TY - JOUR
T1 - Effect of Scavenging Circulating Reactive Carbonyls by Oral Pyridoxamine in Uremic Rats on Peritoneal Dialysis
AU - Mori, Yoshitaka
AU - Kakuta, Takatoshi
AU - Miyakogawa, Takayo
AU - Takekoshi, Susumu
AU - Yuzawa, Hiroko
AU - Kobayashi, Hiroyuki
AU - Kawakami, Atsushi
AU - Miyata, Toshio
AU - Fukagawa, Masafumi
PY - 2016/12/1
Y1 - 2016/12/1
N2 - Pyridoxamine, a reactive carbonyl (RCO) scavenger, can ameliorate peritoneal deterioration in uremic peritoneal dialysis (PD) rats when given via dialysate. We examined the effects of scavenging circulating RCOs by oral pyridoxamine. Rats underwent nephrectomy and 3 weeks of twice daily PD either alone or with once daily oral pyridoxamine. PD solution was supplemented with methylglyoxal, a major glucose-derived RCO, to quench intraperitoneal pyridoxamine. Oral pyridoxamine achieved comparable blood and dialysate pyridoxamine concentrations, suppressed pentosidine accumulation in the blood but not in the mesenterium or dialysate, and reduced the increases in small solute transport and mesenteric vessel densities, with no effects on submesothelial matrix layer thickening or serum creatinine. Thus, reducing circulating RCOs by giving oral pyridoxamine with PD provides limited peritoneal protection. However, orally given pyridoxamine efficiently reaches the peritoneal cavity and would eliminate intraperitoneal RCOs. Oral pyridoxamine is more clinically favorable and may be as protective as intraperitoneal administration.
AB - Pyridoxamine, a reactive carbonyl (RCO) scavenger, can ameliorate peritoneal deterioration in uremic peritoneal dialysis (PD) rats when given via dialysate. We examined the effects of scavenging circulating RCOs by oral pyridoxamine. Rats underwent nephrectomy and 3 weeks of twice daily PD either alone or with once daily oral pyridoxamine. PD solution was supplemented with methylglyoxal, a major glucose-derived RCO, to quench intraperitoneal pyridoxamine. Oral pyridoxamine achieved comparable blood and dialysate pyridoxamine concentrations, suppressed pentosidine accumulation in the blood but not in the mesenterium or dialysate, and reduced the increases in small solute transport and mesenteric vessel densities, with no effects on submesothelial matrix layer thickening or serum creatinine. Thus, reducing circulating RCOs by giving oral pyridoxamine with PD provides limited peritoneal protection. However, orally given pyridoxamine efficiently reaches the peritoneal cavity and would eliminate intraperitoneal RCOs. Oral pyridoxamine is more clinically favorable and may be as protective as intraperitoneal administration.
KW - Carbonyl stress
KW - Glucose degradation product
KW - Mesothelium
KW - Neovascularization
KW - Pentosidine
KW - Peritoneal dialysis
KW - Peritoneum
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U2 - 10.1111/1744-9987.12446
DO - 10.1111/1744-9987.12446
M3 - Article
C2 - 27620210
AN - SCOPUS:84987654731
VL - 20
SP - 645
EP - 654
JO - Therapeutic Apheresis and Dialysis
JF - Therapeutic Apheresis and Dialysis
SN - 1744-9979
IS - 6
ER -