Pro-healing effects of bilirubin in open excision wound model in rats (original) (raw)

Bilirubin modulated cytokines, growth factors and angiogenesis to improve cutaneous wound healing process in diabetic rats

International immunopharmacology, 2015

Bilirubin has shown cutaneous wound healing potential in some preliminary studies. Here we hypothesize that bilirubin facilitates wound healing in diabetic rats by modulating important healing factors/candidates and antioxidant parameters in a time-dependent manner. Diabetes was induced in male Wistar rats by streptozotocin. In all diabetic rats wounds were created under pentobarbitone anesthesia. All the rats were divided into two groups, of which one (control) was treated with ointment base and other with bilirubin ointment (0.3%). Wound closer measurement and tissue collection were done on days 3, 7, 14 and 19 post-wounding. The relative expressions of hypoxia inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 alpha (SDF-1α), transforming growth factor- beta1 (TGF-β1()), tumor necrosis factor-α (TNF-α) and interlukin-10 (IL-10) mRNA and proteins and the mRNA of interlukin-1 beta (IL-1β) and matrix metalloprteinase-9 (MMP-9)...

Modulation of the Inflammatory Cytokines and Cytoprotective Enzyme by Bilirubin Treatment to Enhance Cutaneous Wound Healing in Rats

Different parts of Ficus religiosa tree have traditional usage against many ailments and diseases. In the present study, 85% ethanol extract of F. religiosa leaves were partially purified by PLC Silica gel 60 F254, 2 mm, 20X20 cm preparative thin layer chromatography using toluene and ethyl acetate (8:2, v/v) as solvent. Fraction 7 (FR7) showed highest brine shrimp larvicidal activity as regard to the leaf extract of F. religiosa. In vitro anticancer potential of same fraction against Jurkat cell line was investigated by means of flow cytometry using annexin V/7AAD apoptosis kit. F. religiosa leaf extract was found to markedly inhibit the proliferation of Jurkat cells in a dose-dependent manner.

Enhancement of incisional wound healing and neovascularization in normal rats by thrombin and synthetic thrombin receptor-activating peptides

Journal of Clinical Investigation, 1992

To better define thrombin-receptor interactions, we synthesized human thrombin peptides and identified binding-domain peptides that bind thrombin receptors and activate mitogenic signals (Glenn, K. C., G. H. Frost, J. S. Bergmann, and D. H. Carney. 1988. Pept. Res. 1:65-73). Treatment of full dermal dorsal incisions with a single topical application of thrombin receptor-activating peptide (TRAP-508) or human a-thrombin in saline enhances 7-d incisional breaking strength in normal rats up to 82% or 55% over saline-treated controls, respectively. Control wounds require 11.5 d to achieve breaking strength equivalent to TRAP-treated wounds at day 7. Thus, a single application of TRAP accelerates healing, shifting the time course forward by up to 4.5 d. Histological comparisons at day 7 show more type I collagen, less evidence of prolonged inflammation, and an increase in number and maturity of capillaries in TRAPand thrombin-treated incisions. Angiograms also show 50-65% more functional vascularization going across thrombinand TRAP-treated surgical incisions. Thus, a-thrombin and thrombin peptides, such as those released following injury, appear to initiate or enhance signals required for neovascularization and wound healing. The ability to accelerate normal wound healing events with synthetic peptides representing receptor binding domains of human thrombin may offer new options for management ofwound healing in man.

Evaluation of the effects of three natural products and a hemostatic agent on wound healing: an experimental study

Turkish Journal of Medical Sciences

Background/aim: People have used many natural materials such as plant leaves, roots, liquids derived from plants, and animal products to treat wounds throughout history. It can be said that the research on wound care in recent years have focused on traditional and natural products again. This study aimed to investigate the effects of sweetgum oil, propolis, silk protein, and Ankaferd Blood Stopper (ABS) on wound healing in an experimental excisional wound model. Materials and methods: Including 36 Balb/c inbreed mice in the study were divided equally into four groups. Two circular excisional wounds were created on the dorsal skin of mice under anesthesia using a punch biopsy device. The wounds of the first group of mice were topically dressed with sweetgum oil, the second group mice with propolis, the third group mice with silk protein, and the fourth group mice with ABS daily. Tissue samples were taken from the wounds of mice on the 7th and 14th day of wound formation, and histological examinations were performed. On the 14th day, the wounds created in all mice were healed, and the experiment was terminated. Results: Mice in the silk protein group had faster wound healing. There was no statistical difference between the groups in immunohistochemical examinations. In the ABS group, the findings of the inflammatory process were more prominent. Conclusion: In conclusions, propolis, sweetgum oil, silk protein, and ABS positively affect different parameters in wound healing and support wound healing.

Bixin Action in the Healing Process of Rats Mouth Wounds

Current Pharmaceutical Biotechnology, 2014

Oral lesions that manifest as ulcer lesions are quite common and can cause discomfort to the patient. Searching for drugs to accelerate the healing of these lesions is nonstop process. Bixin is a molecule found in annatto (urucum) seeds and is considered a viable therapeutic option to treat such lesions due to its anti-inflammatory, anti-oxidant, and healing properties. Therefore, the present study aimed to evaluate the effect of the bixin solution in the ulcer healing process in the oral mucosa of rats. Ulcers were induced with punches of 0.5 cm in the middle of the dorsum of the tongue of 64 Wistar rats. The animals were randomly divided into 8 groups, in which 4 groups were treated with saline solution, while the other 4 were treated with the bixin solution. The animals were sacrificed in the periods 2, 7, 14, and 21 days after the beginning of the treatment. The species were histologically processed and stained with hematoxylin/eosin and picrosirius. Fibroblasts, reepithelialization, and wound contraction could be observed, as could the quantification of neutrophils, macrophages, plasma cells, lymphocytes, and mature and immature collagen. On the seventh day, the experimental group, when compared to the control group, presented a higher proliferation of fibroblasts, more advanced reepithelialization, and a higher contraction in the wounds. A reduction in the average number of neutrophils in the experimental group, when compared to the control group, could be observed in all periods (p=0.000). Up to two days, the total collagen area was higher (p=0.044) in the experimental group (4139.60±3047.51than in the control group (1564.81±918.47). The deposition of mature collagen, on the 14 th day, was higher (p=0.048) in the experimental group (5802.40±3578.18) than in the control group (1737.26±1439.97). The results found in the present study indicate that the bixin solution inhibits the acute inflammatory response with a minor average number of neutrophils and accelerates reepithelialization, wound contraction and collagen maturation, thus illustrating that this solution does in fact represent an important adjuvant in the treatment of ulcers.

Systemic administration of hemoglobin improves ischemic wound healing

Journal of Surgical Research, 2014

Hemoglobin Ischemia Wound healing Oxygen a b s t r a c t Background: Oxygen plays multifaceted roles in wound healing, including effects on cell proliferation, collagen synthesis, angiogenesis, and bacterial killing. Oxygen deficit is a major factor in the pathogenesis of chronic wounds. Materials and methods: We present a novel mechanism for oxygen delivery to ischemic wounds by systemic administration of an oxygen carrier substitute derived from bovine hemoglobin (IKOR 2084) in our ischemic rabbit ear wound model. The wound healing indexes, including epithelial gap and neo-granulation tissue area, were histologically analyzed. In situ expression of endothelial cells (CD31þ) and proliferative cells (Ki-67þ) were examined by immunohistochemistry analysis. The messenger RNA expression of collagen I, III, and vascular endothelial growth factor was measured by quantitative RT-PCR. Sirius Red staining was implemented for detection of collagen deposition, and terminal deoxynucleotidyl transferase dUTP nick end labeling analysis was performed to examine dermal cellular apoptosis. Results: Systemic administration of IKOR 2084 significantly improved oxygen tension of ischemic tissue. When compared with saline controls, IKOR 2084 treatment enhanced wound repair as demonstrated by a reduced epithelial gap and increased granulation tissue area. The expression of Ki-67þ, CD31þ, vascular endothelial growth factor and collagen was also enhanced by IKOR 2084 administration. Moreover, apoptosis analysis in the wounds showed that cell survival in the dermis was increased by systemic IKOR 2084 administration. Conclusions: Our study suggests that systemic delivery of IKOR 2084 ameliorates hypoxic state, subsequently promotes angiogenesis, cellular proliferation, and collagen synthesis, attenuates hypoxia-induced apoptosis, and improved ischemic wound healing. ª

The Effect Of A Hemostatic Agent (fastact) To Wound And Tissue Repair In A Rat Model

Medical Journal of Trakya University, 2009

The purpose of this study was to test the hypothesis that the hemostatic agent (FastAct) exerts favourable effect on wound healing and tissue repair alone and along with prilocaine hydrochloride in vivo. Wound healing process is a complex procedure that starts with bleeding and hemostasis. Comprising of bovine factor proteins II, VII, IX and X, FastAct is used as a catalyst in the clot formation process to activate factors II, V, VIII and XIII.

The effect of prophylactic dose of a low molecular weight heparin on skin wound healing of rats

Acta Cirurgica Brasileira, 2009

Purpose: To investigate the effect of prophylactic dose of a low molecular weight heparin, enoxaparin, on skin wound healing of rats. Methods: Forty rats were used for the study. Rats were randomly assigned to two equal groups. Experimental group received prophylactic dose of enoxaparin. Physiologic saline was administered to the control group. Parameters of wound healing of experimental and control groups were compared. For comparison of the groups in terms of fibrosis, vascularization, inflammation, epithelization, and tensile strength test (Newton). Mann-Whitney-U test was used because variables were categorical data (fibrosis, vascularization, inflammation and epithelization). Differences between groups were analyzed with independent samples t-test (tensile strength). Significance was set at p<0.05. Results: Skin wound of the experimental group presented tensile strength significantly decreased (p<0.001), histopathologic examination revealed a significant (p<0.001) delayed epithelization and decreased in fibrosis, vascularization, inflammation (p<0.001) in the experimental group. Conclusion: Enoxaparin delay wound healing by decreased inflammatory cells, fibroblast contents and their products (growth factors), and by promoted hemorrhage.