2005 | ISSN: 0931-0509
Published online September 2005 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfh964
Addition of oleic acid to delipidated bovine serum albumin aggravates renal damage in experimental protein-overload nephrosis

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Background. Non-esterified fatty acids (NEFA) carried on albumin may have a causal role in the development of chronic proteinuria-induced nephropathy. To investigate whether NEFA aggravate renal structural damage, we studied the effects of NEFA addition to delipidated bovine serum albumin (BSA) in protein-overload nephropathy.

Methods. Three groups of Wistar rats received daily intraperitoneal injections (3 weeks) of either 1 g NEFA-free BSA (BSA-0), or NEFA-free BSA with three (BSA-3) or six (BSA-6) molecules oleic acid added per BSA molecule. An additional group received saline injections only (SAL). Renal damage was evaluated by immunohistochemistry and RT–PCR.

Results. Interstitial and glomerular alpha-smooth muscle actin (α-SMA, marker of myofibroblast transformation) expression were higher in BSA-3/6 than in saline-injected controls (P<0.001). Glomerular macrophage influx and desmin (marker of glomerular epithelial cell damage) expression were higher in all BSA-injected rats than SAL (P<0.001). Interstitial macrophage influx was elevated in BSA-0/3 (P<0.05) and BSA-6 (P<0.001) compared to SAL. Addition of six molecules of oleic acid to BSA revealed higher interstitial and glomerular α-SMA expression (P<0.001), increased interstitial macrophage numbers (P<0.001) and enhanced glomerular desmin expression (P<0.05) compared to BSA-0. RT–PCR revealed higher glomerular α-SMA mRNA expression in BSA-3/6 than SAL (P<0.001 and 0.05, respectively), interstitial α-SMA mRNA was elevated in BSA-6 (P<0.05). Interstitial TGF-β1 mRNA expression was significantly higher in BSA-3 than SAL (P<0.05).

Conclusions. These data show that addition of oleic acid to NEFA-free BSA aggravates renal damage, suggesting a role for NEFA in the pathogenesis of proteinuric nephropathies.

Keywords: albuminuria; non-esterified fatty acids; oleic acid; protein-overload; proteinuric nephropathies

Journal Article.  4135 words.  Illustrated.

Subjects: Nephrology

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