Curcumin treatment enhances the repair and regeneration of wounds in mice exposed to hemibody gamma-irradiation

Hemibody irradiation in multiple fractionated doses is frequently used for the treatment of various neoplastic disorders. It produces both acute and late effects on the skin and subcutaneous tissues that have profound implications in the healing of surgical wounds. Because of the crucial practical importance of hemibody radiation exposure associated with skin wounds, it is imperative to investigate the efficacy of cost-effective herbal products in the reconstruction of irradiated wounds. Therefore, the effect of pretreatment of curcumin was studied on the healing of excision wound in mice exposed to 2, 4, 6, or 8 Gy of hemibody gamma-radiation. A full-thickness skin wound was created by removing the skin flap of the dorsum of 8- to 10-week-old Swiss albino mice partially (lower half, below the rib cage) exposed to 2, 4, 6, or 8 Gy of gamma-radiation. The progression of wound contraction was monitored periodically by capturing video images of the wound, where the first image of each wound from different groups was obtained 1 day after wounding and that day was considered as day 0. Eight animals were used in each group at each exposure dose for wound contraction studies. Furthermore, the effect of curcumin on mean healing time after exposure of mice to 2, 4, 6, or 8Gy of hemibody gamma-radiation was also evaluated, where eight animals were used in each group at each exposure dose. Collagen, hexosamine, DNA, nitric oxide, and histologic profiles were also evaluated during the course of healing of excision wounds at days 4, 8, and 12 after irradiation treated or not with curcumin before exposure to 0 or 6 Gy of gamma-radiation. Six animals were used in each group at each interval for each biochemical parameter studied, except for histologic evaluations, where four animals were used in each group at each interval. Exposure of mice to different doses of gamma-radiation resulted in a dose-dependent delay in contraction and wound-healing time of excision wound, whereas curcumin pretreatment caused a significant elevation in the rate of wound contraction and a decrease in the mean wound-healing time. Treatment with curcumin before irradiation enhanced the synthesis of collagen, hexosamine, DNA, nitrite, and nitrate, and histologic assessment of wound biopsy specimens revealed improved collagen deposition and an increase in fibroblast and vascular densities. The authors' study demonstrates that curcumin pretreatment has a conducive effect on the irradiated wound and could be a substantial therapeutic strategy for ameliorating radiation-induced delay in wound repair in cases of radiation-induced skin injuries.     

Effects of Foeniculum vulgare essential oil compounds,fenchone and limonene,on experimental wound healing

We investigated the wound healing efficacy of the Foeniculum vulgare compounds, fenchone and limonene, using an excisional cutaneous wound model in rats. An excision wound was made on the back of the rat and fenchone and limonene were applied topically to the wounds once daily, separately or together, for 10 days. Tissue sections from the wounds were evaluated for histopathology. The healing potential was assessed by comparison to an untreated control group and an olive oil treated sham group. We scored wound healing based on epidermal regeneration, granulation tissue thickness and angiogenesis. After day 6, wound contraction with limonene was significantly better than for the control group. Ten days after treatment, a significant increase was observed in wound contraction and re-epithelialization in both fenchone and limonene oil treated groups compared to the sham group. Groups treated with fenchone and with fenchone + limonene scored significantly higher than the control group, but the difference was not statistically significant compared to the olive oil treated group. Our findings support the beneficial effects of fenchone and limonene for augmenting wound healing. The anti-inflammatory and antimicrobial activities of fenchone and limonene oil increased collagen synthesis and decreased the number of inflammatory cells during wound healing and may be useful for treating skin wounds.     

胎儿早期小鼠无疤痕愈合的数据转录组学分析

已有研究显示,胎龄小于14 d的小鼠胎儿皮肤能够实现无疤痕创伤愈合。深入研究胎儿无疤痕愈合的分子机理,对于伤口护理方法优化与创伤医学的发展至关重要。利用已有数据库进行不同胎龄的小鼠皮肤组织转录组深入挖掘是常用的研究方法之一。从基因表达综合数据库（gene expression omnibus,GEO）在线数据库中寻找适合无疤痕愈合研究的基因表达谱芯片（GSE71619）,其中包含胎龄14 d（E14）、胎龄18 d（E18）和6周龄成年鼠（W6）的皮肤组织样本。分别将无疤痕愈合（E14）与疤痕愈合皮肤组（E18+W6）对比分析,筛选差异表达基因（differential genes,DEGs）,获得了4 654个DEGs（|log2 FC|≥1,P<0.05）。通过维恩图分析和基因功能注释确定了228个候选基因,并分为4个不同的Cluster。进一步重点分析了Cluster 3中涉及的基因：对于E14组,上调基因主要与促进伤口愈合的组织重塑和细胞外基质（extracellular matrix,ECM）形成功能相关。通过蛋白互作网络分析,确定了17个属于胶原家族和成纤维细胞迁移相关基因的关键基因。研究结果揭示了ECM的重塑和成纤维细胞活化在早期妊娠胎儿无疤痕愈合模式中的重要性,并筛选出可能的关键基因,为无疤痕伤口护理和创伤、医美领域提供了重要实验依据。     

Effects of diode laser therapy on the acellular dermal matrix

Acellular dermal matrix (ADM) was subcutaneously implanted into calvarian skin of male Wistar rats (n = 40). Low-level laser (λ 685 nm, 4 J/cm²) was locally applied in experimental group (n = 20) above the skin flap. Grafts were harvested at 1, 3, 7 and 14 days after surgery and underwent histological analyses. In treated animals, the extent of edema and the number of inflammatory cells were reduced (P < 0.05). The amount of collagen in graft treated with low-level laser were significantly higher than those of controls (P < 0.05) and were statistically more prominent on the 14th day after surgery. The mean count of fibroblasts was significantly higher in the low-laser therapy group within the 3rd day, showing a marked influx of fibroblasts into area. In conclusion, wound healing of the ADM appear to be positively affected by laser therapy.     

The effect of disodium cromoglycate on the skin wound healing and collagen content in the wounds of rats

The effect of disodium cromoglycate on skin wound healing and collagen formation in the wounds was studied. Disodium cromoglycate (a mast cell stabilizer) administered to the rats in a dose of 2 mg/animal was found to retard wound healing and markedly increased wound surface in all examined days (3rd, 5th, 7th, 10th, 14th day of healing). The mast cell stabilizer injected directly into wounds decreased collagen content, especially on 10th and 14th day of the healing process.     

Effect of sodium diphenylhydantoin on skin wound healing in rats

This study evaluated the effect of phenytoin (sodium diphenylhydantoin) on skin wound healing in a rat model. The study was divided into two parts. In part I, 20 mul of phenytoin (10 mg/ml) was subcutaneously injected into the 3-cm dorsal full-thickness incisional wounds of 14 rats on postoperative days 0, 3, and 6. Twelve rats that received saline injections were used as the controls. The skin samples were harvested and tested for tensile strength and histology. An additional 12 rats with the same incisional wounds were tested for chemokine gene expressions. In part II, 20 mul of phenytoin (10 mg/ml) was applied topically once a day on a 4 x 4 cm area of the open dorsal wounds of 10 rats. Saline was applied to the wounds of the 10 control group rats. The wounds were measured weekly. The results showed that the average tensile strength of the phenytoin-treated wound was 0.49 +/- 0.08 MPa compared with the control group at 0.02 +/- 0.01 MPa (p < 0.05). The density ratio of chemokine monocyte chemotactic protein (MCP-1) to beta-actin in the phenytoin-treated group was also significantly higher than in the control group (p < 0.05). Histologic analysis of the phenytoin group showed a large amount of fibroblast proliferation, collagen synthesis, and neovascularization. Phenytoin-treated wounds were also smaller at 1 to 6 weeks postoperatively than the control group wounds. The authors conclude that the administration of phenytoin can promote wound healing and significantly increase MCP-1 expression. Phenytoin-treated wounds showed significant increase in collagen deposition and neovascularization, which resulted in an increased wound tensile strength and accelerated healing of both open and closed wounds.     

Combination of Adrenomedullin with Its Binding Protein Accelerates Cutaneous Wound Healing

Cutaneous wound continues to cause significant morbidity and mortality in the setting of diseases such as diabetes and cardiovascular diseases. Despite advances in wound care management, there is still an unmet medical need exists for efficient therapy for cutaneous wound. Combined treatment of adrenomedullin (AM) and its binding protein-1 (AMBP-1) is protective in various disease conditions. To examine the effect of the combination treatment of AM and AMBP-1 on cutaneous wound healing, full-thickness 2.0-cm diameter circular excision wounds were surgically created on the dorsum of rats, saline (vehicle) or AM/AMBP-1 (96/320 μg kg BW) was topically applied to the wound daily and wound size measured. At days 3, 7, and 14, skin samples were collected from the wound sites. AM/AMBP-1 treated group had significantly smaller wound surface area than the vehicle group over the 14-day time course. At day 3, AM/AMBP-1 promoted neutrophil infiltration (MPO), increased cytokine levels (IL-6 and TNF-α), angiogenesis (CD31, VEGF and TGFβ-1) and cell proliferation (Ki67). By day 7 and 14, AM/AMBP-1 treatment decreased MPO, followed by a rapid resolution of inflammation characterized by a decrease in cytokines. At the matured stage, AM/AMBP-1 treatment increased the alpha smooth muscle actin expression (mature blood vessels) and Masson-Trichrome staining (collagen deposition) along the granulation area, and increased MMP-9 and decreased MMP-2 mRNA expressions. TGFβ-1 mRNA levels in AM/AMBP-1 group were 5.3 times lower than those in the vehicle group. AM/AMBP-1 accelerated wound healing by promoting angiogenesis, collagen deposition and remodeling. Treatment also shortened the days to reach plateau for wound closure. Thus, AM/AMBP-1 may be further developed as a therapeutic for cutaneous wound healing.     

局部应用PTD-SOD、SOD对小鼠皮肤创伤的抗氧化应激损伤保护效果及其比较

目的探讨局部应用PTD-SOD、SOD对小鼠皮肤创伤的抗氧化应激损伤保护效果及其差异。方法制备机械性创伤小鼠模型和不同浓度的PTD-SOD(1000、3000、6000 U)及SOD(1000、3000、6000 U)溶液,分别用上述溶液进行治疗,同时设立模型对照组和生理盐水对照组,各组均连续治疗13 d。观察各组创伤愈合情况,记录创伤愈合率和愈合天数;于创伤后第14天取各组小鼠创伤愈合部位皮肤,一部分制成10%组织匀浆液用于检测抗氧化酶(SOD、CAT、GSH-Px)活性及丙二醛(MDA)、羟脯氨酸(Hyp)含量,一部分制成病理组织切片用于皮肤组织学观察。结果①与模型对照组相比,PTD-SOD各组或SOD各组的抗氧化酶活性和Hyp含量显著(P0.05)或极显著(P0.01)升高,MDA含量显著(P0.05)或极显著(P0.01)降低,能显著(P0.05)或极显著(P0.01)提高创伤愈合率、缩短创伤愈合时间;与生理盐水对照组相比,结果类似。②在同等剂量下,从促创伤愈合时间、抗氧化酶活性、MDA含量、Hyp含量等方面比较,PTD-SOD组明显(P0.05)或极明显(P0.01)优于SOD组。③适当剂量的PTD-SOD促创伤愈合效果优于高剂量PTD-SOD的促创伤愈合效果。结论 PTD-SOD或SOD在皮肤创伤治疗中具有良好的抗氧化应激损伤效果,这种保护效果在创伤愈合的早期最显著;同等剂量下,PTD-SOD在促创伤愈合的效果上明显优于SOD。     

Clock gene Per2 modulates epidermal tissue repair in vivo

Wound healing can be influenced by genes that control the circadian cycle, including Per2 and BMAL1, which coordinate the functions of several organs, including the skin. The aim of the study was to evaluate the role of PER2 during experimental skin wound healing. Two groups (control and Per2-KO), consisting of 14 male mice each, were anesthetized by inhalation, and two 6 mm wounds were created on their dorsal skin using a punch biopsy. A silicone ring was sutured around the wound perimeter to restrict contraction. The wound healing process was clinically measured daily (closure index) until complete wound repair. On Day 6, histomorphometric analysis was performed using the length and thickness of the epithelial migration tongue, in addition to counting vessels underlying the lesion by immunofluorescence assay and maturation of collagen fibers through picrosirius staining. Bromodeoxyuridine (BrdU) incorporation and quantification were performed using the subcutaneous injection technique 2 h before euthanasia and through immunohistochemical analysis of the proliferative index. In addition, the qualitative analysis of myofibroblasts and periostin distribution in connective tissue was performed by immunofluorescence. Statistically significant differences were observed in the healing time between the experimental groups (means: 15.5 days for control mice and 13.5 days for Per2-KO; p = 0.001). The accelerated healing observed in the Per2-KO group (p < 0.05) was accompanied by statistical differences in wound diameter and length of the migrating epithelial tongue (p = 0.01) compared to the control group. Regarding BrdU immunoreactivity, higher expression was observed in the intact epithelium of Per2-KO animals (p = 0.01), and this difference compared to control was also present, to a lesser extent, at the wound site (p = 0.03). Immunofluorescence in the connective tissue underlying the wound showed a higher angiogenic potential in the Per2-KO group in the intact tissue area and the wound region (p < 0.01), where increased expression of myofibroblasts was also observed. Qualitative analysis revealed the distribution of periostin protein and collagen fibers in the connective tissue underlying the wound, with greater organization and maturation during the analyzed period. Our research showed that the absence of the Per2 gene positively impacts the healing time of the skin in vivo. This acceleration depends on the increase of epithelial proliferative and angiogenic capacity of cells carrying the Per2 deletion.     

Keratinocytes derived from embryonic stem cells induce wound healing in mice

The skin plays an important role in defending the body against the environment. Treatments for burns and skin injuries that use autologous or allogenic skin grafts derived from adult or embryonic stem cells are promising. Embryonic stem cells are candidates for regenerative and reparative medicine. We investigated the utility of keratinocyte-like cells, which are differentiated from mouse embryonic stem cells, for wound healing using a mouse surgical wound model. Mice were allocated to the following groups: experimental, in which dressing and differentiated cells were applied after the surgical wound was created; control, in which only the surgical wound was created; sham, in which only the dressing was applied after the surgical wound was created; and untreated animal controls with healthy skin. Biopsies were taken from each group on days 3, 5 and 7 after cell transfer. Samples were fixed in formalin, then stained with Masson’s trichrome and primary antibodies to interleukin-8 (IL-8), fibroblast growth factor-2 (FGF-2), monocyte chemoattractant protein-1 (MCP-1), collagen-1 and epidermal growth factor (EGF) using the indirect immunoperoxidase technique for light microscopy. Wound healing was faster in the experimental group compared to the sham and control groups. The experimental group exhibited increased expression of IL-8, FGF-2 and MCP-1 during early stages of wound healing (inflammation) and collagen-1 and EGF expression during late stages of wound healing (proliferation and remodeling). Keratinocytes derived from embryonic stem cells improved wound healing and influenced the wound healing stages.     

Promotive effects of far-infrared ray on full-thickness skin wound healing in rats

The biological effects of far-infrared ray (FIR) on whole organisms remain poorly understood. The aim of our study was to investigate not only the hyperthermic effect of the FIR irradiation, but also the biological effects of FIR on wound healing. To evaluate the effect of FIR on a skin wound site, the speed of full-thickness skin wound healing was compared among groups with and without FIR using a rat model. We measured the skin wound area, skin blood flow, and skin temperature before and during FIR irradiation, and we performed histological inspection. Wound healing was significantly more rapid with than without FIR. Skin blood flow and skin temperature did not change significantly before or during FIR irradiation. Histological findings revealed greater collagen regeneration and infiltration of fibroblasts that expressed transforming growth factor-beta1 (TGF-beta1) in wounds in the FIR group than in the group without FIR. Stimulation of the secretion of TGF-beta1 or the activation of fibroblasts may be considered as a possible mechanisms for the promotive effect of FIR on wound healing independent of skin blood flow and skin temperature.     

Studies on wound healing potential of red pigment isolated from marine Bacterium Vibrio sp.

Wounds are common clinical entities of life which may be subacute or acute. Wound healing is a complex biochemical process where the cell structures are restored to normalcy, which depend on cell proliferation and migration, basically fibroblast cell. The present investigation was undertaken to evaluate the healing efficacy of red pigment isolated from marine isolate Vibrio sps on experimental wounds in albino rats. The red pigment was applied topically, twice daily for 14 days. Treatment with framycetin ointment was used as reference control. The red pigment treated group showed faster reduction in wound area in comparison with control and framycetin ointment treated groups. In conclusion, red pigment possesses significant healing potential in wounds and has a positive influence on the different phases of wound repair.     

A novel composition for in vitro and in vivo regeneration of skin and connective tissues

The particular combination of polydeoxyribonucleotides, l-carnitine, calcium ions, proteolytic enzyme and other ingredients acts in a synergetic way in the regeneration of skin and connective tissues. This new formulation of active principles was tested in vitro as a cell and tissue culture medium and in vivo for various preparations in support of tissue regeneration. In vitro, the new blend allowed the maintenance of skin biopsies for more than 1 year in eutrophic conditions. Immunocytochemical analyses of fibroblasts isolated from these biopsies confirmed a significant increase of the epidermal and connective wound-healing markers such as collagen type I, collagen type IV, cytokeratin 1 (CK1), CK5, CK10 and CK14 versus controls. To examine the effects of the new compound in vivo, we studied impaired wound healing in genetically diabetic db/db mice. At day 18, diabetic mice treated with the new composition showed 100% closure of wounds and faster healing than mice treated with the other solutions. This complex of vital continuity factors or life-keeping factors could be used as a tissue-preserving solution or a cosmetic/drug/medical device to accelerate wound healing in the treatment of patients with deficient wound repair to promote the regeneration of cutaneous and connective tissues (injuries-wound, dermatitis) and prevent the recurrent relapses.     

Atropa belladonna L. water extract: modulator of extracellular matrix formation in vitro and in vivo

Previously, we found that treatment of cutaneous wounds with Atropa belladonna L. (AB) revealed shortened process of acute inflammation as well as increased tensile strength and collagen deposition in healing skin wounds (Gál et al. 2009). To better understand AB effect on skin wound healing male Sprague-Dawley rats were submitted to one round full thickness skin wound on the back. In two experimental groups two different concentrations of AB extract were daily applied whereas the control group remained untreated. For histological evaluation samples were removed on day 21 after surgery and stained for wide spectrum cytokeratin, collagen III, fibronectin, galectin-1, and vimentin. In addition, in the in vitro study different concentration of AB extract were used to evaluate differences in HaCaT keratinocytes proliferation and differentiation by detection of Ki67 and keratin-19 expressions. Furthermore, to assess ECM formation of human dermal fibroblasts on the in vitro level fibronectin and galectin-1 were visualized. Our study showed that AB induces fibronectin and galectin-1 rich ECM formation in vitro and in vivo. In addition, the proliferation of keratinocytes was also increased. In conclusion, AB is an effective modulator of skin wound healing. Nevertheless, further research is needed to find optimal therapeutic concentration and exact underlying mechanism of action.     

高乳清蛋白的肠内营养对大鼠伤口愈合的影响

探讨高乳清蛋白的肠内营养对大鼠创伤皮肤的促愈合作用.将36只SD大鼠随机分为3组,每组12只,即高乳清蛋白肠内营养组(A)、普通肠内营养组(B)、空白对照组(C),建立大鼠皮肤创伤模型后进行肠内营养支持,肠内营养用量为每天731.5kJ·kg-1,以灌胃的方式提供,分别于术后第7、14天测定血清蛋白、血红蛋白含量并计算创面愈合率.结果显示,术后第7、14天A组的血清蛋白、血红蛋白及伤口皮肤平均愈合率显著高于B、C组,差异具有统计学意义(p＜0.05).表明高乳清蛋白肠内营养具有较好的促进伤口愈合的作用.     

Neurotensin-loaded collagen dressings reduce inflammation and improve wound healing in diabetic mice

Impaired wound healing is an important clinical problem in diabetes mellitus and results in failure to completely heal diabetic foot ulcers (DFUs), which may lead to lower extremity amputations. In the present study, collagen based dressings were prepared to be applied as support for the delivery of neurotensin (NT), a neuropeptide that acts as an inflammatory modulator in wound healing. The performance of NT alone and NT–loaded collagen matrices to treat wounds in streptozotocin (STZ) diabetic induced mice was evaluated. Results showed that the prepared dressings were not-cytotoxic up to 72 h after contact with macrophages (Raw 264.7) and human keratinocyte (HaCaT) cell lines. Moreover, those cells were shown to adhere to the collagen matrices without noticeable change in their morphology. NT–loaded collagen dressings induced faster healing (17% wound area reduction) in the early phases of wound healing in diabetic wounded mice. In addition, they also significantly reduced inflammatory cytokine expression namely, TNF-α (p < 0.01) and IL-1β (p < 0.01) and decreased the inflammatory infiltrate at day 3 post-wounding (inflammatory phase). After complete healing, metalloproteinase 9 (MMP-9) is reduced in diabetic skin (p < 0.05) which significantly increased fibroblast migration and collagen (collagen type I, alpha 2 (COL1A2) and collagen type III, alpha 1 (COL3A1)) expression and deposition. These results suggest that collagen-based dressings can be an effective support for NT release into diabetic wound enhancing the healing process. Nevertheless, a more prominent scar is observed in diabetic wounds treated with collagen when compared to the treatment with NT alone.     

Stereological and gene expression examinations on the combined effects of photobiomodulation and curcumin on wound healing in type one diabetic rats

We examined the effects of photobiomodulation (PBM) independently and combined with curcumin on stereological parameters and basic fibroblast growth factor (bFGF), hypoxia-inducible factor-1α (HIF-1α), and stromal cell-derived factor-1α (SDF-1α) gene expressions in an excisional wound model of rats with type one diabetes mellitus (T1DM). T1DM was induced by an injection of streptozotocin (STZ) in each of the 90 male Wistar rats. One round excision was generated in the skin on the back of each of the 108 rats. The rats were divided into six groups (n = 18 per group): control (diabetic), untreated group; vehicle (diabetic) group, which received sesame oil; PBM (diabetic) group; curcumin (diabetic) group; PBM + curcumin (diabetic) group; and a healthy control group. On days 4, 7, and 15, we conducted both stereological and quantitative real-time PCR (qRT-PCR) analyses. The PBM and PBM + curcumin groups had significantly better inflammatory response modulation in terms of macrophages (P < .01), neutrophils (P < .001), and increased fibroblast values compared with the other groups at day 4 (P < .001), day 7 (P < .01), and day 15 (P < .001). PBM treatment resulted in increased bFGF gene expression on days 4 (P < .001) and 7 (P < .001), and SDF-1α gene expression on day 4 (P < .001). The curcumin group had increased bFGF (P < .001) expression on day 4. Both the PBM and PBM + curcumin groups significantly increased wound healing by modulation of the inflammatory response, and increased fibroblast values and angiogenesis. The PBM group increased bFGF and SDF-1α according to stereological and gene expression analyses compared with the other groups. The PBM and PBM + curcumin groups significantly increased the skin injury repair process to more rapidly reach the proliferation phase of the wound healing in T1DM rats.     

Sustained-release adrenomedullin ointment accelerates wound healing of pressure ulcers

Pressure ulcers are one of the most common complications in elderly, incontinent or paralyzed patients. For the healing of pressure ulcers, the development of granulation tissue and reepithelialization is required. Adrenomedullin (AM), an endogenous vasodilator peptide, is reported to stimulate the proliferation and migration of various cells including endothelial cells, fibroblasts and keratinocytes. Therefore, we hypothesized that AM might accelerate the healing process of pressure ulcers in which these cells were involved. We developed a sustained-release ointment containing human recombinant AM, and applied it in a mouse model of pressure ulcer twice a day for 14 days. Human AM was efficiently absorbed in wound area, but its blood concentration was negligible. AM ointment significantly reduced the wound area on day 5 to 7 after injury. In addition, AM ointment accelerated the formation of granulation tissue and angiogenesis as well as lymphangiogenesis after 7 days of treatment. Immunological analysis revealed that Ki-67-positive proliferating cells in granulation tissue expressed AM receptors. In summary, sustained-release AM significantly improved wound healing of pressure ulcers through acceleration of granulation and induction of angiogenesis and lymphangiogenesis. Therefore, sustained-release AM ointment may be a novel therapeutic agent for pressure ulcers.     

Effect of topically applied steroidal and nonsteroidal anti-inflammatory agents on skin repair and regeneration

We studied the effects of topically applied steroidal and nonsteroidal anti-inflammatory agents on dermal and epidermal wound healing. Superficial wounds (0.3 mm deep) on the skin of domestic pigs were treated daily with either 0.1% triamcinolone acetonide (TA), 1% hydrocortisone (HC), 1% nandrolone decanoate (ND), 1% ND + 0.1% TA, 10 mg ibuprofen, 10 mg meclofenamate sodium, 3 mg indomethacin, vehicle (USP petrolatum or 70% ethanol), or control (untreated). Wounds were excised on days 2-7 after wounding and the epidermis was separated from the dermis. The dermis was assayed for collagen biosynthesis and the epidermis was evaluated for reepithelialization. A significant decrease (P less than 0.01) in relative collagen synthesis was observed in the wounded dermis in both HC- and TA-treated groups on day 3 after wounding, but there were no significant differences on days 4-7. Depressed collagen and noncollagenous protein production was also noted in vehicle-treated wounds on day 3. Topical application of ND did not affect collagen synthesis, but when combined with TA it eliminated the inhibitory effect observed as a result of TA alone. Topical ND accelerated wound reepithelialization by 12.5% compared with vehicle and by 26% compared with untreated controls. TA delayed epidermal resurfacing by 22%, but when combined with ND (ND + TA) the rate of reepithelialization was similar to vehicle-treated wounds. HC enhanced resurfacing when compared with untreated wounds but did not differ markedly from its vehicle. The nonsteroidal anti-inflammatory drugs when topically applied markedly reduced inflammation (erythema, heat, and edema) but did not influence the healing process.     

Negative effects of a low-quality protein diet on wound healing via modulation of the MMP2 activity in rats

Protein malnutrition is largely associated with a delay or failure of the healing process. However, the effect of dietary protein quality on wound healing is largely unknown. This study aimed to reveal the effect of dietary protein quality on wound healing and elucidate the regulatory mechanisms in a rat model of full-thickness cutaneous wounds. Rats were fed a normal diet for a week, and then they were divided into three groups that were fed the following diet for the experimental period: casein diet, gluten diet and gluten + lysine diet. The gluten diet significantly decreased body weight and wound healing compared with the casein diet, but this effect was reversed by supplementation with lysine. The numbers of leukocytes were significantly higher in the skin of the gluten group than those in the casein group. The wounded skin tissues of the gluten group showed lower amounts of collagen deposition compared with that in the casein group. Our results also showed that both matrix metalloproteinase (MMP) 2 activity and MMP14 mRNA levels were significantly increased in the skin of the gluten group, compared with the casein group. In summary, this study suggests low-quality protein diets have negative effects on wound healing via modulation of MMP2 activity in rats.