Pyridoxal phosphate and hepatocyte growth factor prevent dialysate-induced peritoneal damage.
Glucose-based peritoneal dialysate (PD) is responsible for increased accumulation of advanced glycation end products (AGE) in the peritoneum of continuous ambulatory peritoneal dialysis patients. Pyridoxal 5'-phosphate (PLP), a derivative of vitamin B(6), protects proteins from glycation. Hepatocyte growth factor (HGF) heals damaged tissues in a reciprocal manner against TGF-beta1. First, with the use of gas chromatography-mass spectrometry, whether PLP traps 3-deoxyglucosone (3DG), a major glucose degradation product in PD, was determined. Then, whether rat peritoneal tissue damages induced by intraperitoneal administration of glucose-based PD is ameliorated by PLP or HGF was examined. In vitro incubation with PLP markedly decreased concentration of 3DG in a dose-dependent manner, demonstrating the 3DG-trapping effect of PLP. The peritoneum of PD-treated rats was significantly thickened compared with that of physiologic saline-treated rats. Both PLP and HGF prevented the thickening of rat peritoneum induced by PD and ameliorated accumulation of AGE and expression of TGF-beta1, vascular endothelial growth factor, and type 1 collagen and a number of blood vessels. Furthermore, expression of HGF was significantly increased in the peritoneum of PLP-treated rats compared with that of PD-treated rats. In conclusion, PLP shows 3DG-trapping effect. PLP and HGF prevented peritoneal thickening; accumulation of AGE; expression of TGF-beta1, vascular endothelial growth factor, and type 1 collagen; and neoangiogenesis in rat peritoneum induced by PD.
Nakamura
Sakurako
S
Department of Clinical Preventive Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8560, Japan.
Niwa
Toshimitsu
T
D000818:Animals; D003847:Deoxyglucose / Q000031:analogs & derivatives* / Q000378:metabolism; D015314:Dialysis Solutions / Q000009:adverse effects; D017127:Glycation End Products, Advanced / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D008297:Male; D010531:Peritoneal Dialysis, Continuous Ambulatory / Q000009:adverse effects*; D010537:Peritoneum / Q000378:metabolism / Q000473:pathology; D010538:Peritonitis / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D011732:Pyridoxal Phosphate / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D015314:Dialysis Solutions; D017127:Glycation End Products, Advanced; D042461:Vascular Endothelial Growth Factor A; D011732:Pyridoxal Phosphate; D017228:Hepatocyte Growth Factor; D003847:Deoxyglucose; C016350:3-deoxyglucosone