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Evaluation of Enhanced Peritoneum Permeability in Methylglyoxal-treated Rats as a Diagnostic Method for Peritoneal Damage
Authors:Shintaro Fumoto  Yukiko Nakashima  Koyo Nishida  Yukinobu Kodama  Junya Nishi  Mikiro Nakashima  Hitoshi Sasaki  Noboru Otsuka  Junzo Nakamura
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
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.
Keywords:diagnosis of peritoneal damage  methylglyoxal  peritoneal dialysis  peritoneum permeability  phenolsulfonphthalein
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