Adverse effects of dietary glycotoxins on wound healing in genetically diabetic mice.
Advanced glycoxidation end products (AGEs) are implicated in delayed diabetic wound healing. To test the role of diet-derived AGE on the rate of wound healing, we placed female db/db (+/+) (n = 55, 12 weeks old) and age-matched control db/db (+/-) mice (n = 45) on two diets that differed only in AGE content (high [H-AGE] versus low [L-AGE] ratio, 5:1) for 3 months. Full-thickness skin wounds (1 cm) were examined histologically and for wound closure. Serum 24-h urine and skin samples were monitored for N(epsilon)-carboxymethyl-lysine and methylglyoxal derivatives by enzyme-linked immunosorbent assays. L-AGE-fed mice displayed more rapid wound closure at days 7 and 14 (P < 0.005) and were closed completely by day 21 compared with H-AGE nonhealed wounds. Serum AGE levels increased by 53% in H-AGE mice and decreased by 7.8% in L-AGE mice (P < 0.04) from baseline. L-AGE mice wounds exhibited lower skin AGE deposits, increased epithelialization, angiogenesis, inflammation, granulation tissue deposition, and enhanced collagen organization up to day 21, compared with H-AGE mice. Reepithelialization was the dominant mode of wound closure in H-AGE mice compared with wound contraction that prevailed in L-AGE mice. Thus, increased diet-derived AGE intake may be a significant retardant of wound closure in diabetic mice; dietary AGE restriction may improve impaired diabetic wound healing.
Division of Experimental Diabetes and Aging, Department of Geriatrics, Mount Sinai School of Medicine, New York, New York 10029, USA.
Melpomeni
M
Peppa
Harold
H
Brem
Paul
P
Ehrlich
Jian-Gang
JG
Zhang
Weijing
W
Cai
Zhu
Z
Li
Anca
A
Croitoru
Swan
S
Thung
Helen
H
Vlassara
D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000235:genetics* / Q000503:physiopathology*; D004032:Diet; D017127:Glycation End Products, Advanced / Q000008:administration & dosage / Q000378:metabolism* / Q000633:toxicity*; D051379:Mice; D008817:Mice, Mutant Strains; D012867:Skin / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D014945:Wound Healing / Q000187:drug effects*
D001786:Blood Glucose; D017127:Glycation End Products, Advanced