title: Preservation of peritoneal morphology and function by pentoxifylline in a rat model of peritoneal dialysis: molecular studies.
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-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.
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China.
authors.forename: Kuan-Yu
authors.initials: KY
authors.lastname: Hung
authors.forename: Jenq-Wen
authors.initials: JW
authors.lastname: Huang
authors.forename: Chih-Kang
authors.initials: CK
authors.lastname: Chiang
authors.forename: Tun-Jun
authors.initials: TJ
authors.lastname: Tsai
mesh_terms: D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D015314:Dialysis Solutions / Q000633:toxicity; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000008:administration & dosage / Q000633:toxicity; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D010431:Pentoxifylline / Q000494:pharmacology*; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D010537:Peritoneum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D016207:Cytokines; D017931:DNA Primers; D015314:Dialysis Solutions; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose; D010431:Pentoxifylline