Evaluation of enhanced peritoneum permeability in methylglyoxal-treated rats as a diagnostic method for peritoneal damage

Pharm Res. 2007 Oct;24(10):1891-6. doi: 10.1007/s11095-007-9313-5. Epub 2007 May 3.

Abstract

Purpose: As peritoneal damage in long-term peritoneal dialysis therapy is a major problem correlated to patient prognosis, diagnosis of peritoneal damage is important. To develop a diagnostic method for peritoneal damage, we focused on hyperpermeability across the peritoneum in a pathogenic peritoneal damage condition. In this study, disposition characteristics of an intraperitoneally injected marker substance in peritoneal damaged rats were analyzed.

Materials and methods: Peritoneal damaged rats were prepared by intraperitoneal injection of a glucose degradation product, methylglyoxal (MGO), for five or ten consecutive days. Phenolsulfonphthalein (PSP), as a marker substance, was intraperitoneally or intravenously injected into MGO-treated rats. Subsequently, the PSP disposition characteristics were pharmacokinetically analyzed.

Results: In both cases of 5 and 10 days treatment of MGO, absorption of PSP after intraperitoneal injection was significantly enhanced. Plasma concentration and urinary excretion of PSP in MGO-treated rats were also higher than those in saline-treated rats in the early phase. On the contrary, there was no significant difference in terms of the pharmacokinetic parameters of intravenously injected PSP in saline- or MGO-treated rats. These results indicated that intraperitoneally injected MGO primarily acts on the peritoneal membrane; therefore, the peritoneal permeability of the marker substance was enhanced.

Conclusion: We demonstrated that pharmacokinetic analysis of peritoneum permeability might be a potent diagnostic method for peritoneal damage in experimental animals and patients receiving peritoneal dialysis.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Indicators and Reagents / administration & dosage
  • Indicators and Reagents / pharmacokinetics*
  • Injections, Intraperitoneal
  • Injections, Intravenous
  • Male
  • Peritoneal Diseases / chemically induced
  • Peritoneal Diseases / diagnosis*
  • Peritoneal Diseases / metabolism*
  • Permeability
  • Phenolsulfonphthalein / administration & dosage
  • Phenolsulfonphthalein / pharmacokinetics*
  • Pyruvaldehyde
  • Rats
  • Rats, Wistar
  • Tissue Distribution

Substances

  • Indicators and Reagents
  • Pyruvaldehyde
  • Phenolsulfonphthalein