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

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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.