Effect of Scavenging Circulating Reactive Carbonyls by Oral Pyridoxamine in Uremic Rats on Peritoneal Dialysis.
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.
Department of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, Japan.|Unit of Translational Medicine, Department of Endocrinology and Metabolism, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Yoshitaka
Y
Mori
Department of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, Japan.|Department of Nephrology, Endocrinology and Metabolism, Tokai University Hachioji Hospital, Hachioji, Tokyo, Japan.
Takatoshi
T
Kakuta
Department of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, Japan.
Takayo
T
Miyakogawa
Division of Basic Molecular Medicine, Tokai University School of Medicine, Isehara, Japan.
Susumu
S
Takekoshi
Department of Neurology, Tokai University School of Medicine, Isehara, Japan.
Hiroko
H
Yuzawa
Department of Clinical Pharmacology, Tokai University School of Medicine, Isehara, Japan.
Hiroyuki
H
Kobayashi
Unit of Translational Medicine, Department of Endocrinology and Metabolism, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Atsushi
A
Kawakami
United Centers for Advanced Research and Translational Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
Toshio
T
Miyata
Department of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, Japan.
Masafumi
M
Fukagawa
D000284:Administration, Oral; D000818:Animals; D015314:Dialysis Solutions / Q000494:pharmacology*; D004195:Disease Models, Animal; D007676:Kidney Failure, Chronic / Q000097:blood / Q000628:therapy*; D008297:Male; D010530:Peritoneal Dialysis; D011733:Pyridoxamine / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014511:Uremia / Q000097:blood / Q000628:therapy*; D014803:Vitamin B Complex / Q000097:blood / Q000494:pharmacology*
D015314:Dialysis Solutions; D014803:Vitamin B Complex; D011733:Pyridoxamine
Carbonyl stress; Glucose degradation product; Mesothelium; Neovascularization; Pentosidine; Peritoneal dialysis; Peritoneum