Inhibition of intra-peritoneal carbonyl stress by carbonyl adsorbing beads or carbonyl stress inhibitor

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 17590847
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Tokai University
• Principal Investigator: KAKUTA Takatoshi Tokai University, School of Medicine, Assistant Professor, 医学部, 講師 (50276854)
• Co-Investigator(Kenkyū-buntansha): MIYATA Toshio Tokai University, School of Medicine, Professor, 医学部, 教授 (10222332)
• Project Period (FY): 2005 – 2006
• Keywords: peritoneal Dialysis / effective peritoneal surface area / advanced glycation end products / Pyridoxamine / bead / ARB / pyrazolinones-polyethyleneimine / pendisidine

Research Abstract

The molecular mechanisms underlying the peritoneal membrane (PM) failure remain elusive. Chronic uremia by itself modifies the PM and increases the effective peritoneal surface area (EPSA). PM deterioration during peritoneal Dialysis (PD) results, at least in part, from the accumulation of reactive carbonyl compounds (RCOs) present in heat-sterilized PD fluid. We have proposed two hypothetical approaches to reduce intra-peritoneal carbonyl stress. The more recently identified pyridoxamine, ARB and its analog a new class of advanced glycation end products (AGEs) inhibitors, traps RCO precursors by its amino group. Another approach to reduce intra-peritoneal carbonyl stress is the RCO adsorbing beads. Pyridoxamine, given in uremic rats with PD, significantly improved functional and structural alterations. This improvement was accompanied by reduction of AGE accumulation and of angiogenic cytokines expressions. Mixed with glucose PD fluid, pyrazolinones-polyethyleneimine, with cellulose beads (PPCB) markedly lowers RCOs (??dicarbonyls and aldehydes) and inhibits the generation of pentosidine, an AGE, to levels similar to those of filter-sterilized PD fluid. Its effectiveness is more than one order of magnitude above those of previously developed beads.

Research Products

• [Journal Article] Carbonyl stress reduction in peritoneal dialysis fluid : development of a novel high affinity adsorption bead (2007)
  • Author(s): Makoto Yamamoto
  • Journal Title: Peritoneal Inter national (In press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Carbonyl stress reduction in peritoneal dialysis fluid : development of a novel high affinity adsorption bead (2007)
  • Author(s): Makoto Yamamoto, Yuko Izuhara, Takatoshi Kakuta, Shunya Takizawa, Akio Fujita, Tatsuhiko Higaki, Charles van Ypersele de Strihou, Toshio Miyata
  • Journal Title: PD international (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Pyridoxamine improves functional, structural, and biochemical alterations of peritoneal membranes in uremic peritoneal dialysis rats (2005)
  • Author(s): Takatoshi Kakuta
  • Journal Title: Kidney International Vol.68 Pages: 1326-1336
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Pyridoxamine improves functional, structural, and biochemical alterations of peritoneal membranes in nephrectomized uremic rats on peritoneal dialysis' (2005)
  • Author(s): Takatoshi Kakuta, Reika Tanaka, Yoshinobu Satoh, Yuko Izuhara, Reiko Inagi, Masaomi Nanngaku, Akira Saito, Toshio Miyata
  • Journal Title: Kidney Int. 68 Pages: 1326-1336
  • Description: 「研究成果報告書概要(欧文)」より
• [Patent(Industrial Property Rights)] 腹膜保護剤
  • Inventor(s): 宮田敏男, 角田隆俊
  • Industrial Property Rights Holder: 学校法人東海大学
  • Industrial Property Number: 国際出願番号PCT/JP2006/310220
  • Filing Date: 国際出願日20060523
  • Description: 「研究成果報告書概要(和文)」より