Effects of AGE Inhibition with Aminoguanidine in a Diabetic <i>db/db</i> Mouse Wound Model

Abstract

Advanced glycation end products (AGEs) react non-enzymatically with tissue proteins to form irreversible structures involved in atherosclerosis, nephropathy, retinopathy, neuropathy, and wound healing. Studies on AGE-inhibitors have demonstrated possible prevention of diabetes complications. The present open label study was conducted on aminoguanidine (AGu), an inhibitor of AGE-formation, to examine potential effects on wound healing in diabetes type 2-like db/db mice during 5 - 6 weeks. The animals were divided into 4 groups: AGu from the day of wounding (day 0) topically and/or systemically in drinking water (1 g/L; group 1, n = 13); AGu 1 g/L in drinking water from 7 weeks prior to day 0 (group 2, n = 21); AGu 5 g/L in drinking water from 9 - 11 weeks prior to day 0 (group 3, n = 6); placebo controls (group 4, n = 8). Results: Glycated hemoglobin (A1C) was significantly lower in group 3 compared to the other groups ( P < 0.05). Percentage change in A1C and body weight from baseline to the end of the experiment were both related to the AGu doses (1 or 5 g/L; A1C-change, P = 0.01; weight-change, P = 0.04, both for linear trend across groups 4, 2, and 3, respectively). Even so, percentage wound closure was not improved in the AGu-treated groups compared to controls ( P ≥ 0.8).