title: Collagen ultrastructure and TGF-beta1 expression preserved with aminoguanidine during wound healing in diabetic rats.
abstract: Advanced glycoxidation end products have been implicated in delayed diabetic wound healing. In this study, we evaluated the effects of aminoguanidine, which is an advanced glycation and nitric oxide (NO) synthase inhibitor, on extracellular matrix protein expression, collagen configuration, and nitrite/nitrate levels in wounds of diabetic rats. Sixteen Wistar male rats were made diabetic by streptozotocin. Of these, eight rats were given AG (aminoguanidine bicarbonate (AG) (group DAG) in their drinking water, and eight rats were followed as diabetic paired controls (group D). Eight healthy rats were followed as the healthy control group (group H). At the eighth week, a 2 x 2 cm area full-thickness skin defect was created. The degree of contraction of the open wounds was evaluated for 2 weeks duration. On the 15th postoperative day, wound surface areas were measured, and wound specimens and blood samples were collected. The shrinking percentage of the wounds was small in both groups H and DAG compared with group D (p < 0.05). Similar to healthy rats, the aminoguanidine-treated diabetic rats had very strong transforming growth factor (TGF)-beta1 expression in granulation tissue and intact skin in comparison with diabetic controls. In the diabetic group, the intact skin demonstrated sparsely distributed regular collagen fibers in the granulation zone, and the regular pattern of collagen fibers was lost. In conclusion, aminoguanidine improves wound healing, restores growth factor TGF-beta1 expression, and preserves collagen ultra structure, whereas it has no prominent effect on NO levels within wound tissue in diabetic rats.
authors.affiliation: Marmara University Medical School, Section of Endocrinology and Metabolism, Istanbul, Turkey. dilekyavuz2004@yahoo.com
authors.forename: Dilek
authors.initials: D
authors.lastname: Yavuz
authors.forename: Halil
authors.initials: H
authors.lastname: Tuğtepe
authors.forename: Sule
authors.initials: S
authors.lastname: Cetinel
authors.forename: Suheyla
authors.initials: S
authors.lastname: Uyar
authors.forename: Handan
authors.initials: H
authors.lastname: Kaya
authors.forename: Goncagül
authors.initials: G
authors.lastname: Haklar
authors.forename: Sabahat
authors.initials: S
authors.lastname: Civelek
authors.forename: Oguzhan
authors.initials: O
authors.lastname: Deyneli
authors.forename: Tangül
authors.initials: T
authors.lastname: San
authors.forename: Gülden
authors.initials: G
authors.lastname: Burçak
authors.forename: Sema
authors.initials: S
authors.lastname: Akalin
mesh_terms: D000818:Animals; D003094:Collagen / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical; D004848:Epithelium / Q000737:chemistry / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000648:ultrastructure; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology*; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008854:Microscopy, Electron; D009566:Nitrates / Q000097:blood / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood; D009573:Nitrites / Q000097:blood / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000293:injuries / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D014945:Wound Healing / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D014947:Wounds and Injuries / Q000378:metabolism / Q000473:pathology
chemical_list: D016326:Extracellular Matrix Proteins; D017127:Glycation End Products, Advanced; D006146:Guanidines; D009566:Nitrates; D009573:Nitrites; C508962:Tgfb1 protein, rat; D017392:Thiobarbituric Acid Reactive Substances; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D009569:Nitric Oxide; D003094:Collagen; C004479:pimagedine