Effect of photobiomodulation therapy on the proliferation phase and wound healing in rats fed with an experimental hypoproteic diet.

Photobiomodulation therapy (PBMT) has been indicated for enforcement on healing skin wounds. This study evaluated the effects of PBMT on the healing of skin wounds during the proliferation phase in rats with a hypoproteic diet. Rats were randomized to one of the following groups (n = 10 per group): (i) injured normoproteic (25% protein) not subjected to PBMT; (ii) injured normoproteic who received PBMT; (iii) injured hypoproteic (8% protein) not subjected to PBMT; and (iv) injured hypoproteic who received PBMT. Rats were submitted to skin wounds and then treated with PBMT (low-level laser therapy: 660 nm, 50 mW, 1.07 W/cm2, 0.028 cm2, 72 J/cm2, 2 J). Analyses were performed at 7 and 14 days of follow-up: semi-quantitative histopathologic analysis, collagen type I and III expressions, immunohistochemical marking for matrix metalloproteinases-3 (MMP-3) and (matrix metalloproteinases-9) MMP-9, and mechanical resistance test. There were significant differences between the normoproteic groups and their respective treated groups (p < 0.05), as well as to treated and untreated hypoproteic groups in histopathologic analysis semi-quantitatively and immunohistochemistry for MMP-3 and 9, in which PBMT was able to decrease immunostaining. Moreover, there was a decrease in collagen deposition with the statistical difference (p < 0.05) for both collagen types III and I. In conclusion, PBMT application was proved effective in the treatment of cutaneous wounds in rats submitted to a hypoproteic diet. These alterations were more salient in the proliferation stage with the reduction of metalloproteinases providing better mechanical resistance of the injured area in the remodeling phase with an intensification of type I collagen.

Parameters and Effects of Photobiomodulation in Plantar Fasciitis: A Meta-Analysis and Systematic Review.

Objective: This systematic review and meta-analysis updated the effects of photobiomodulation therapy (PBMT) on pain, the Foot Function Index (FFI), and the effects on fascial thickness in adults with acute or chronic plantar fasciitis (PF). Methods: A systematic literature search was conducted in the PubMed (Public/Publisher MEDLINE), EMBASE (Excerpta Medica Database), and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases. Two researchers independently screened titles and abstracts of the retrieved studies for eligibility. A random-effects model was used for this meta-analysis. Subgroup meta-analyses were conducted to evaluate the influence of PBMT in pain and foot function under investigation and the study design on the overall weighted mean effect size. Results: From a total of 3865 studies, 7 randomized controlled trials were selected after final review and 4 were selected for meta-analysis. There was a significant difference between PBMT and control for Visual Analog Scale (Chi2 = 29.30; p < 0.00001) with an I2 value of 90% in favor of PBMT versus the control. The overall effect of PBMT was statistically significant (p < 0.02) with PBMT favoring for thickness of the plantar fascia reduction. FFI between PBMT and control group [Chi2 -83.46, df = 1 (p < 0.00001)]; I2 = 99% in favor of the PBMT. Conclusions: This meta-analysis presents evidence that PBMT is an effective treatment modality to reduce pain and improvement of foot function in patients with chronic PF, however, a broad discrepancy was found in the PBMT dosimetry. The ideal treatment parameters for PF need to be elucidated.

Effects and parameters of the photobiomodulation in experimental models of third-degree burn: systematic review.

This systematic review was performed to identify the role of photobiomodulation therapy in experimental models of third-degree burns used to induce oxidative stress. EMBASE, PubMed, and CINAHL databases were searched for studies published between January 2003 and January 2018 on the topics of photobiomodulation therapy and third-degree burns. Any study that assessed the effects of photobiomodulation therapy in animal models of third-degree burns was included in the analysis. A total of 17 studies were selected from 1182 original articles targeted on photobiomodulation therapy and third-degree burns. Two independent raters with a structured tool for rating the research quality critically assessed the articles. Although the small number of studies limits the conclusions, the current literature research indicates that photobiomodulation therapy can be an effective short-term approach to accelerate the healing process of third-degree burns, to increase and modulate the inflammatory process, to accelerate the proliferation of fibroblasts, and to enhance the quality of the collagen network. However, differences still exist in the terminology used to describe the parameters and the dose of photobiomodulation therapy.

Photobiomodulation therapy on bothrops snake venom-induced local pathological effects: A systematic review.

Bothrops snakebite treatment is antivenom therapy, which is ineffective in neutralizing the severe local effects caused by these envenomations. There are evidence that photobiomodulation therapy (PBMT) has emerged as a promising tool to counteract the venom-induced local effects. The purpose was to write a narrative review of the literature about PBMT as a treatment for Bothrops snakebites. We reviewed articles indexed in PubMed, SCOPUS and Scientif Direct database with filter application. Included studies had to investigate local effects induced by Bothrops snake venom in any animal model using any type of photobiomodulation irradiation and at least one quantitative measure of local effects of Bothrops envenomation. Sixteen studies were selected from 54 original articles targeted PBMT (low-level laser or light emitting diode) as a complementary tool for local effects treatment induced by snakebites, and all its assessments. Articles were critically assessed by two independent raters with a structured tool for rating the research quality. PBMT demonstrate to be a promising tool for local treatment effects caused by snakebite by reducing local edema, hyperalgesia, leukocyte influx and myonecrosis and accelerating tissue regeneration related to myotoxicity. However, the mechanism is not well understood and additional studies are needed.

Effect of photobiomodulation therapy on oxidative stress markers of gastrocnemius muscle of diabetic rats subjected to high-intensity exercise.

This study aimed to determine whether photobiomodulation therapy (PBMT) in diabetic rats subjected to high-intensity exercise interferes with the expression of the oxidative stress marker in the gastrocnemius muscle. Twenty-four male Wistar rats were included in this study comprising 16 diabetic and eight control rats. The animals were allocated into three groups-control, diabetic fatigue, and diabetic PBMT fatigue groups. Diabetes was induced via the intraperitoneal administration of streptozotocin (50 mg/kg). We subsequently assessed blood lactate levels and PBMT. The animals of the diabetic fatigue group PBMT were irradiated before the beginning of the exercises, with dose of 4 J and 808 nm, were submitted to treadmill running with speed and gradual slope until exhaustion, as observed by the maximum volume of oxygen and lactate level. The animals were euthanized and muscle tissue was removed for analysis of SOD markers, including catalase (CAT), glutathione peroxidase (GPx), and 2-thiobarbituric acid (TBARS) reactive substances. CAT, SOD, and GPx activities were significantly higher in the diabetic PBMT fatigue group (p < 0.05) than in the diabetic fatigue group. Outcomes for the diabetic PBMT fatigue group were similar to those of the control group (p > 0.05), while their antioxidant enzymes were significantly higher than those of the diabetic fatigue group. PBMT mitigated the TBARS concentration (p > 0.05). PBMT may reduce oxidative stress and be an alternative method of maintaining physical fitness when subjects are unable to perform exercise. However, this finding requires further testing in clinical studies.

Can photobiomodulation associated with implantation of mesenchymal adipose-derived stem cells attenuate the expression of MMPs and decrease degradation of type II collagen in an experimental model of osteoarthritis?

This study aimed to determine whether photobiomodulation therapy (PBMT) could improve the bioavailability and chondroprotective benefits of mesenchymal stem cells injected into the knees of rats used as an experimental model of osteoarthritis (OA) as well as reduce the expression of matrix metalloproteinases (MMPs) and degradation of type II collagen (COL2-1) in the cartilage. Adipose-derived stem/stromal cells (ADSCs) were collected from three male Fischer 344 rats and characterized by flow cytometry. Fifty female Fischer 344 rats were distributed into five groups of 10 animals each. These groups were as follows: control, OA, OA PBMT, OA ADSC, and OA ADSC PBMT. OA was induced in the animals using a 4% papain solution. Animals from the OA ADSC and OA ADSC PBMT groups received an intra-articular injection of 10 × 106 ADSCs and were treated with PBMT by irradiation (wavelength: 808 nm, power: 50 mW, energy: 42 J, energy density: 71.2 J/cm2, spot size: 0.028). Euthanasia was performed 7 days after the first treatment. The use of PBMT alone and the injection of ADSCs resulted in downregulation of pro-inflammatory cytokines and MPs in cartilage compared to the OA group. PBMT and ADSCs caused upregulation of tissue inhibitors of MPs 1 and 2 and mRNA and protein expression of COL2-1 in cartilage compared to the OA group. The intra-articular injection of ADSCs and PBMT prevented joint degeneration resulting from COL2-1 degradation and modulated inflammation by downregulating cytokines and MMPs in the OA group.

Effects of Photobiomodulation Therapy on Oxidative Stress in Muscle Injury Animal Models: A Systematic Review.

This systematic review was performed to identify the role of photobiomodulation therapy on experimental muscle injury models linked to induce oxidative stress. EMBASE, PubMed, and CINAHL were searched for studies published from January 2006 to January 2016 in the areas of laser and oxidative stress. Any animal model using photobiomodulation therapy to modulate oxidative stress was included in analysis. Eight studies were selected from 68 original articles targeted on laser irradiation and oxidative stress. Articles were critically assessed by two independent raters with a structured tool for rating the research quality. Although the small number of studies limits conclusions, the current literature indicates that photobiomodulation therapy can be an effective short-term approach to reduce oxidative stress markers (e.g., thiobarbituric acid-reactive) and to increase antioxidant substances (e.g., catalase, glutathione peroxidase, and superoxide dismutase). However, there is a nonuniformity in the terminology used to describe the parameters and dose for low-level laser treatment.

Photobiomodulation therapy action in wound repair skin induced in aged rats old: time course of biomarkers inflammatory and repair.

Previous studies have discussed an inverse correlation between age and wound healing, because it relates to the association of aging with a gradual decrease in healing capacity. Treatment with photobiomodulation therapy (PBMT) improves wound healing by inducing increases in mitotic activity, numbers of fibroblasts, collagen synthesis, and neovascularization. Therefore, this study aimed to evaluate the effects of PBMT in cutaneous wound healing in aged rats. A punch biopsy of 8 mm in diameter was performed to produce a skin wound. The study included 45 male rats, of which 15 were young (30 days) and 30 were elderly (500 days). The 45 animals were distributed into 3 experimental groups, which were subjected to skin wounds and 1 aged group received PBMT, with a 30-mW laser beam (power density of 1.07 W/cm2), beam area of 0.028 cm2, and λ660 nm produced through active phosphide Gallium-Aluminum-Indio (InGaAIP). The PBMT application took the form of a single-point transcutaneous method, with a total energy of 2 joules per wound site, energy density of 72 J/cm2, and time of 1 min and 7 s. Analysis was performed to verify the effect of PBMT on the quantity of collagen I and III, metalloproteinase 3 and 9 (MMP-3 and MMP-9), tissue inhibitor of metalloproteinase-2 (TIMP-2) and of vascular endothelial growth factor (VEGF) at the wound site by immunohistochemistry, cytokine-induced neutrophil chemoattractant (CINC)-1, by enzyme-linked immunosorbent assay (ELISA) and interleukin (IL)-6 real-time polymerase chain reaction (RT-PCR). That we conclude LLLT is effective in the modulation of inflammatory mediators IL-6, CINC-1, VEGF, MMP-3, MMP-9 and TIMP-2 as well as increased collagen production in aged animals during different phases of the tissue regeneration process. However, the effects of PBMT obtained in the aged animals (aged LLLT group) suggest that new dosimetries should be tested to achieve better results.

Photobiomodulation therapy associated with treadmill training in the oxidative stress in a collagen-induced arthritis model.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by chronic and systemic inflammation, which leads to the destruction of the cartilage and bone and affects tissues in multiple joints. Oxidative stress has been implicated with regards to involvement in various disease conditions, such as diabetes mellitus and neurodegenerative, respiratory, cardiovascular, and RA diseases. In vivo experimental studies using photobiomodulation therapy (PBMT) have shown positive effects in reducing lipid peroxidation and in increasing antioxidant activity. The regular practice of physical exercise has also been reported to be a beneficial treatment capable of reducing oxidative damage. Thus, the aim of this study was to analyze the effects of photobiomodulation therapy at 2- and 4-J doses associated with physical exercise on oxidative stress in an experimental model of RA in protein expression involving superoxide dismutase (SOD), glutathione peroxidase (GPX), and/or catalase (CAT) on thiobarbituric acid reactive substances (TBARS). In this study, 24 male Wistar rats divided into four groups were submitted to an RA model (i.e., collagen-induced arthritis, CIA), with the first immunization performed at the base of the tail on days 0 and 7 were included. After 28 days, a third intraarticular dose was administered in both knees of the animals. After the last induction, PBMT was started immediately, transcutaneously at two points (i.e., the medial and lateral), with a total of 15 applications. Treadmill exercise was also started the day after the last induction, and lasted for 5 weeks. With respect to results, we obtained the decreases in the lipid peroxidation and the increases of the antioxidant activities of SOD, GPX and CAT, with physical exercise associated to PBMT in doses of 2 and 4 J. In conclusion, physical exercise associated with PBMT decreases lipid peroxidation and increases antioxidant activity.

Effect of low-level laser therapy on metalloproteinase MMP-2 and MMP-9 production and percentage of collagen types I and III in a papain cartilage injury model.

Osteoarthritis (OA) resulting from injury or disease is associated with increased levels of several matrix metalloproteinases (MMPs), which degrade all components of the complex extracellular matrix in the cartilage. The objective of this study is to investigate the effect of low-level laser therapy (LLLT) on papain-induced joint damage in rats by histopathology and analysis of metalloproteinase 2 and 9 production. Sixty male Wistar rats were randomly distributed into four groups of 15 animals: (1) non-injury negative control, (2) injury positive control, (3) treated with LLLT at 50 mW, and (4) treated with LLLT at 100 mW. OA was induced in animals using papain (4 % solution) followed by treatment with LLLT. After 7, 14, and 21 days, the animals were euthanized. The articular lavage was collected and centrifuged; then, the supernatant was stored prior to protein analysis by western blot. The material was stained with hematoxylin and eosin for histopathological analysis, and Picrosirius Red was used to estimate the percentage of collagen fibers. To determine normal distribution, ANOVA and Tukey's post hoc test were used for comparison between and within each group at each time period. All data are expressed as mean and standard deviation values, with the null hypothesis considered as p < 0.05. Both laser groups (50 and 100 mW) were effective in tissue repair, decreasing collagen type III expression and increasing type I expression in all experimental periods; however, LLLT at 50 mW reduced metalloproteinase 9 more than at 100 mW in 21 days. LLLT at 50 mW was more efficient in the modulation of matrix MMPs and tissue repair.

Comparative analysis of two low-level laser doses on the expression of inflammatory mediators and on neutrophils and macrophages in acute joint inflammation.

Synovial membrane inflammation plays an important role in osteoarthritis (OA) pathophysiology. The synovial tissue of patients with initial OA is characterized by mononuclear cell infiltration and the production of pro-inflammatory cytokines and other mediators of joint injury. The study aims to evaluate the effect of low-level laser therapy (LLLT) at doses of 2 and 4 J on joint inflammation in rats induced by papain through histopathological analysis, differential counts of inflammatory cells; gene expression of IL-1ß, IL-6, and IL-10; and TNF-α protein expression. Male Wistar rats (20) were randomly divided (5 animals each) into a negative control group, an inflammation injury positive control group, a 2-J LLLT group subjected to injury and treated with 2 J of LLLT, and a 4-J LLLT group subjected to injury and treated with 4 J of LLLT. The animals were subjected to joint inflammation (4 % papain solution) and treated with LLLT. On the day of euthanasia, articular lavage was collected and centrifuged. The supernatant was analyzed for TNF-α protein expression by ELISA and IL-1ß, IL-6, and IL-10 mRNA by RT-PCR. The joint tissue was also examined histologically. ANOVA with Tukey's post hoc test was used for comparisons. All data were expressed as means ± S.D. (p < 0.05). Both laser modalities were efficient in reducing cellular inflammation and decreasing the expression of IL-1ß and IL-6. However, the 2-J treatment led to more reduction in TNF-α than the 4-J treatment. A single application of LLLT with 2 J was more efficient in modulating inflammatory mediators and inflammatory cells.

Effect of low-level laser therapy on the expression of inflammatory mediators and on neutrophils and macrophages in acute joint inflammation.

INTRODUCTION: Inflammation of the synovial membrane plays an important role in the pathophysiology of osteoarthritis (OA). The synovial tissue of patients with initial OA is characterized by infiltration of mononuclear cells and production of proinflammatory cytokines and other mediators of joint injury. The objective was to evaluate the effect of low-level laser therapy (LLLT) operating at 50 mW and 100 mW on joint inflammation in rats induced by papain, through histopathological analysis, differential counts of inflammatory cells (macrophages and neutrophils), as well as gene expression of interleukin 1-beta and 6 (IL-1ß and IL-6), and protein expression of tumor necrosis factor alpha (TNFα). METHODS: Male Wistar rats (n = 60) were randomly divided into four groups of 15 animals, namely: a negative control group; an inflammation injury positive control group; a 50 mW LLLT group, subjected to injury and treated with 50 mW LLLT; and a 100 mW LLLT group, subjected to injury and treated with 100 mW LLLT. The animals were subject to joint inflammation (papain solution, 4%) and then treated with LLLT (808 nm, 4 J, 142.4 J/cm(2), spot size 0.028 for both groups). On the day of euthanasia, articular lavage was collected and immediately centrifuged; the supernatant was saved for analysis of expression of TNFα protein by enzyme-linked immunosorbent assay and expression of IL-1ß and IL-6 mRNA by real-time polymerase chain reaction. A histologic examination of joint tissue was also performed. For the statistical analysis, analysis of variance with Tukey's post-hoc test was used for comparisons between each group. All data are expressed as mean values and standard deviation, with P < 0.05. RESULTS: Laser treatment with 50 mW was more efficient than 100 mW in reducing cellular inflammation, and decreased the expression of IL-1ß and IL-6. However, the 100 mW treatment led to a higher reduction of TNFα compared with the 50 mW treatment. CONCLUSIONS: LLLT with 50 mW was more efficient in modulating inflammatory mediators (IL-1ß, IL-6) and inflammatory cells (macrophages and neutrophils), which correlated with the histology that showed a reduction in the inflammatory process.

Wound-healing effects of low-level laser therapy in diabetic rats involve the modulation of MMP-2 and MMP-9 and the redistribution of collagen types I and III.

The present study aimed to determine if LLLT restores the balance between mRNA expression of matrix metalloproteinases (MMP-2 and MMP-9) and also the balance between collagen types I and III during the healing process of diabetic wounds. One hundred and twenty male Wistar rats were distributed in Control (untreated non-diabetic rats: UND); Laser (laser treated in non-diabetic rats: LTND); Diabetic (diabetic rats non-laser treated rats: UD); and Diabetic+ Laser (diabetic rats laser treated: DLT) groups. The diabetes model using streptozotocin efficiently induced diabetes, as demonstrated through increased levels of blood glucose. Diode laser (50 mW, 660 nm, 4 J/cm(2), 80 s) was applied a single time after scare induction. Twenty-four hours after LLLT application, rats were euthanized, the scarred areas were collected for MMP-2 and MMP-9 mRNA analysis and also for histological analysis (inflammation and types I and III collagen). The results demonstrated that scare in untreated diabetic rats significantly increased the MMP-2 and MMP-9 expression compared with that in non-diabetic rats (p < 0.05), while LLLT significantly reduced MMP-2 and MMP-9 expression compared with that in untreated diabetic rats (p < 0.05). To conclude, the results also showed that LLLT was able to alter the expression of MMP-9 as well as accelerate the production of collagen and increase the total percentage of collagen type III in diabetic animals.