Preservation of peritoneal morphology and function by pentoxifylline in a rat model of peritoneal dialysis: Molecular studies
Journal
Nephrology Dialysis Transplantation
Journal Volume
23
Journal Issue
12
Pages
3831-3840
Date Issued
2008
Abstract
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-β1) (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-β1 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. ? The Author [2008]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
SDGs
Other Subjects
4 (4 fluorophenyl) 2 (4 methylsulfinylphenyl) 5 (4 pyridyl)imidazole; collagen; cytokine; glucose; interleukin 6; mitogen activated protein kinase p38; monocyte chemotactic protein 1; pentoxifylline; transforming growth factor beta1; animal experiment; animal model; animal tissue; article; cell culture; cell function; cell structure; concentration response; controlled study; drug effect; drug inhibition; drug mechanism; gene expression; human; human cell; in vitro study; in vivo study; male; mesothelium cell; nonhuman; peritoneal dialysis; peritoneal fibrosis; peritoneum; priority journal; rat; Wistar rat; Animals; Base Sequence; Cells, Cultured; Collagen Type I; Cytokines; Dialysis Solutions; Disease Models, Animal; DNA Primers; Epithelial Cells; Fibrosis; Gene Expression; Glucose; Humans; Male; MAP Kinase Signaling System; p38 Mitogen-Activated Protein Kinases; Pentoxifylline; Peritoneal Dialysis; Peritoneum; Rats; Rats, Wistar; RNA, Messenger; Transforming Growth Factor beta1
Type
journal article