Journal Article

Preservation of peritoneal morphology and function by pentoxifylline in a rat model of peritoneal dialysis: molecular studies

Kuan-Yu Hung, Jenq-Wen Huang, Chih-Kang Chiang and Tun-Jun Tsai

in Nephrology Dialysis Transplantation

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

Volume 23, issue 12, pages 3831-3840
Published in print December 2008 | ISSN: 0931-0509
Published online July 2008 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfn369
Preservation of peritoneal morphology and function by pentoxifylline in a rat model of peritoneal dialysis: molecular studies

Show Summary Details

Preview

Background. High-glucose (HG) content of dialysate accelerated peritoneal fibrosis. We investigated in vitro mechanisms and the in vivo potential of pentoxifylline (PTX) to prevent this fibrogenic process.

Methods. For human peritoneal mesothelial cell (HPMC) culture, a normal-glucose (NG, 5.5 mM) or HG (138 mM) medium was established through pilot experiments. The rat peritoneal dialysis (PD) model consists of four groups (n = 8): group 1, intraperitoneal (IP) HG (4.25%) solution; group 2, as group 1 plus daily IP PTX (4 mg/in 1 h); group 3, IP PTX and group 4 as control.

Results. In HPMC culture, PTX significantly prevented HG-stimulated gene and protein production of collagen and transforming growth factor-β1 (TGF-ß1) (reduction rate of 72–81%). The p38 mitogen-activated protein kinase (MAPK) pathway was activated significantly in HG-treated HPMCs. Blockade of p38 MAPK by SB203580 (25 μM) or PTX (300 μg/ml) resulted in an effective suppression of collagen and TGF-ß1 gene expression in HG-cultured HPMCs. In PD experimental animals, peritoneal thickness and collagen expression in the peritoneum were significantly increased in HG-treated rats, and was attenuated by PTX (P < 0.01). Impaired peritoneal ultrafiltration (1.9 ± 0.5 ml versus 2.4 ± 0.4 ml, P < 0.05) and stimulated proinflammatory IL-6, MCP-1 and TGF-β1 activation were observed in HG-treated rats. PTX well preserved the functional characteristics of peritoneum and cytokine profiles.

Conclusions. These in vitro and in vivo data suggest that PTX may have therapeutic benefits for the prevention or retardation of peritoneal fibrosis.

Keywords: high glucose; mesothelial cell; pentoxifylline; TGF-β1; fibrosis

Journal Article.  5680 words.  Illustrated.

Subjects: Nephrology

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.