Preservation of Peritoneal Morphology and Function by Pentoxifylline in a Rat Model of Peritoneal Dialysis Molecular Studies

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-beta1 ( 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 microM) or PTX (300 microg/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-beta1 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