RESUMEN
The skin is a critical organ for the maintenance of the integrity and protection of the organism. When a wound occurs, a sequence of healing mechanisms is triggered to reconstruct the wounded area. ß-caryophyllene is a sesquiterpene in Copaifera langsdorffii oleoresin with antioxidant and anti-inflammatory potential. On the basis of previous studies with C. langsdorffii, ß-caryophyllene was selected to evaluate its wound healing potential and pharmacological mechanisms. The excision wound model was used with male Wistar rats and macroscopic, histological, immunohistochemical and biochemical analyses were performed with skin samples, comparing the ß-caryophyllene-treated group with reference drugs. The results showed macroscopic retraction of the wounds treated with ß-caryophyllene. Biochemical assays revealed the antioxidant and anti-inflammatory mechanisms of the ß-caryophyllene-treated group with increasing levels of IL-10 and GPx and decreasing levels of pro-inflammatory molecules, including TNF-α, IFN-γ, IL-1ß and IL-6. After ß-caryophyllene treatment, immunohistochemical assays showed enhanced re-epithelialization, through the increase in laminin-γ2 and desmoglein-3 immunolabeling. ß-caryophyllene also act in the remodeling mechanism, increasing the collagen content in the Masson's trichrome staining. These findings indicated the wound-healing potential of ß-caryophyllene topical formulation in rat skin wounds, mediated by antioxidant, anti-inflammatory and re-epithelialization mechanisms.
Asunto(s)
Antiinflamatorios no Esteroideos/administración & dosificación , Antioxidantes/administración & dosificación , Fabaceae/química , Fitoquímicos/administración & dosificación , Fitoterapia/métodos , Extractos Vegetales/administración & dosificación , Sesquiterpenos Policíclicos/administración & dosificación , Repitelización/efectos de los fármacos , Piel/lesiones , Cicatrización de Heridas/efectos de los fármacos , Heridas Penetrantes/tratamiento farmacológico , Administración Tópica , Animales , Citocinas/metabolismo , Masculino , Modelos Animales , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacos , Resultado del Tratamiento , Heridas Penetrantes/metabolismoRESUMEN
Estrogenic steroids and adenosine A2A receptors promote the wound healing and angiogenesis processes. However, so far, it is unclear whether estrogen may regulate the expression and pro-angiogenic activity of A2A receptors. Using in vivo analyses, we showed that female wild type (WT) mice have a more rapid wound healing process than female or male A2A-deficient mice (A2AKO) mice. We also found that pulmonary endothelial cells (mPEC) isolated from female WT mice showed higher expression of A2A receptor than mPEC from male WT mice. mPEC from female WT mice were more sensitive to A2A-mediated pro-angiogenic response, suggesting an ER and A2A crosstalk, which was confirmed using cells isolated from A2AKO. In those female cells, 17ß-estradiol potentiated A2A-mediated cell proliferation, an effect that was inhibited by selective antagonists of estrogen receptors (ER), ERα, and ERß. Therefore, estrogen regulates the expression and/or pro-angiogenic activity of A2A adenosine receptors, likely involving activation of ERα and ERß receptors. Sexual dimorphism in wound healing observed in the A2AKO mice process reinforces the functional crosstalk between ER and A2A receptors.
Asunto(s)
Estradiol/farmacología , Receptor alfa de Estrógeno/genética , Receptor beta de Estrógeno/genética , Neovascularización Fisiológica/efectos de los fármacos , Receptor de Adenosina A2A/genética , Heridas Penetrantes/genética , Adenosina/análogos & derivados , Adenosina/farmacología , Animales , Proliferación Celular/efectos de los fármacos , Células Endoteliales/citología , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Receptor alfa de Estrógeno/antagonistas & inhibidores , Receptor alfa de Estrógeno/metabolismo , Receptor beta de Estrógeno/antagonistas & inhibidores , Receptor beta de Estrógeno/metabolismo , Femenino , Regulación de la Expresión Génica , Pulmón/citología , Pulmón/metabolismo , Masculino , Ratones , Ratones Noqueados , Neovascularización Fisiológica/genética , Fenetilaminas/farmacología , Pirazoles/farmacología , Pirimidinas/farmacología , Receptor Cross-Talk , Receptor de Adenosina A2A/metabolismo , Factores Sexuales , Transducción de Señal , Cicatrización de Heridas/efectos de los fármacos , Cicatrización de Heridas/genética , Heridas Penetrantes/tratamiento farmacológico , Heridas Penetrantes/metabolismo , Heridas Penetrantes/patologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Sorocea guilleminina Gaudich. is a tree or shrub endemic to Brazil. Its leaves are used in Brazilian folk medicine for the healing of wounds, stomach problems, inflammation and as diuretic. The present study evaluates the activity and action mechanisms of the healing properties of the aqueous extract of S. guilleminiana leaves (AESg), in experimental models in vivo and in vitro, as well as performs a phytochemical analysis of the extract. MATERIALS AND METHODS: The AESg was prepared by infusion: Ten g of dry leaves powder in 1â¯L hot water, soaked for 15â¯min, filtered, lyophilized, and stored at -30⯰C. Phytochemical analyses were realized by colorimetry and HPLC/ESI/MS. Its' in vitro cytotoxicity was evaluated on fibroblastic N3T3 cells. The potential of the wound healing activity in vivo was evaluated using excision and incision wound rat models, by histopathology of the injured skin along with the determination of nitric oxide, cytokines (IL-1ß, IL-10, and TNF-α), and antioxidant parameters (GSH, MPO and CAT). In vitro wound healing activity was also demonstrated in scratched N3T3 cells, by measuring the proliferation/migration rate. RESULTS: The phytochemical analysis of the AESg revealed a strong presence of polar compounds, especially flavonoids (4 majoritarian), as well as terpenes and/or sterols (2 majoritarian). The AESg showed no toxicity in the N3T3 cell line (IC50â¯>â¯800⯵g/mL). Topical treatment with the AESg showed an increase (pâ¯<â¯0.05) in wound contraction with 2â¯mg/g cream on days 5 and 9 (43.56% and 6.70% increase, respectively), and with 50â¯mg/g on days 7 and 9 (10.88% and 7.91%, respectively), compared to the vehicle (non-ionic neutral cream). Topical application of AESg (2 or 50â¯mg/g non-ionic cream) in incised wounds caused an increase in the force necessary for the rupture of the wound when compared to the vehicle group. No changes in cytokines (IL-1ß, IL-10, or TNF-α) or NO accumulation was found with up to 50â¯mg/g AESg treatment. For antioxidant activity on the incision wound, an increase in GSH levels was denoted with the AESg use, at the lowest and highest dose (2 and 50â¯mg/g) by 75.86% and 61.20% respectively, when compared to the vehicle. Also, the CAT activity was accentuated by AESg at the highest dose (50â¯mg/g) by 85.87%. Finally, the AESg at all doses attenuated MPO activity significantly in the incision wound by 71.35%, 73.21%, 78.08%, respectively. In the scratch test on N3T3 cells, the treatment with AESg resulted also in an increase in fibroblast proliferation/migration rate, compared to the vehicle. CONCLUSION: AESg is not cytotoxic. The results confirm the popular use of the leaf infusion of S. guilleminiana for the treatment of cutaneous wounds, possibly by stimulating the proliferation of fibroblasts with a consequent deposition of collagen, fastening rearrangement of collagen fibers, and greater transformation into myofibroblasts, essential in the healing process. Preliminary chemical analyzes of AESg revealed the presence mainly of phenolic compounds, being salicylic acid, gallic acid, pinocembrin and isoquercitrin the majoritarian ones.
Asunto(s)
Moraceae , Extractos Vegetales/farmacología , Hojas de la Planta , Piel/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Heridas Penetrantes/tratamiento farmacológico , Animales , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Citocinas/metabolismo , Modelos Animales de Enfermedad , Ratones , Moraceae/química , Células 3T3 NIH , Óxido Nítrico/metabolismo , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/toxicidad , Hojas de la Planta/química , Ratas Wistar , Repitelización/efectos de los fármacos , Piel/lesiones , Piel/metabolismo , Piel/patología , Heridas Penetrantes/metabolismo , Heridas Penetrantes/patologíaRESUMEN
Calreticulin is an endoplasmic reticulum-resident, calcium-binding, stress-produced, chaperone protein that serves multiple functions and is widely distributed in eukaryotic cells. Exogenously applied recombinant calreticulin solution, markedly enhanced the rate and quality of skin wound healing. These modulatory effects are more efficient than commercially available topic platelet-derived growth factor ointments (Regranex®). Trypanosoma cruzi calreticulin is more effective in equimolar terms to human counterpart in accelerating skin wound healing. While the effect of externally added recombinant parasite calreticulin on wound healing has been reported, the domains responsible for these modulatory effects have not yet been established. Here, recombinant parasite calreticulin and some of its domains were tested to assess their influence in increasing proliferation and migration of fibroblasts in vitro and rat skin wound healing in vivo. Herein, we propose that Trypanosoma cruzi whole calreticulin or some of its domains are differentially involved in the modulation of wound-healing cell migration and proliferation, and cosmetic outcome. Therefore, precise combination of the parasite protein and its domains could allow us to tailor-specific desired effects during the skin wound-healing process.
Asunto(s)
Calreticulina/farmacología , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Fragmentos de Péptidos/farmacología , Proteínas Protozoarias/farmacología , Piel/efectos de los fármacos , Trypanosoma cruzi/metabolismo , Cicatrización de Heridas/efectos de los fármacos , Heridas Penetrantes/tratamiento farmacológico , Animales , Calreticulina/genética , Calreticulina/metabolismo , Células Cultivadas , Modelos Animales de Enfermedad , Fibroblastos/metabolismo , Fibroblastos/patología , Masculino , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/metabolismo , Dominios Proteicos , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , Ratas Sprague-Dawley , Proteínas Recombinantes/farmacología , Piel/lesiones , Piel/metabolismo , Piel/patología , Trypanosoma cruzi/genética , Heridas Penetrantes/metabolismo , Heridas Penetrantes/patologíaRESUMEN
Here, we evaluate the anti-inflammatory and wound-healing effects of methanolic crude extract obtained from aerial parts (leaves and branches) of Rubus imperialis Chum. Schl. (Rosaceae) and the pure compound niga-ichigoside F1. Anti-inflammatory activity was determined in vivo and in vitro, and the healing effect was evaluated in surgical lesions in mice skin. The 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) assay and H2O2-induced oxidative stress were used to determine antioxidant activity. The efferocytosis activity was also determined. The data obtained show that the extract of R. imperialis promote reduction in the inflammatory process induced by lipopolysaccharide (LPS) or carrageenan in the air pouch model; the effects could be reinforced by nitric oxide reduction in LPS-stimulated neutrophils, and an increase in the efferocytosis. The extract showed wound healing property in vitro and in vivo, scavenging activity for DPPH, and cytoprotection in the H2O2-induced oxidative stress in L929 cells. In addition, the compound niga-ichigoside F1 was able to reduce the NO secretion; however, it did not present wound-healing activity in vitro. Together, the data obtained point out the modulatory actions of R. imperialis extract on leukocyte migration to the inflamed tissue, the antioxidant, and the pro-resolutive activity. However, the R. imperialis anti-inflammatory activity may be mediated in parts by niga-ichigoside F1, and on wound healing do not correlated with niga-ichigoside F1.
Asunto(s)
Antiinflamatorios/farmacología , Antioxidantes/farmacología , Inflamación/prevención & control , Extractos Vegetales/farmacología , Rubus , Saponinas/farmacología , Piel/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Heridas Penetrantes/tratamiento farmacológico , Animales , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Compuestos de Bifenilo/química , Carragenina , Línea Celular , Quimiotaxis de Leucocito/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Peróxido de Hidrógeno/farmacología , Inflamación/inducido químicamente , Inflamación/metabolismo , Lipopolisacáridos , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/metabolismo , Masculino , Metanol/química , Ratones Endogámicos BALB C , Infiltración Neutrófila/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Estrés Oxidativo/efectos de los fármacos , Fitoterapia , Picratos/química , Componentes Aéreos de las Plantas , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Plantas Medicinales , Rubus/química , Saponinas/química , Saponinas/aislamiento & purificación , Piel/lesiones , Piel/metabolismo , Piel/patología , Solventes/química , Heridas Penetrantes/metabolismo , Heridas Penetrantes/patologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Struthanthus vulgaris (Vell.) Mart. (Loranthaceae) has been largely used in traditional folk medicine in Brazil as an anti-inflammatory agent and to treat various skin disorders, including wounds. AIMS OF THE STUDY: To investigated the influence of 5% Struthanthus vulgaris ointment during cutaneous wound healing in rats. MATERIALS AND METHODS: Twenty Wistar rats were used in each group according the daily treatment, S. vulgaris 5% ointment (SV 5%) and vehicle control groups. Four full thicknesses wounds were punched in back side skin of each animal, and five animals were sacrificed after 2, 7, 14 and 21 days after surgery for histological, immunological and biochemical analysis. RESULTS: A significant wound closured area in the S. vulgaris 5% group of about 38% and 35% as compared to 19% and 21% in the control group was observed after 2 and 5 days, respectively. Histological and biochemical analysis of the skin biopsies showed that S. vulgaris treated wounds exhibited increased granulation tissue and regulated the inflammatory response by modulating the release of pro and anti-inflammatory cytokines like IL-1α, TNF-α and IL-10, nitric oxide and, growth factors like TGF-ß. Moreover, S. vulgaris showed a marked and robust increase in the deposition and organization of collagen fibers in the wounds, and improve the quality of the scar tissue. CONCLUSIONS: Altogether these data revealed that S. vulgaris seems to prevent an over expression of inflammation and accelerates wound epithelialization and might be beneficial for treating healing disorders.
Asunto(s)
Antiinflamatorios/farmacología , Citocinas/metabolismo , Mediadores de Inflamación/metabolismo , Loranthaceae/química , Extractos Vegetales/farmacología , Piel/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Heridas Penetrantes/tratamiento farmacológico , Administración Cutánea , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/aislamiento & purificación , Biopsia , Cicatriz/metabolismo , Cicatriz/patología , Modelos Animales de Enfermedad , Colágenos Fibrilares/metabolismo , Tejido de Granulación/efectos de los fármacos , Tejido de Granulación/metabolismo , Tejido de Granulación/patología , Masculino , Pomadas , Fitoterapia , Extractos Vegetales/administración & dosificación , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta/química , Plantas Medicinales , Ratas Wistar , Repitelización/efectos de los fármacos , Piel/lesiones , Piel/metabolismo , Piel/patología , Factores de Tiempo , Heridas Penetrantes/metabolismo , Heridas Penetrantes/patologíaRESUMEN
In a previous study, we performed the chemical characterization of a polyvinyl alcohol (PVA) membrane supplemented with latex proteins (LP) displaying wound healing activity, and its efficacy as a delivery system was demonstrated. Here, we report on aspects of the mechanism underlying the performance of the PVA-latex protein biomembrane on wound healing. LP-PVA, but not PVA, induced more intense leukocyte (neutrophil) migration and mast cell degranulation during the inflammatory phase of the cicatricial process. Likewise, LP-PVA induced an increase in key markers and mediators of the inflammatory response (myeloperoxidase activity, nitric oxide, TNF, and IL-1ß). These results demonstrated that LP-PVA significantly accelerates the early phase of the inflammatory process by upregulating cytokine release. This remarkable effect improves the subsequent phases of the healing process. The polyvinyl alcohol membrane was fully absorbed as an inert support while LP was shown to be active. It is therefore concluded that the LP-PVA is a suitable bioresource for biomedical engineering.
Asunto(s)
Calotropis , Portadores de Fármacos , Látex/farmacología , Membranas Artificiales , Proteínas de Plantas/farmacología , Alcohol Polivinílico/química , Piel/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Heridas Penetrantes/tratamiento farmacológico , Administración Cutánea , Animales , Calotropis/química , Degranulación de la Célula/efectos de los fármacos , Modelos Animales de Enfermedad , Composición de Medicamentos , Mediadores de Inflamación/metabolismo , Interleucina-1beta/metabolismo , Látex/aislamiento & purificación , Activación de Macrófagos/efectos de los fármacos , Mastocitos/efectos de los fármacos , Mastocitos/metabolismo , Mastocitos/patología , Ratones , Infiltración Neutrófila/efectos de los fármacos , Óxido Nítrico/metabolismo , Peroxidasa/metabolismo , Fitoterapia , Proteínas de Plantas/aislamiento & purificación , Plantas Medicinales , Piel/lesiones , Piel/metabolismo , Piel/patología , Factores de Tiempo , Factor de Necrosis Tumoral alfa/metabolismo , Heridas Penetrantes/metabolismo , Heridas Penetrantes/patologíaRESUMEN
BACKGROUND: Estimation of the time period that precedes an injury is critical in forensic medicine. However, there is no reliable method that can be used to evaluate the oldness of a lesion. The aim of this work is to develop a fluorimetric method that can be used to follow the aging process of lesions by applying methyl-ALA (MAL) on wounds and by quantifying protoporphyrin IX (PPIX) fluorescence during the healing process. We also aim to understand the changes in PPIX fluorescence by establishing a correlation with histological evaluations during the healing process. METHODS: Standardized linear wounds were made on the dorsum of 72 mice, which were divided in control (MAL -) and experimental (MAL +) groups. In vivo fluorescence spectra (FS) were collected from normal and wound skin sites of control and experimental groups, corresponding to four groups of FS spectra: (a) FS of skin wound after MAL (+/+); (b) FS of normal skin after MAL (-/+); (c) FS of skin wound without MAL (+/-) and (d) FS of normal skin without MAL (-/-). Animals were monitored periodically for 3 months and euthanized. Tissue specimens were processed for histological analysis using design-based stereological methods. Serial cross-sections were analyzed to evaluate the organization of the dermis and epidermis, collagen deposition and cellular proliferation. RESULTS: FS of skin wound with MAL (+/+) showed an expressive intensity increase from the beginning of the experiment to the 34th day, with maximum fluorescence being observed on the ≈ 11 th day after wounding. There was preferential PPIX accumulation in healing sites as compared to adjacent normal skin (+/-) in the early stage of healing. Histological findings allowed correlation of the fluorescence increase mainly with cell proliferation. The drastic decrease in the FS intensity observed in the end of the healing process was correlated with the decrease in the proliferation rate as well as with the presence of new extracellular fibrous materials. CONCLUSIONS: In the mice wound-healing model tested here, it was possible to distinguish whether the injury was in early or advanced stages by using PPIX fluorescence induced by MAL. We conclude that this method is a promising approach to evaluate the age of skin wounding and we hope this work will stimulate human studies to allow this technique to become standardized in forensic medicine.
Asunto(s)
Envejecimiento/metabolismo , Ácidos Levulínicos , Protoporfirinas/análisis , Piel/química , Espectrometría de Fluorescencia/métodos , Cicatrización de Heridas/fisiología , Heridas Penetrantes/metabolismo , Envejecimiento/patología , Animales , Biomarcadores/metabolismo , Ácidos Levulínicos/análisis , Ratones , Ratones Desnudos , Fármacos Fotosensibilizantes , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Piel/lesiones , Piel/patología , Heridas Penetrantes/patologíaRESUMEN
Despite the large use of the Plantago major and Siparuna guianensis in traditional medicine, there are no studies demonstrating the effectiveness from extracts of these plants in the healing process by the present methodology. This study reported the effects and toxicity of the P. major and S. guianensis extracts in the wound healing compared with a commercial product used in Brazil by macroscopic and microscopic analysis. Following injury in cervical dorsal area of the mice, the extract from P. major and S. guianensis and ointment was applied after an injury in cervical dorsal area of the mice. Wound healing rates were calculated at 4, 9, 15 and 21 d after the wounding, and tissues were obtained on the ninth day for histological analysis. Moreover, mutagenic assay of extracts was performed. Mutagenicity studies carried out with plant extracts showed not mutagenic with or without metabolic activations. Reduction of the wound area occurred earlier in mice treated with P. major and control treatment. On the 15th day, the complete wound closure occurred in P. major-treated wounds. Throughout ointment and S. guianensis treatment it was not observed the wound closured. Microscopic analyses of the wound, on the ninth day, showed the more efficient formation of the neoepithelium and skin appendages in animals treated with S. guianensis and P. major, while ointment treatment presented no re-epithelialization and absent skin appendages in wound. Thus, P. major extract showed good effects on wound healing processes rendering it a promising candidate for the treatment of wounds what also justified its traditional usage in wound treatment.
Asunto(s)
Extractos Vegetales , Plantago/química , Salmonella typhimurium/crecimiento & desarrollo , Salmonella typhimurium/genética , Cicatrización de Heridas/efectos de los fármacos , Heridas Penetrantes/tratamiento farmacológico , Animales , Masculino , Ratones , Pruebas de Mutagenicidad/métodos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Heridas Penetrantes/genética , Heridas Penetrantes/metabolismo , Heridas Penetrantes/patologíaRESUMEN
OBJECTIVE: The aim of the present investigation was to evaluate transforming growth factor ß (TGF-ß) expression on cutaneous wounds in rodents treated or not treated with LED light. BACKGROUND: TGF-ß is a multifunctional cytokine that presents a central action during tissue repair. Although several studies both in vitro and in vivo have shown that LED phototherapy influences tissue repair, a full understanding of the mechanisms involved in its usage, such as in the modulation of some growth factors, remains unclear. MATERIALS AND METHODS: Under general anesthesia, 24 young adult male Wistar rats weighing 200-250 g had one excisional wound created on the dorsum of each, and were randomly distributed into two groups: G0 (Control) and G1 (LED, λ700 ± 20 nm, 16 mW, SAEF = 5 J/cm(2), Illuminated Area = 2 cm(2), 8 mWcm(2), 626 s) Each group was subdivided into three subgroups according to the animal death timing (2, 4, and 6 days). LED phototherapy started immediately after surgery and was repeated every other day during the experimental time. Following animal death, specimens were removed, routinely processed to wax, cut and immunomarked with polyclonal anti-TGF-ß, and underwent histological analysis by light microscopy. The mean area of expression of each group was calculated. The data were statistically analyzed using ANOVA and Tukey's test. RESULTS: The area of the expression of TGF-ß on LED-irradiated animals was significantly smaller than on controls at day 2 (p = 0.013). No significant difference was found at later times. It is concluded that the use of LED light, at these specific parameters, caused an inhibition of the expression of TGF-ß at an early stage of the healing process.
Asunto(s)
Fototerapia , Factor de Crecimiento Transformador beta/metabolismo , Heridas Penetrantes/metabolismo , Heridas Penetrantes/terapia , Animales , Modelos Animales de Enfermedad , Tejido de Granulación/metabolismo , Masculino , Ratas , Ratas Wistar , Cicatrización de Heridas , Heridas Penetrantes/patologíaRESUMEN
Growth factors have proved to be an effective therapeutic strategy. However, some controversies have arisen concerning their efficacy in topical wound treatments. Stabilization of epidermal growth factors at the wound site and long-lasting receptor occupancy are important factors for wound repair. This study evaluated the cumulative profiles of two jellies containing 10 or 20 microg of 125I-rhEGF per gram of jelly, in a rat full-thickness skin lesion model. The prolonged time-courses at the wound sites for both strengths compared with saline solutions previously evaluated using a similar skin lesion model are reported. It seems that these two topical formulations that provide more sustained amounts of 125I-rhEGF over the period of sampling, would probably achieve the required wound healing response in terms of cell proliferation, collagen deposition and protein synthesis. Further studies need to be developed in order to elucidate whether such an in vivo disposition pattern is consistent with an earlier and stronger promotion of wound healing events.
Asunto(s)
Factor de Crecimiento Epidérmico/administración & dosificación , Factor de Crecimiento Epidérmico/farmacocinética , Heridas Penetrantes/tratamiento farmacológico , Heridas Penetrantes/metabolismo , Administración Tópica , Animales , Química Farmacéutica , Factor de Crecimiento Epidérmico/uso terapéutico , Geles , Humanos , Radioisótopos de Yodo/administración & dosificación , Radioisótopos de Yodo/farmacocinética , Masculino , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/uso terapéuticoRESUMEN
Injury triggers a series of physiological events at the wound site. These include an inflammatory response that is established shortly after the injury, which is then followed by an intense formation of tissue over a period of days. Poly- and monounsaturated fatty acids exert major functions on the inflammatory responses, either in the form of phospholipids anchored in the cell membrane or as soluble lipoic mediators. We present evidence that linolenic (n-3), linoleic (n-6), and oleic (n-9) fatty acids can modulate the closure of surgically induced skin wounds. We found that n-9 fatty acids induced faster wound closure when compared to n-3, n-6, and control. In addition, n-9 fatty acids strongly inhibited the production of nitric oxide at the wound site. A mild improvement on wound closure was observed in the n-6 fatty acid-treated animals concurrent with a peak in nitric oxide production at 48 hours postsurgery. N-3 fatty acid treatment significantly delayed wound closure. Furthermore, we showed that n-3 fatty acid induced a peak in nitric oxide at 3 hours postsurgery and an intense deposition of extracellular matrix after 5 days of treatment. Thus, our results suggest a relevant role and potential therapeutic implication for fatty acids on skin wound healing.