The Suppression of Peritoneal Advanced Glycosylation End Product Formation by Intraperitoneal Aminoguanidine

Tak, Woo Taek; Kim, Seung Ki; Lee, Jun Yeop; Kang, Hyeock Joo; Kim, Eung Suk; Lee, Jeong Ho

Abstract

BACKGOUND: The purpose of the study was to evaluate the effect of aminonguanidine on the inhibition of advanced glycosylation end product (AGE) formation and the expression of peritoneal vascular endothelial growth factor (VEGF). Then we analyzed the functional and morphological alterations of peritoneal membrane during long-term PD in rats.
METHODS
Male Sprague-Dawley rats were randomly divided into 3 groups:group I (n=6), control rats with PD catheter but not dialyzed; group II (n=9), rats dialyzed with 4.25% glucose solution for all exchanges; group III (n=9), rats dialyzed with 4.25% glucose solution containing aminoguanidine (25 mg/kg) for all changes. Dialysis changes were performed 3 times a day with 25 mL/each exchange for 12 weeks. Immunostaining was performed using a monoclonal anti-AGE antibody and a polyclonal anti-VEGF antibody. One-hour peritoneal equilibration test were performed at every 4-week for the comparison of peritoneal transport characteristics.
RESULTS
Expressions of peritoneal AGE and VEGF in dialyzed groups (group IIand III) were higher compared to control group. The level of AGE immunostaining in group III was significantly lower than in the group II. But peritoneal VEGF expression did not differ between the dialyzed groups. In dialyzed groups, D/DO glucose was significantly lower whereas D/P urea was significantly higher than in the control group. On linear regression analysis, peritoneal AGE and VEGF accumulation were directly correlated with D/DO glucose and D/P urea nitrogen. But there was no statistical significance in D/DO glucose and D/P urea nitrogen between the dialyzed groups.
CONCLUSION
Peritoneal accumulation of AGE and VEGF increased with time on CAPD in dialyzed groups. Intraperitoneal aminoguanidine was greatly suppressed peritoneal AGE accumulation but no attenuated long-term dialysis related peritoneal hyperpermeability. The VEGF formation may be one of the several mediators resulting the functional deterioration of the peritoneal membrane in long-term peritoneal dialysis.