Effect of Scavenging Circulating Reactive Carbonyls by Oral Pyridoxamine in Uremic Rats on Peritoneal Dialysis

Abstract

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.

Preventive Effect of Salicylate and Pyridoxamine on Diabetic Nephropathy

“…The dosage of pyridoxamine (~200 mg/kg/day) used in this study, achieving the serum concentrations at 0.42 ± 0.29  μ M, was within a less toxic range and its preclinical efficacy has been proven in other animal models of early diabetic nephropathy, such as KK-Ay/Ta and streptozotocin-induced diabetic rats [13, 14]. The serum concentration of pyridoxamine was lower than our expectations and previous reports [30]; this may be due to its instability in aqueous solutions and photosensitivity as well as different administration methods. Using our mouse model of diabetic nephropathy, pyridoxamine treatment with 200 mg/kg/day significantly improved early to late stages of kidney injuries.…”

Premenstrual disorders: Premenstrual syndrome and premenstrual dysphoric disorder

“…Among them only pyridoxamine has an amino group and is characterized by the fact that it acts with reactive carbonyl compounds (RCOs) to eliminate their action. 94 Since RCOs act to degrade serotonin and GABA, pyridoxamine may help maintain these brain transmitters by removing the effects of RCOs. Furthermore, pyridoxamine acts to promote the synthesis of serotonin and GABA, 95 which may act to increase the concentration of these brain transmitters more effectively than pyridoxine and pyridoxal.…”

“…Vitamin B6 is consist of three forms, pyridoxine, pyridoxal, and pyridoxamine. Among them only pyridoxamine has an amino group and is characterized by the fact that it acts with reactive carbonyl compounds (RCOs) to eliminate their action 94 . Since RCOs act to degrade serotonin and GABA, pyridoxamine may help maintain these brain transmitters by removing the effects of RCOs.…”