Peritoneal fibrosis and high transport are induced in mildly pre-injured peritoneum by 3,4-dideoxyglucosone-3-ene in mice.

Abstract

Peritoneal dialysis (PD) solution contains high concentrations of glucose and glucose degradation products (GDPs). One of several GDPs--3,4-dideoxyglucosone-3-ene (3,4-DGE)--was recently identified as the most reactive and toxic GDP in PD fluids. In vitro, 3,4-DGE has been shown to induce mesothelial cell damage; however, its role in peritoneal fibrosis in vivo remains unclear. In the present study, we intraperitoneally administered chlorhexidine gluconate (CG) for mild peritoneal injury, and we then injected 3,4-DGE [38 μmol/L (low concentration) or 145 μmol/L (high concentration)] 5 times weekly for 4 weeks. Significant thickening of the parietal peritoneal membrane was observed only when treatment with low or high concentrations of 3,4-DGE occurred after CG administration, but not when either CG or 3,4-DGE alone was given. The combination of CG and 3,4-DGE also caused upregulation of messenger RNA expression of transforming growth factor β1, connective tissue growth factor, fibronectin, collagen type 1 α1 chain, alpha smooth muscle actin (α-SMA), vascular endothelial growth factor 164, NADPH oxidase 1 and 4, p22phox, p47phox, and gp91phox in peritoneal tissue. Treatment with CG alone was sufficient to cause significant F4/80-positive macrophage infiltration, appearance of α-SMA-positive cells, and vessel formation in the submesothelial layer. Addition of 3,4-DGE markedly enhanced those changes and induced apoptosis, mainly in leukocytes. The concentration of 3,4-DGE in the abdominal cavity declined more rapidly in CG-treated mice than in PBS-treated mice. Peritoneal membrane permeability determined by peritoneal equilibration test showed high transport conditions in peritoneum treated with both CG and 3,4-DGE. These results indicate that, when mild peritoneal damage is already present, 3,4-DGE causes peritoneal thickening and fibrosis, resulting in deterioration of peritoneal membrane function.

• Authors: Hideki Yokoi, Masato Kasahara, Kiyoshi Mori, Takashige Kuwabara, Naohiro Toda, Ryo Yamada, Shinji Namoto, Takashi Yamamoto, Nana Seki, Nozomi Souma, Taku Yamaguchi, Akira Sugawara, Masashi Mukoyama, Kazuwa Nakao
• Journal: Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis (Perit Dial Int) 2013 Mar-Apr Vol. 33 Issue 2 Pg. 143-54 ISSN: 1718-4304 [Electronic] United States
• PMID: 23123666 (Publication Type: Journal Article)

Chemical References

• 3,4-dideoxyglucosone-3-ene
• Actins
• Dialysis Solutions
• Pyrones
• chlorhexidine gluconate
• Chlorhexidine

Topics

• Actins (metabolism)
• Animals
• Apoptosis (drug effects)
• Chlorhexidine (analogs & derivatives)
• Dialysis Solutions (adverse effects)
• Disease Models, Animal
• Extracellular Matrix (drug effects, physiology)
• Macrophages, Peritoneal (drug effects, physiology)
• Mice
• Mice, Inbred C57BL
• Peritoneal Dialysis (adverse effects)
• Peritoneal Fibrosis (etiology, metabolism, pathology)
• Peritoneum (drug effects, metabolism, pathology)
• Pyrones (adverse effects)