title: Nesfatin-1 improves oxidative skin injury in normoglycemic or hyperglycemic rats.
abstract: Hyperglycemia is one of the major causes of suppressed angiogenesis and impaired wound healing leading to chronic wounds. Nesfatin-1 a novel peptide was reported to have antioxidant and anti-apoptotic properties. This study is aimed to investigate the potential healing-promoting effects of nesfatin-1 in non-diabetic or diabetic rats with surgical wounds. In male Sprague-Dawley rats, hyperglycemia was induced by intraperitoneal (ip) injection of streptozotocin (55 mg/kg). Under anesthesia, dorsum skin tissues of normoglycemic (n=16) and hyperglycemic rats were excised (2 × 2 cm, full-thickness), while control rats (n=16) had neither hyperglycemia nor wounds. Half of the rats in each group were treated ip with saline, while the others were treated with nesfatin-1 (2 μg/kg/day) for 3 days until they were decapitated. Plasma interleukin-1-beta (IL-1β), transforming growth factor-beta (TGF-β-1), IL-6 levels, and dermal tissue malondialdehyde (MDA), glutathione (GSH) levels, myeloperoxidase (MPO) and caspase-3 activity were measured. For histological examination, paraffin sections were stained with hematoxylin-eosin or Masson's trichrome and immunohistochemistry for vascular endothelial growth factor (VEGF) was applied. ANOVA and Student's t-tests were used for statistical analysis. Compared to control rats, skin MPO activity, MDA and caspase-3 levels were increased similarly in saline-treated normo- and hyperglycemic rats. Nesfatin-1 depressed MDA, caspase-3, MPO activity and IL-1β with concomitant elevations in dermal GSH and plasma TGF-β-1 levels. Histopathological examination revealed regeneration of epidermis, regular arrangement of collagen fibers in the dermis and a decrease in VEGF immunoreactivity in the epidermal keratinocytes of nesfatin-1-treated groups. Nesfatin-1 improved surgical wound healing in both normo- and hyperglycemic rats via the suppression of neutrophil recruitment, apoptosis and VEGF activation.
authors.affiliation: General Surgery Clinic, Bağcılar Training and Research Hospital, Istanbul, Turkey.
authors.forename: Ali
authors.initials: A
authors.lastname: Solmaz
authors.affiliation: Department of Physiology, Marmara University Faculty of Medicine, Istanbul, Turkey.
authors.forename: Elif
authors.initials: E
authors.lastname: Bahadır
authors.affiliation: General Surgery Clinic, Bağcılar Training and Research Hospital, Istanbul, Turkey.
authors.forename: Osman B
authors.initials: OB
authors.lastname: Gülçiçek
authors.affiliation: General Surgery Clinic, Bağcılar Training and Research Hospital, Istanbul, Turkey.
authors.forename: Hakan
authors.initials: H
authors.lastname: Yiğitbaş
authors.affiliation: General Surgery Clinic, Bağcılar Training and Research Hospital, Istanbul, Turkey.
authors.forename: Atilla
authors.initials: A
authors.lastname: Çelik
authors.affiliation: Department of Histology & Embryology, Marmara University Faculty of Medicine, Istanbul, Turkey.
authors.forename: Ayça
authors.initials: A
authors.lastname: Karagöz
authors.affiliation: Department of Biochemistry, Marmara University Faculty of Pharmacy, Istanbul, Turkey.
authors.forename: Derya
authors.initials: D
authors.lastname: Özsavcı
authors.affiliation: Department of Histology & Embryology, Marmara University Faculty of Medicine, Istanbul, Turkey.
authors.forename: Serap
authors.initials: S
authors.lastname: Şirvancı
authors.affiliation: Department of Physiology, Marmara University Faculty of Medicine, Istanbul, Turkey. Electronic address: byegen@marmara.edu.tr.
authors.forename: Berrak Ç
authors.initials: BÇ
authors.lastname: Yeğen
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002135:Calcium-Binding Proteins / Q000494:pharmacology*; D053148:Caspase 3 / Q000235:genetics / Q000276:immunology; D004268:DNA-Binding Proteins / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D005978:Glutathione / Q000276:immunology / Q000378:metabolism; D006943:Hyperglycemia / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D007274:Injections, Intraperitoneal; D053583:Interleukin-1beta / Q000097:blood / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D008297:Male; D008315:Malondialdehyde / Q000276:immunology / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D020556:Neutrophil Infiltration / Q000187:drug effects; D000080866:Nucleobindins; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000235:genetics / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects* / Q000276:immunology / Q000293:injuries; D013311:Streptozocin; D000072836:Surgical Wound / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000097:blood / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000276:immunology; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000975:Antioxidants; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D015850:Interleukin-6; D009419:Nerve Tissue Proteins; C000630652:Nucb1 protein, rat; D000080866:Nucleobindins; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D008315:Malondialdehyde; D013311:Streptozocin; D009195:Peroxidase; C505410:Casp3 protein, rat; D053148:Caspase 3; D005978:Glutathione
keywords: Hyperglycaemia; Nesfatin-1; Neutrophil infiltration; Oxidative injury; Surgical wound; Vascular endothelial growth factor (VEGF)