Evaluation of Enhanced Peritoneum Permeability in Methylglyoxal-treated Rats as a Diagnostic Method for Peritoneal Damage |
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Authors: | Shintaro Fumoto Yukiko Nakashima Koyo Nishida Yukinobu Kodama Junya Nishi Mikiro Nakashima Hitoshi Sasaki Noboru Otsuka Junzo Nakamura |
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Institution: | (1) Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan;(2) Department of Hospital Pharmacy, Nagasaki University Hospital of Medicine and Dentistry, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan;(3) Taisho Pharmaceutical Co., Ltd., 24-1 Takada 3-chome, Toshima-ku, Tokyo 170-8633, Japan |
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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. |
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Keywords: | diagnosis of peritoneal damage methylglyoxal peritoneal dialysis peritoneum permeability phenolsulfonphthalein |
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