The breakdown of preformed peritoneal advanced glycation end products by intraperitoneal alagebrium.
It has been demonstrated that inhibitors of advanced glycation end products (AGE), such as aminoguanidine, can suppress peritoneal AGE in rats on peritoneal dialysis (PD). However, it is unknown whether late administration of a putative cross-link breaker, alagebrium, could reverse peritoneal AGE. We therefore compared alagebrium with aminoguanidine in their ability to reverse peritoneal AGE in rats on PD. Male Sprague-Dawley rats were randomly divided into 3 groups: group I dialyzed with 4.25% glucose solution for all exchanges; group II dialyzed with 4.25% glucose solution containing aminoguanidine, and group III dialyzed with 4.25% glucose solution containing alagebrium for last 8 weeks of 12-week dialysis period. Dialysis exchanges were performed 2 times a day for 12 weeks. Immunohistochemistry was performed using a monoclonal anti-AGE antibody. One-hour PET was performed for comparison of transport characteristics. The immunolabelling of AGE in peritoneal membrane was markedly decreased in the alagebrium group. Consistent with this, the alagebrium group exhibited significantly higher D/Do glucose and lower D/P urea, suggesting low peritoneal membrane transport. But there were no significant differences between the control and the aminoguanidine group. These results suggest that the alagebrium may be the optimal therapeutic approach, compared with treatment with inhibitors of AGE formation, in rats on PD.
Lee
Yong-Kook
YK
Department of Internal Medicine, Dongguk University Medical Center, Gyeongju, Korea.
Lee
Joon-Yeop
JY
Kim
Jun-Seup
JS
Won
Ki-Bum
KB
Kang
Hyeok-Joo
HJ
Jang
Tae-Jung
TJ
Tak
Woo-Taek
WT
Lee
Jeong-Ho
JH
D000818:Animals; D001692:Biological Transport; D001835:Body Weight; D002462:Cell Membrane / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006146:Guanidines / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D010530:Peritoneal Dialysis / Q000379:methods*; D010537:Peritoneum / Q000378:metabolism / Q000473:pathology*; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley
D017127:Glycation End Products, Advanced; D006146:Guanidines; C004479:pimagedine