scholarly journals Redox treatment ameliorates diabetes mellitus-induced skin flap necrosis via inhibiting apoptosis and promoting neoangiogenesis

2020 ◽  
pp. 153537022097426
Author(s):  
Yeon S Kim ◽  
Hye-Young Lee ◽  
Jeon Y Jang ◽  
Hye R Lee ◽  
Yoo S Shin ◽  
...  

Intractable wound healing is the habitual problem of diabetes mellitus. High blood glucose limits wound healing by interrupting inflammatory responses and inhibiting neoangiogenesis. Oxidative stress is commonly thought to be a major pathogenic cause of diabetic complications. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one, EDV) is a free radical scavenger which suppress oxidative stress. This study investigates whether EDV can reduce oxidative stress in wound healing HaCaT/human dermal fibroblasts cells (HDFs) in vitro and in vivo animal model. Cell viability and wound healing assays, FACS flow cytometry, and Hoechst 33342 staining were performed to confirm apoptosis and cytotoxicity in H2O2 and EDV-treated HaCaT and HDFs. A streptozotocin-induced hyperglycemic animal model was made in adult C57BL6 mice. Full-thickness skin flap was made on dorsomedial back and re-sutured to evaluate the wound healing process. EDV was delivered slowly in the skin flap with degradable fibrin glue. The flap was monitored and analyzed on postoperative days 1, 3, and 5. CD31/DAPI staining was done to detect newly formed blood vessels. The expression levels of NF-κB, bcl-2, NOX3, and STAT3 proteins in C57BL6 mouse tissues were also examined. The wound healing process in hyper- and normoglycemic mice showed a difference in protein expression, especially in oxidative stress management and angiogenesis. Exogenous H2O2 reduced cell viability in a proportion to the concentration via apoptosis. EDV protected HaCaT cells and HDFs from H2O2 induced reactive oxygen species cell damage and apoptosis. In the mouse model, EDV with fibrin resulted in less necrotic areas and increased angiogenesis on postoperative day 5, compared to sham-treated mice. Our results indicate that EDV could protect H2O2-induced cellular injury via inhibiting early apoptosis and inflammation and also increasing angiogenesis. EDV might be valuable in the treatment of diabetic wounds that oxidative stress has been implicated.

2021 ◽  
Vol 14 (4) ◽  
pp. 301
Author(s):  
Yayoi Kawano ◽  
Viorica Patrulea ◽  
Emmanuelle Sublet ◽  
Gerrit Borchard ◽  
Takuya Iyoda ◽  
...  

Hyaluronic acid (HA) has been known to play an important role in wound healing process. However, the effect of molecular weight (MW) of exogenously administered HA on the wound healing process has not been fully understood. In this study, we investigated HA with different MWs on wound healing process using human epidermal keratinocytes and dermal fibroblasts. Cell proliferation and migration ability were assessed by water soluble tetrazolium (WST) assay and wound scratch assay. We examined the effect of HA addition in a full-thickness wound model in mice and the gene expression related to wound healing. Proliferation and migration of HaCaT cells increased with the increase of MW and concentration of HA. Interleukin (IL-1β), IL-8 and vascular endothelial growth factor (VEGF) as well as matrix metalloproteinase (MMP)-9 and MMP-13 were significantly upregulated by high molecular weight (HMW) HA in keratinocytes. Together with VEGF upregulation and the observed promotion of HaCaT migration, HA with the MW of 2290 kDa may hold potential to improve re-epithelialization, a critical obstacle to heal chronic wounds.


1999 ◽  
Vol 69 (2) ◽  
pp. 113-119 ◽  
Author(s):  
Weimann ◽  
Hermann

The effect of calcium D-pantothenate on the migration, proliferation and protein synthesis of human dermal fibroblasts from three different donors was investigated. The migration of cells into a wounded area was dose-dependently stimulated by Ca D-pantothenate. The number of cells that migrated across the edge of the wound increased from 32 ± 7 cells/ mm without Ca D-pantothenate to 76 ± 2 cells/ mm with 100 mg/ml Ca D-pantothenate. Moreover, the mean migration distance per cell increased from 0.23 ± 0.05 mm to 0.33 ± 0.02 mm. The mean migration speed was calculated to be 10.5 mm/hour without and 15 mm/hour with Ca D-pantothenate. Cell proliferation was also dose-dependently stimulated. The final cell densities were 1.2 to 1.6-fold higher in cultures containing 100 mg/ml Ca D-pantothenate. The protein synthesis was modulated, since two unidentified proteins were more strongly expressed in pantothenate supplemented cultures. In conclusion, Ca D-pantothenate accelerates the wound healing process by increasing the number of migrating cells, their distance and hence their speed. In addition, cell division is increased and the protein synthesis changed. These results suggest that higher quantities of pantothenate are locally required to enhance wound healing.


Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1795
Author(s):  
Judith Salas-Oropeza ◽  
Manuel Jimenez-Estrada ◽  
Armando Perez-Torres ◽  
Andres Eliu Castell-Rodriguez ◽  
Rodolfo Becerril-Millan ◽  
...  

Bursera morelensis is used in Mexican folk medicine to treat wounds on the skin. It is an endemic tree known as “aceitillo”, and the antibacterial and antifungal activity of its essential oil has been verified; it also acts as an anti-inflammatory. All of these reported biological activities make the essential oil of B. morelensis a candidate to accelerate the wound-healing process. The objective was to determine the wound-healing properties of B. morelensis’ essential oil on a murine model. The essential oil was obtained by hydro-distillation, and the chemical analysis was performed by gas chromatography-mass spectrometry (GC-MS). In the murine model, wound-healing efficacy (WHE) and wound contraction (WC) were evaluated. Cytotoxic activity was evaluated in vitro using peritoneal macrophages from BALB/c mice. The results showed that 18 terpenoid-type compounds were identified in the essential oil. The essential oil had remarkable WHE regardless of the dose and accelerated WC and was not cytotoxic. In vitro tests with fibroblasts showed that cell viability was dose-dependent; by adding 1 mg/mL of essential oil (EO) to the culture medium, cell viability decreased below 80%, while, at doses of 0.1 and 0.01 mg/mL, it remained around 90%; thus, EO did not intervene in fibroblast proliferation, but it did influence fibroblast migration when wound-like was done in monolayer cultures. The results of this study demonstrated that the essential oil was a pro-wound-healing agent because it had good healing effectiveness with scars with good tensile strength and accelerated repair. The probable mechanism of action of the EO of B. morelensis, during the healing process, is the promotion of the migration of fibroblasts to the site of the wound, making them active in the production of collagen and promoting the remodeling of this collagen.


2019 ◽  
Vol 2019 ◽  
pp. 1-20 ◽  
Author(s):  
Sarah D’Alessandro ◽  
Andrea Magnavacca ◽  
Federica Perego ◽  
Marco Fumagalli ◽  
Enrico Sangiovanni ◽  
...  

Wound healing is a complex process regulated by multiple signals and consisting of several phases known as haemostasis, inflammation, proliferation, and remodelling. Keratinocytes, endothelial cells, macrophages, and fibroblasts are the major cell populations involved in wound healing process. Hypoxia plays a critical role in this process since cells sense and respond to hypoxic conditions by changing gene expression. This study assessed the in vitro expression of 77 genes involved in angiogenesis, metabolism, cell growth, proliferation and apoptosis in human keratinocytes (HaCaT), microvascular endothelial cells (HMEC-1), differentiated macrophages (THP-1), and dermal fibroblasts (HDF). Results indicated that the gene expression profiles induced by hypoxia were cell-type specific. In HMEC-1 and differentiated THP-1, most of the genes modulated by hypoxia encode proteins involved in angiogenesis or belonging to cytokines and growth factors. In HaCaT and HDF, hypoxia mainly affected the expression of genes encoding proteins involved in cell metabolism. This work can help to enlarge the current knowledge about the mechanisms through which a hypoxic environment influences wound healing processes at the molecular level.


2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Naofumi Tamaki ◽  
Rita Cristina Orihuela-Campos ◽  
Makoto Fukui ◽  
Hiro-O Ito

The wound healing process attempts to restore the integrity and function of the injured tissue. Additionally, proinflammatory cytokines, growth factors, and oxidative stress play important roles in wound healing. The aim of this study was to determine whether hydrogen-rich water intake induces the activation of the Nrf2/antioxidant defense pathway in rat palatal tissue, thereby reducing systemic oxidative stress and proinflammatory cytokine levels and promoting healing-associated genes. A circular excisional wound was created in the oral palatal region, and the wound healing process was observed. The rats were divided into two experimental groups in which either hydrogen-rich water or distilled water was consumed. In the drinking hydrogen-rich water, the palatal wound healing process was accelerated compared to that in the control group. As molecular hydrogen upregulated the Nrf2 pathway, systemic oxidative stresses were decreased by the activation of antioxidant activity. Furthermore, hydrogen-rich water intake reduced proinflammatory cytokine levels and promoted the expression of healing-associated factors in rat palatal tissue. In conclusion, hydrogen-rich water intake exhibited multiple beneficial effects through activation of the Nrf2/antioxidant defense pathway. The results of this study support the hypothesis that oral administration of hydrogen-rich water benefits the wound healing process by decreasing oxidative stress and inflammatory responses.


Author(s):  
Javier Aragoneses ◽  
Ana Suárez ◽  
Cinthia Rodríguez ◽  
Juan Manuel Aragoneses

Acellular dermal matrix grafts (ADMG) have been used as soft tissue graft substitutes for autografts in periodontal plastic surgical procedures. They have benefits like avoiding a second surgical site and patient morbidity that have been associated with autografts, but there is limited evidence available on their tissue response and wound healing process. This histomorphometric animal model study was carried out in mini pigs and it aimed to compare the two types of ADMG materials of porcine derivative with a control group through observation of parameters like epithelial and Keratinized layer thickness, angiogenesis, cellularity, matrix resorption, and inflammatory infiltrate. The surgical technique involved punctures on the edentulous areas stripping the epithelial tissue and exposing the underlying connective tissue, placement of the ADMGs in the appropriate control and test sites. Following this, gingival biopsies were procured at three different time intervals of 15, 45, and 90 days. There were significant differences in epithelial and Keratinized layer thickness among the three groups. This study concluded that there was no clear consensus on which graft material was superior but it gave an insight into the tissue response and wound healing process associated with the graft materials.


2020 ◽  
Vol 16 (1) ◽  
pp. 1
Author(s):  
Maharani Laillyza Apriasari ◽  
Marina Arum Syahadati ◽  
Amy Nindia Carabelly

Abstract: Toman fish contains albumin and omega-6 fatty acid that are instrumental in the healing process of diabetes mellitus (DM) wound. People with DM usually have a prolonged wound healing process. Albumin controls the osmotic pressure, the development of granulation tissue, gives the energy to re-epithelialisation process and collagen base material. Omega-6 fatty acid interrupts phagocytosis induced by neutrophil cells. It increases the action of machropage cell, so that Toman fish can be used as an alternative in accelerating the DM wound healing process. The purpose of this research is to prove the effect of Toman fish extract at 16 mL/ KgBW rat dosage per oral on wound length and contraction on the back of wistar rat (Rattus novergiucs) with DM for 14 days. It was the experimental with a posttest only with control group design  used 12 wistar rat that were divided into 3 groups; the group of Toman fish extract with dose 16 mL/ Kg BW rat, positive control group using Haruan extract with dose 13,54 mL/ Kg BW rat and negative control group using Comfeed BR2 feed. One-way ANOVA test result for wound length and contraction (p= 0,000). The result Post-hoc Least Significant Difference test for wound length and contraction shows that there are significant differences between the group of Toman fish extract and Haruan fish extract (p= 0,000). There is also significant difference between the group of Toman fish extract and Comfeed BR2 feed (p= 0,000). There is no significant difference between the group of Haruan fish extract and Comfeed BR2 feed (p= 0,930). The research concluded that Toman fish extract at 16 mL/ Kg BW rat dosage affects the length and contraction of diabetic mellitus wound. Keywords: Channa micropeltes, clinical analysis, diabetes mellitus, wound


2018 ◽  
Vol 36 (1) ◽  
pp. 40
Author(s):  
Nada Hanifah ◽  
Yusuf Farid Achmad ◽  
Mellya Permatasari ◽  
Marista Kurniati ◽  
Ditya Tiwi Syafira ◽  
...  

Sea Cucumber (Stichopus sp) belongs to Holothuroidea family. Sea Cucumber has lot of uses in the medicine sector, such as: for wound healing, anti-biotic, anti-bacteria, anti-tumor, and anti-coagulation. Diabetes mellitus is a disease characterized by high blood sugar levels with metabolic disorders. This disease can cause wounds called gangrene This research has purpose to prove the influence of giving nano spray of sea cucumber extract within 14 days. In the in vitro examination found 40% concentration of sea cucumber extract which is effective to resist the growth of Methicillin Resistant Staphylococcus aureus bacteria and examined to wistar mouse which are already diabetic inducted with Streptozotocin (STZ) and hurt with punch biopsy with the diameter of 0,8 cm on its back and the wound is infected with bacteria which is intradermal injected. Divided into 3 groups : (K-) no medical treatment, nano spray of sea cucumber extract (T), Nano spray penicillin (K+) to wistar mouse towards the speed of diabetic mellitus wound healing which is infected by Methicillin Resistant Staphylococcus aureus bacteria. Parameter used to measure the rate of wound healing is wound size and hitopathology examination.After it’s regularly given the medicine, the result of nano spray sea cucumber extract 40 % concetration category treatment on wound healing process the diameter of wound on the 3rd day 0.8 cm , on the 7th day 0.4 cm and on the 14th day  wound fully recover according to macros (wound size) and histopathology examination shows faster and better healing compared to treatment category of nano spray penicillin and control marked by score cell and lymphocyte in a small quantity.


2018 ◽  
pp. 116-124
Author(s):  
Damsir Eni Ungke

Diabetic injury is one form of chronic complications. Diabetes mellitus is an open wound on the skin surface that can be accompanied by local tissue death. Diabetes mellitus patients at risk of 29 times the occurrence of diabetic injuries. Diabetic injury is an open wound on the skin surface caused by the presence of macroangiopathy resulting in vascular insusifiensi and neuropati. Organs most often affected by diabetes mellitus complications include the leg blood vessels. Disorders of blood vessels that often occur in diabetes that is on the legs and feet. This study aims to determine the effectiveness of wound care using modern bandage (Metcofazin) on diabetic wound healing process at Emergency Hospital (IGD) Arifin Nu'mang Hospital of Sidrap Regency, and to know the effectiveness of wound care using conventional dressing (normal saline saline NaCl 0 , 9% and gauze bandage) to diabetic wound healing process at Emergency Injury Installation (IGD) Arifin Nu'mang Hospital of Sidrap Regency. The type of research used by the researcher is qualitative research with case study approach. This research has been conducted on 21 November until December 21, 2014 at the Emergency Installation (IGD) Arifin Nu'mang Hospital, Sidrap Regency. Samples used in this study are patients with diabetic injuries at Arifin Nu'mang Hospital Sidrap District with sampling technique by puposive sampling. The results of this study indicate that the treatment of luk a using a modern bandage (metcofazine) is more effective than wound care using conventional dressing (normal saline 0.9% NaCl saline and gauze dressing) on ​​diabetic wound healing process at Arifin Nu'mang Hospital Sidrap Hospital.


2021 ◽  
Vol 22 (11) ◽  
pp. 5571
Author(s):  
Jaeyoon Kim ◽  
Jae Young Shin ◽  
Yun-Ho Choi ◽  
So Young Lee ◽  
Mu Hyun Jin ◽  
...  

Adenosine is a cellular metabolite with diverse derivatives that possesses a wide range of physiological roles. We investigated the molecular mechanisms of adenosine and cordycepin for their promoting effects in wound-healing process. The mitochondrial energy metabolism and cell proliferation markers, cAMP responsive element binding protein 1 (CREB1) and Ki67, were enhanced by adenosine and cordycepin in cultured dermal fibroblasts. Adenosine and cordycepin stimulated adenosine receptor signaling via elevated cAMP. The phosphorylation of mitogen-activated protein kinase kinase (MEK) 1/2, mammalian target of rapamycin (mTOR) and glycogen synthase kinase 3 beta (Gsk3b) and Wnt target genes such as bone morphogenetic protein (BMP) 2/4 and lymphoid enhancer binding factor (Lef) 1 were activated. The enhanced gene expression by adenosine and cordycepin was abrogated by adenosine A2A and A2B receptor inhibitors, ZM241385 and PSH603, and protein kinase A (PKA) inhibitor H89, indicating the involvement of adenosine receptor A2A, A2B and PKA. As a result of Wnt/β-catenin pathway activation, the secretion of growth factors such as insulin-like growth factor (IGF)-1 and transforming growth factor beta (TGFβ) 3 was increased, previously reported to facilitate the wound healing process. In addition, in vitro fibroblast migration was also increased, demonstrating their possible roles in facilitating the wound healing process. In conclusion, our data strongly demonstrate that adenosine and cordycepin stimulate the Wnt/β-catenin signaling through the activation of adenosine receptor, possibly promoting the tissue remodeling process and suggest their therapeutic potential for treating skin wounds.


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