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Cost-effective strategies for the treatment of chronic wounds must be developed. The green synthesis of gold nanoparticles (GNPs) it is possible to guarantee a lower toxicity in biological tissues and greater safety of applicability, in addition to adding the effects of nanoparticles (NPs) to those of extracts. The objective of this study was to evaluate the effects of treatment with biosynthesized GNPs in a chronic wound model. Wistar rats were distributed into 7 groups: Acute Wound (AW); Chronic wound (CW); CW + GNPs-Açaí; CW + GNPs-DB; CW + AV-GNPs; CW + SafGel®; CW + 660 nm laser. The chronic injury model was induced with topically applied Resiquimod for 6 days. Treatments were then initated on the fourteenth day after the last application of Resiquimod and carried out daily for ten days. The proposed therapies with GNPs were able to significantly reduce the inflammatory score and increase the rate of wound contraction. In histology, there was a reduction in the inflammatory infiltrate and increased gene expression of fibronectin and type III collagen, mainly in the CW + AV-GNPs group. The therapies were able to reduce pro-inflammatory cytokines, increase anti-inflammatory cytokines, and reduce oxidative stress. The results demonstrated that the effects of GNPs appear to complement those of the extracts, thereby enhancing the tissue repair process.

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This study aimed to investigate the effect of intranasal treatment of gold nanoparticles (GNPs) and Curcumin (Cur) on the lipopolysaccharide (LPS)-induced acute pulmonary inflammatory response. A single intraperitoneal injection of LPS (0.5 mg/Kg) was performed, and the animals in the Sham group were injected with 0.9% saline. Treatment was daily intranasally with GNPs (2.5 mg/L), Cur (10 mg/kg) and GNP-Cur started 12 h after LPS administration and ended on the seventh day. The results show that the treatment performed with GNP-Cur was the most effective to attenuate the action of pro-inflammatory cytokines, and a lower leukocyte count in the bronchoalveolar lavage, in addition to positively regulating anti-inflammatory cytokines in relation to other groups. As a result, it promoted an oxirreductive balanced environment in the lung tissue, providing a histological outcome with a reduction in inflammatory cells and greater alveolar area. The group treated with GNPs-Cur was superior to the other groups, with better anti-inflammatory activity and reduced oxidative stress, resulting in less morphological damage to lung tissue. In conclusion, the use of reduced GNPs with curcumin demonstrates promising effects in the control of the acute inflammatory response, helping to protect the lung tissue at the biochemical and morphological levels.

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A perfect graft for wound care must be readily available without affecting the immune response, covering and protecting the wound bed. Considering previous studies have already established the use of hyaluronic acid (HA) for the treatment of wounds but the data presented on the amniotic membrane (AM) and its promising effects on healing still requires further investigation, this study aimed to evaluate the effects of the application of a decellularized amniotic membrane solubilized with hyaluronic acid on the healing process of cutaneous wounds on the 7th and 14th day, to evaluate the evolution of the wound and the inflammatory phases in these two times. Cutaneous lesions were excised from the dorsal region and 96 Wistar rats were divided into four groups: I-Excisional wound (EW); II-EW + AM; III-EW + HA; IV-EW + AM + HA. The present study demonstrated that the proposed combined therapy favors the tissue repair process of the epithelial lesion. Results showed a reduction in pro-inflammatory cytokines, an increase in anti-inflammatory cytokines, an increase in TGF-ß, and attenuation of oxidative stress, reducing the acute inflammatory response and promoting the beginning of tissue repair. We concluded that the proposed therapies accelerated the inflammatory process with anticipation of the repair phase.

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Objectives: This article aimed to investigate the effects of the association between photobiomodulation and hyaluronic acid incorporated in lipid nanoparticles in an epithelial lesion model in inflammatory parameters and oxidative stress. Methods: Eighty Wistar rats were randomly assigned to the following groups: epithelial lesion group (EL); EL+PBM; EL+HA; EL+SLNs; EL+SLNs-HA; EL+PBM+HA; EL+PBM+SLNs; EL+PBM+SLNs-HA. The animals were anesthetized with 4% isofluorane after shaving and induced to an epithelial lesion. Topical treatment with a gel containing HA (0.9%) and/or SLNs (10 mg/mL) and with laser irradiation occurred daily for 1 week. Results: The results showed an increase in wound contraction on the seventh day in the LE + LBM + AH-NPL group, a reduction in pro-inflammatory cytokines (IL-6, IL-1ß, and TNF-α), an increase in anti-inflammatory cytokines (IL- 4 and IL-10) and TGF-ß. The levels of pro-inflammatory cytokine IL-4 and TGF-ß also showed an increase in the LE + NPL-AH, LE + FBM + AH, LE + FBM + NPL and LE + FBM + NPL-AH groups. Regarding oxidative stress parameters, the levels of DCF and nitrite decreased in the combined therapy group when compared to the control group, as well as oxidative damage (carbonyl and sulfhydryl). In the antioxidant defense, there was an increase in GSH and SOD in the combination therapy group. Histological analysis showed a reduction in inflammatory infiltrate in the combination therapy group. The number of fibroblasts and the compaction of collagen fibers did not obtain significant responses. Conclusions: Results analyzed together showed that the combined therapy favored the repair process, and that studies can be carried out to enhance the histological analysis therapy favored the tissue repair process and that studies can be carried out to enhance the histological analysis.

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Photobiomodulation-PBM and Photodynamic Therapy-PDT have been used to induce healing. However, the effects of these therapies on skin-lesions induced by electrocautery are unknown, aiming at more favorable clinical and esthetic results. Electrocauterization was done in 78-female Wistar-rats using a system that includes an electrocautery and red-LED. The groups were: No injury, Injury, Injury + ALA (topical 5-aminolevulinic acid application), Injury + LED and Injury + ALA + LED (topical ALA application followed by photoactivation with LED). After 2nd, 7th and 14th days post-injury, immuno-histomorphometric analyses (inflammatory infiltrate, blood vessels, fibroblasts, eschar/epidermal thickness, IL-10 and VEGF) and biochemical assays of MPO (neutrophil), NAG (macrophage), nitrite, DCF (H2 O2 ), carbonyl (membrane's damage), sulfhydryl (membrane's integrity), SOD, GSH, hydroxyproline and re-epithelialization area were performed. The Injury + LED and Injury + ALA + LED groups controlled inflammation and oxidative stress, favoring angiogenesis, fibroblasts proliferation and collagen formation. Therefore, the PBM or PDT was effective in tissue formation with thinner eschar and epidermis, resulting in less scarring after electrocauterization.

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In this study, we performed two experiments. In the first experiment, the objective was to link gold nanoparticles (GNPs) with sodium diclofenac and/or soy lecithin and to determine their concentration in tissues and their toxicity using hepatic and renal analyzes in mice to evaluate their safety as therapeutic agents in the subsequent treatment of obesity. In the second experiment, we evaluated the effect of GNPs on inflammatory and biochemical parameters in obese mice. In the first experiment, we synthesized and characterized 18 nm GNPs that were administered intraperitoneally in isolation or in association with sodium diclofenac and/or soy lecithin in mice once daily for 1 or 14 days. Twenty-four hours after the single or final administration, the animals were euthanized, following which the tissues were removed for evaluating the concentration of GNPs, and serum samples were collected for hepatic and renal analysis. Hepatic damage was evaluated based on the levels of alanine aminotransferase (ALT), whereas renal damage was evaluated based on creatinine levels. A higher concentration of GNPs was detected in the tissues upon administration for 14 days, and there were no signs of hepatic or renal damage. In the second experiment, the mice were used as animal models of obesity and were fed a high-fat diet (obese group) and control diet (control group). After eight weeks of high-fat diet administration, the mice were treated with saline or with GNPs (average size of 18 nm) at a concentration of 70 mg/L (70 mg/kg) once a day, for 14 days, for 10 weeks. Body weight and food intake were measured frequently. After the experiment ended, the animals were euthanized, serum samples were collected for glucose and lipid profile analysis, the mesenteric fat content was weighed, and the brains were removed for inflammatory and biochemical analysis. In obese mice, although GNP administration did not reduce body and mesenteric fat weight, it reduced food intake. The glucose levels were reversed upon administration of GNPs, whereas the lipid profile was not altered in any of the groups. GNPs exerted a beneficial effect on inflammation and oxidative stress parameters, without reverting mitochondrial dysfunction. Our results indicate that the intraperitoneal administration of GNPs for 14 days results in a significant GNP concentration in adipose tissues, which could be an interesting finding for the treatment of inflammation associated with obesity. Based on the efficacy of GNPs in reducing dietary intake, inflammation, and oxidative stress, they can be considered potential alternative agents for the treatment of obesity.

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Percutaneous collagen induction (PCI) is an alternative treatment for skin dysfunctions, it aims to stimulate collagen production by encouraging normal wound healing that occurs after any trauma by inducing microlesions; also it may be potentiated with the association with drugs such as hyaluronic acid (HA). Our objective was to evaluate the effects of PCI associated with hyaluronic acid (0.9%) on inflammatory process, oxidative stress, and collagen production in rat epidermis. For the study, 36 adult Wistar rats were randomly divided into 6 groups (n = 6): Control; PCI 0.5; PCI 1.0; HA; PCI 0.5 + HA; and PCI 1.0 + HA. The animals were anesthetized, trichotomized, and the application of therapies was performed once; After 7 days, the animals were euthanized for removal of the skin region. Levels of pro-inflammatory (IL1, IL6, TNFα), anti-inflammatory (IL4 and IL10) cytokines and growth factors (FGF, TGFß) were evaluated, besides oxidative stress parameters and histological analysis. In combination groups, there is a decrease in TNFα compared with the control and PCI groups in contrast to a significant increase in anti-inflammatory cytokines and growth factors. Oxidant and oxidative damage levels showed a significant decrease in PCI + HA groups in relation to PCI groups while antioxidant defense increased in PCI + HA groups compared with the control group. The number of fibroblasts was increased in the PCI 1.0 group in relation to the control, HA, and PCI 0.5. The number of blood vessels and collagen area was increased in groups PCI and PCI + HA compared with the HA group. We conclude that the combination of PCI with HA is able to accelerate the acute inflammatory process, reducing its deleterious effects and anticipating the chronic response, contributing to tissue repair.

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The use of nanotechnology for administering drugs is a recent development that presents promising results. Therapeutic Pulsed Ultrasound (TPU) is one such therapeutic option and is widely used for treating soft tissue lesions. Thus, the objective of this study was to investigate the therapeutic effect of phonophoresis using diclofenac (DC) linked to gold nanoparticles (GNPs) in the skeletal muscle of rats used as a model of traumatic muscular injury. Wistar rats were divided into eight groups (N = 10): Sham, Muscle injury (MI), MI + TPU, MI + DC, MI + GNPs, MI + TPU + DC, MI + TPU + GNPs, and MI + TPU + DC-GNPs. The traumatic injury was performed in the gastrocnemius with a single direct traumatic impact via an injuring press. The animals received daily treatment for 5 consecutive days with TPU and gel with DC and/or GNPs. Two hours after the last treatment session, animals were euthanized and the gastrocnemius muscle surgically removed for histological and biochemical analysis. The groups exposed to some therapies (MI + TPU + DC, MI + TPU + GNPs and MI + TPU + DC-GNPs) showed reduced levels of pro-inflammatory cytokines, whereas an increase in anti-inflammatory cytokine levels was observed in the group exposed to all therapies combined (MI + TPU + DC-GNPs). Reactive species production and protein damage resulting from oxidative damage was lower for the group exposed to all tested therapies had lower production. Lower protein damage was also observed in the TPU + GNPs group. The group that underwent all tested therapies combined showed a significant increase in antioxidants compared to the MI group. During histological analysis, the MI group showed large amounts of cell infiltration and centralized nuclei, whereas the MI + TPU + DC-GNPs group showed structural improvements. Pain levels in the MI + TPU + DC-GNPs group were lower than those of the MI group. We believe that the association of TPU with DC linked to GNPs decreases the inflammation caused by traumatic muscle injury and accelerates tissue repair.

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Duchenne muscular dystrophy (DMD) is an X-linked recessive hereditary myopathy characterised by progressive muscle degeneration in male children. As a consequence of DMD, increased inflammation and oxidative stress occur in muscle tissue along with morphological changes. Several studies have reported anti-inflammatory and antioxidant effects of gold nanoparticles (GNP) in muscle injury models. The objective of this study was to evaluate these effects along with the impacts of the disease on histopathological changes following chronic administration of GNP to Mdx mice. Two-month-old Mdx mice were separated into five groups of eight individuals each, as follows: wild-type (WT), Mdx-modified without treatment, Mdx + 2.5 mg/kg GNP, Mdx + 7.0 mg/kg GNP and Mdx + 21 mg/kg GNP. GNP with a mean diameter of 20 nm were injected subcutaneously at concentrations of 2.5, 7.0 and 21 mg/kg. Treatments continued for 30 d with injections administered at 48-h intervals. Twenty-four hours after the last injection, the animals were killed and the central region of the gastrocnemius muscle was surgically removed. Chronic administration of GNP reduced inflammation in the gastrocnemius muscle of Mdx mice and reduced morphological alterations due to inflammatory responses to muscular dystrophy. In addition, GNP also demonstrated antioxidant potential by reducing the production of reactive oxygen and nitrogen species, reducing oxidative damage and improving antioxidant activity.

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The repair process consists of molecular and cellular events that can be accelerated by specific therapies. Considering this, the objective of this study was to evaluate the effects of ibuprofen phonophoresis associated with gold nanoparticles in the animal model of traumatic muscle injury. Was used 80 male wistar rats divided into eight groups: Sham; Muscle injury (MI); MI + therapeutic pulsed ultrasound (TPU); MI + Ibuprofen (IBU); MI + GNPs; MI + TPU+ IBU; MI + TPU + GNPs and MI + TPU + IBU + GNPs. The lesion in the gastrocnemius was performed by a single direct trauma impact on the injured press. The animals were treated with pulsed ultrasound and the gel with gold nanoparticles and/or ibuprofen. The treatment was applied daily for 5 days and the first session was 12 h after the muscle injury. The gastrocnemius muscle was surgically removed for analyzes biochemical, molecular and histological. In the analyzes only the MI + TPU + IBU + GNPs group showed a reduction in TNF-a and IL-1 levels, with a concomitant increase in the levels of anti-inflammatory cytokines. In the analysis of oxidative stress, only the MI + TPU + IBU + GNPs group presented a reversal of the condition when compared to the MI group. In the histological analysis, the MI group presented a large cell infiltrate and a centralized nucleus and only the MI + TPU + IBU + GNPs group showed a structural improvement, also in the pain results the MI + TPU + IBU + GNPs showed a significant difference in comparison to the MI group (p<0.01). We believe that the effects of phonophoresis with anti-inflammatory drugs associated with gold nanoparticles may potentiate the reduction of the inflammatory response and regulate the cellular redox state.

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