title: Soft-tissue wound healing by anti-advanced glycation end-products agents.
abstract: The blocking of advanced glycation end-products (AGE) has been shown to reduce diabetic complications and control periodontitis. This study investigated the pattern of palatal wound-healing after graft harvesting under the administration of aminoguanidine (AG), an AGE inhibitor, or N-phenacylthiazolium bromide (PTB), a glycated cross-link breaker. Full-thickness palatal excisional wounds (5.0 x 1.5 mm(2)) were created in 72 Sprague-Dawley rats. The rats received daily intraperitoneal injections of normal saline (control), AG, or PTB and were euthanized after 4 to 28 days. The wound-healing pattern was assessed by histology, histochemistry for collagen matrix deposition, immunohistochemistry for AGE and the AGE receptor (RAGE), and the expression of RAGE, as well as inflammation- and recovery-associated genes. In the first 14 days following AG or PTB treatments, wound closure, re-epithelialization, and collagen matrix deposition were accelerated, whereas AGE deposition, RAGE-positive cells, and inflammation were reduced. RAGE and tumor necrosis factor-alpha were significantly down-regulated at day 7, and heme oxygenase-1 was persistently down-regulated until day 14. The levels of vascular endothelial growth factor, periostin, type I collagen, and fibronectin were all increased at day 14. In conclusion, anti-AGE agents appeared to facilitate palatal wound-healing by reducing AGE-associated inflammation and promoting the recovery process.
authors.affiliation: Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan.
authors.forename: P-C
authors.initials: PC
authors.lastname: Chang
authors.forename: S-C
authors.initials: SC
authors.lastname: Tsai
authors.forename: Y-H
authors.initials: YH
authors.lastname: Jheng
authors.forename: Y-F
authors.initials: YF
authors.lastname: Lin
authors.forename: C-C
authors.initials: CC
authors.lastname: Chen
mesh_terms: D000539:Alveolar Process / Q000187:drug effects / Q000473:pathology; D000818:Animals; D015815:Cell Adhesion Molecules; D002921:Cicatrix / Q000473:pathology; D003094:Collagen / Q000187:drug effects; D024042:Collagen Type I / Q000032:analysis; D015536:Down-Regulation; D005353:Fibronectins / Q000032:analysis; D017127:Glycation End Products, Advanced / Q000032:analysis / Q000037:antagonists & inhibitors*; D006146:Guanidines / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000032:analysis; D007249:Inflammation; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010159:Palate / Q000187:drug effects* / Q000601:surgery; D051381:Rats; D017207:Rats, Sprague-Dawley; D062326:Re-Epithelialization / Q000187:drug effects; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000032:analysis; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A; D058106:Wound Closure Techniques; D014945:Wound Healing / Q000187:drug effects
chemical_list: D015815:Cell Adhesion Molecules; D024042:Collagen Type I; D005353:Fibronectins; D017127:Glycation End Products, Advanced; D006146:Guanidines; C477945:N-phenacyl-4,5-dimethylthiazolium bromide; C512836:Postn protein, rat; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D003094:Collagen; D019001:Nitric Oxide Synthase; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; C004479:pimagedine
keywords: free-tissue flaps; gene expression; guanidines; thiazoles