[Show abstract][Hide abstract] ABSTRACT: Previous studies have demonstrated that hyperoxia-induced stress and oxidative damage to the lungs of mice lead to an increase in IL-6, TNF-α, and TGF-β expression. Together, IL-6 and TGF-β have been known to direct T cell differentiation toward the TH17 phenotype. In the current study, we tested the hypothesis that hyperoxia promotes the polarization of T cells to the TH17 cell phenotype in response to ovalbumin-induced acute airway inflammation. Airway inflammation was induced in female BALB/c mice by intraperitoneal sensitization and intranasal introduction of ovalbumin, followed by challenge methacholine. After the methacholine challenge, animals were exposed to hyperoxic conditions in an inhalation chamber for 24 h. The controls were subjected to normoxia or aluminum hydroxide dissolved in phosphate buffered saline. After 24 h of hyperoxia, the number of macrophages and lymphocytes decreased in animals with ovalbumin-induced airway inflammation, whereas the number of neutrophils increased after ovalbumin-induced airway inflammation. The results showed that expression of Nrf2, iNOS, T-bet and IL-17 increased after 24 of hyperoxia in both alveolar macrophages and in lung epithelial cells, compared with both animals that remained in room air, and animals with ovalbumin-induced airway inflammation. Hyperoxia alone without the induction of airway inflammation lead to increased levels of TNF-α and CCL5, whereas hyperoxia after inflammation lead to decreased CCL2 levels. Histological evidence of extravasation of inflammatory cells into the perivascular and peribronchial regions of the lungs was observed after pulmonary inflammation and hyperoxia. Hyperoxia promotes polarization of the immune response toward the TH17 phenotype, resulting in tissue damage associated with oxidative stress, and the migration of neutrophils to the lung and airways. Elucidating the effect of hyperoxia on ovalbumin-induced acute airway inflammation is relevant to preventing or treating asthmatic patients that require oxygen supplementation to reverse the hypoxemia.
[Show abstract][Hide abstract] ABSTRACT: Malignant neoplasia represents the second cause of disease-related mortality and, among all patients diagnosed with cancer, 70% will receive chemotherapy during the course of treatment. As a consequence, an increasing number of researchers have focused their attention on the search for more specific anticancer therapies associated with fewer side effects. Leukopenia is an important adverse effect associated with chemotherapy. Secondary infection is very common among leukopenic patients, directly affecting the continuity of the chemotherapeutic treatment and leading to possible complications in tumor immune defense. Atorvastatin, a type of statin, is a known agent used to control hypercholesterolemia. Trans-caryophyllene, isolated from a resinous oil extracted from the copaiba tree, possesses anti-inflammatory and analgesic properties. The AIM of the present study was to evaluate, through a complete leukocyte count, the systemic immunomodulation potential of pentoxifylline (PTX), atorvastatin and trans-caryophyllene, as well as the possible prophylactic role of these drugs against secondary leukopenia, in an experimental chemotherapy model induced by 5-fluorouracil (5-FU) in wistar rats. A total of 32 male wistar rats were used, 24 of which were submitted to treatment with atorvastatin, PTX and trans-caryophyllene prior to the administration of chemotherapy. The Shapiro-Wilk test was used to verify normality and the Kruskal-Wallis test was used for negative data in the normality test. Among the drugs selected, atorvastatin exhibited the best preventive potential in regards to leukopenia secondary to experimental chemotherapy induced by 5-FU, in comparison to the group receiving saline solution, while PTX amplified such alterations in the leukograms of the animals in this trial.
Molecular and Clinical Oncology 04/2015; 3(4). DOI:10.3892/mco.2015.544
[Show abstract][Hide abstract] ABSTRACT: Experimental autoimmune encephalomyelitis (EAE) is a murine autoimmune disease used to study multiple sclerosis. We have investigated the immunomodulatory effects of copaiba oil (100, 50 and 25 µg/mL) on NO, H2O2, TNF-α, IFN-γ and IL-17 production in cultured cells from EAE-mice. Copaiba oil (100 µg/mL) inhibited H2O2, NO, IFN-γ TNF-α and IL-17 production spontaneously or after ConA and MOG35-55 stimulation. It is suggested that copaiba oil acts on the mechanism of development of EAE by IFN-γ, IL-17 and TNF-α inhibition, modulating the immune response on both Th1 and Th17 cells.
[Show abstract][Hide abstract] ABSTRACT: In this work we investigated the in vivo protective effects of Baccharis dracunculifolia leaves extract (BdE) against carbon tetrachloride (CCl4)- and acetaminophen (APAP)-induced hepatotoxicity. Total phenolic content, total flavonoid content, antioxidant DPPH radical scavenging activity, and HPLC analysis were performed. Our results showed that pretreatment with BdE significantly reduced the damage caused by CCl4 and APAP on the serum markers of hepatic injury, AST, ALT, and ALP. Results were confirmed by histopathological analysis. Phytochemical analysis, performed by HPLC, showed that BdE was rich in p-coumaric acid derivatives, caffeoylquinic acids and flavonoids. BdE also showed DPPH antioxidant activity (EC50 of 15.75 ± 0.43 μg/mL), and high total phenolic (142.90 ± 0.77 mg GAE/g) and flavonoid (51.47 ± 0.60 mg RE/g) contents. This study indicated that B. dracunculifolia leaves extract has relevant in vivo hepatoprotective properties.
[Show abstract][Hide abstract] ABSTRACT: Evaluate the effect of the extract of Ginkgo biloba L., Ginkgoaceae (EGb) in the Bcl-2 expression by osteoblasts in the femoral trabecular bone of Wistar rats with glucocorticoid-induced osteoporosis. Rats were divided into five groups: osteoporosis; EGb1 (28 mg/kg); EGb2 (56 mg/kg); alendronate (0.2 mg/animal) and control. The treatments were conducted for 20 or 30 days. The Bcl-2 expression by osteoblasts cells was evaluated in the femoral trabecular bone. The control group was compared with the osteoporosis-induced group (Student's t-test). The other groups were analyzed by ANOVA test followed by Tukey's test (p < 0.05). The percentage of Bcl-2 expression was reduced, when the control group (17.95 ± 3.45 20 days; 21.11 ± 3.43 30 days) was compared with the osteoporosis group (10.64 ± 3.30 20 days; 9.72 ± 2.84 30 days).
Nevertheless, this percentage increased in the EGb2 group (18.58 ± 3.41 20 days; 16.51 ± 1.80 30 days) when compared to the osteoporosis group. The EGb increased the expression of the anti-apoptotic protein, suggesting a decrease in osteoblast apoptosis.
Revista Brasileira de Farmacognosia 06/2014; 24(3):363–366. DOI:10.1016/j.bjp.2014.07.015 · 0.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Oral mucositis is a condition that is characterized by ulcerative lesions in the mucosa of patients undergoing radiotherapy or chemotherapy. Oral mucositis is currently considered to be the most severe complication of anticancer therapy, affecting 40-80% of patients undergoing chemotherapy and almost all those undergoing radiotherapy of the head and neck. Although they do not prevent lesions from appearing, drugs for the treatment of oral mucositis are required to minimize its clinical aggressiveness and improve the nutritional status, hydration and quality of life of the affected patients. Furthermore, the prevention and control of oral ulcers is crucial for cancer prognosis, since the establishment of severe lesions may lead to temporary or permanent treatment discontinuation and compromise cancer control. The objective of this study was to present a review on this condition, its causes and its treatment to professional clinical dentists, in order to help minimize patient suffering. A search was conducted through PubMed, Lilacs and MedLine, to retrieve related articles published between 1994 and 2013.
Molecular and Clinical Oncology 05/2014; 2(3):337-340. DOI:10.3892/mco.2014.253
[Show abstract][Hide abstract] ABSTRACT: The determination of fatty acids (FA) in liver from three different groups of Wistar rats (six rats by group) submitted to diet (AIN-93G) by capillary zone electrophoresis (CZE) was proposed. Each group received the same diet. However, the soybean oil used to prepare the feed, whose amount was 7% w/w, had different origins. The first group was fed with feed containing soybean oil fresh; the second one was fed with soybean used during 7 days in deep frying process; finally, the third was fed with soybean used during 15 days in deep frying process. After 45 days the rats were submitted to euthanasia and the FA amount in liver was successful monitored by CZE in a simple, fast and efficient way. The results obtained were compared to gas chromatography official method and no significant differences were observed within 95% confidence interval. The electropherograms to FA analysis were submitted to principal component analysis (PCA) being possible to discriminate the final from the control and intermediate groups. In addition to PCA results, the low density lipoprotein (LDL) was evaluated indicating that the total time exposure of the oil submitted to deep frying processes can be considered relevant to evaluating the oil quality.
Journal of the Brazilian Chemical Society 04/2014; 25(4). DOI:10.5935/0103-5053.20140015 · 1.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Our objective was to evaluate changes in serum leptin levels during pregnancy in overweight/obese and non-obese women and to assess total and percent weight gain during pregnancy as possible factors that influence leptin levels.
In a prospective study of 42 low-risk pregnant women receiving prenatal care, we assessed serum leptin levels at gestational weeks 9–12, 25–28, and 34–37. Based on their pre-pregnancy body mass indices (BMIs), the cohort was divided into: non-overweight (BMI <25 kg/m2) and overweight/obese (BMI ≥25 kg/m2) subjects.
We found a progressive increase in maternal weight gain during pregnancy in both groups. There was also a progressive increase in leptin levels in the 2 strata; however, the increase was significantly higher in the non-overweight patient group. We found that non-overweight pregnant women had a noticeably larger total weight gain. When analyzing the percent weight gain during pregnancy compared to the pre-pregnancy weight, the non-overweight group had a significantly greater percent weight gain than the overweight/obese group.
Our results suggest that the greater increase in leptin levels in non-overweight pregnant women can be explained by the higher percent weight gain in this group compared to overweight/obese women. These findings suggest that controlling the percent weight gain may be an important preventive measure when controlling leptin levels during pregnancy and subsequent medical complications.
Medical science monitor: international medical journal of experimental and clinical research 11/2013; 19:1043-1049. DOI:10.12659/MSM.884027 · 1.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Oral lichen planus (OLP) is considered a chronic autoimmune inflammatory disease and its presence may be related to increased emotional stress. The clinical relevance of OLP is the possibility of developing a squamous cell carcinoma, the etiology of which is still unknown. The aim of this study is to treat OLP lesions resistant to conventional treatment with corticosteroids, using topical tacrolimus 0.1% (Protopic(®)) twice a day for a period of eight weeks. Fifteen patients were selected who had filled out a history form and a visual analog scale for pain before and after treatment. All patients underwent an initial biopsy to diagnose the disease and another at the end of the treatment period to evaluate the effect of the medication on the infiltrate. A weekly check was carried out, observing the clinical appearance, pain symptoms and occurrence of side effects which, where present, were mild and transient. The results showed twelve patients (80%) with total or nearly total remission of pain symptoms and lesions, two patients (13.33%) showed clearer lesions and only one patient (6.67%) had no change in clinical symptoms or pain. Histopathological analysis showed OLP had a moderate or strong regression in twelve patients (80%) and an absent or mild regression in three patients (20%). Based on these results, it was concluded that tacrolimus 0.1% (Protopic(®)) is a safe and effective medication that improves the clinical appearance of the lesion, reduces pain as well as the histopathological features of OLP.
International Journal of Clinical and Experimental Medicine 11/2013; 6(10):917-921. · 1.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Delayed, or type IV, hypersensitivity reactions are a useful model to study the effects of new substances on the immune system. In this study, the experimental model of the delayed type hypersensitivity (DTH) reaction to ovalbumin (OVA) was used to evaluate the immunomodulating effects of low-level laser therapy (LLLT), which is used as an adjuvant therapy in medicine, dentistry, and physical therapy because of its potential anti-inflammatory and analgesic effects observed in several studies. The effects of LLLT (λ 780 nm, 0.06 W/cm(2) of radiation, and fluency of 3.8 J/cm(2)) in reaction to ovalbumin in Balb/C mice were examined after the induction phase of the hypersensitivity reaction. The animals treated with azathioprine (AZA), the animals that received a vehicle instead of ovalbumin, and those not immunized served as controls (n = 6 for each group). Footpad thickness measurements and hematoxylin-eosin histopathological exams were performed. Proliferation tests were also performed (spontaneous, in the presence of concanavalin A and ovalbumin) to determine the production in mononuclear cells cultures of tumor necrosis factor-alpha (TNF-α), INF-γ, and IL-10. In the group of animals irradiated with lasers and in the group treated with AZA, footpad thickness measurements were significantly reduced in comparison to the control group (p < 0.05). This reduction was accompanied by a very significant reduction in the density of the inflammatory infiltrate and by a significant reduction in the levels of TNF-α, INF-γ, and IL-10. LLLT radiation was shown to have an immunomodulating effect on DTH to OVA in Balb/C mice.
Lasers in Medical Science 01/2013; 28(6). DOI:10.1007/s10103-012-1262-5 · 2.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the correlation between maternal waist circumference measured before the 12th week of gestation and serum leptin levels during pregnancy, as well as to compare the leptin levels of women with and without abdominal obesity diagnosed in early pregnancy.
Prospective study including 40 pregnant women receiving low-risk prenatal care, older than 20 years, nonsmokers, with singleton pregnancies and without chronic disease. Waist circumference was measured before the 12th week and serum leptin levels were measured between the 9th and 12th, 25th and 28th and 34th and 37th weeks of gestation. According to waist circumference measurement, the cohort was divided into two groups: with and without abdominal obesity. The Mann-Whitney and χ(2) tests were used to assess the differences between groups. The Pearson correlation coeffient was used to assess the association between waist circumference and serum leptin levels during pregnancy. The level of significance was set at p<0.05.
The mean weight and body mass index of patients with abdominal obesity (74.4±11.0 kg/28.9±4.1) was higher than that of patients without abdominal obesity (55.6±5.9 kg/21.1±2.4) (p=0.001). The mean leptin levels in pregnant patients with abdominal obesity (41.9±3.5 ng/mL) was higher than in patients without abdominal obesity (23.6±2.7 ng/mL) (p<0.0002). A positive correlation was obtained between the waist circumference measured during the same period and the mean serum leptin levels (r=0.7; p<0.0001).
Waist circumference measured before the 12th week of pregnancy is a valid and simple method to predict the serum leptin levels throughout pregnancy. Pregnant women with abdominal obesity diagnosed before 12th week have higher mean serum leptin levels during pregnancy than those without abdominal obesity.
Revista brasileira de ginecologia e obstetrićia: revista da Federação Brasileira das Sociedades de Ginecologia e Obstetrícia 06/2012; 34(6):268-73. DOI:10.1590/S0100-72032012000600005
[Show abstract][Hide abstract] ABSTRACT: Asthma is a disease characterized by intermittent obstruction of the airways and chronic inflammation that affects approximately 300 million people worldwide. The immune response in asthma is predominantly T(H)2, with high levels of total and allergen-specific IgE and bronchial eosinophilia. Asthma treatment is aimed at controlling the disease, and the drugs used currently have systemic adverse effects and generally are not effective in difficult-to-control cases.
To investigate the effect of aqueous extract of Echinodorus grandiflorus, a plant used in folk medicine for its diuretic and anti-inflammatory properties, in a model of pulmonary allergy.
BALB/c mice were intraperitoneally sensitized and nasally challenged with ovalbumin. Aqueous extract and dexamethasone treatments (0.1 mL/d per mouse) were initiated on day 32 and concluded on day 40. Eight hours after the last challenge evaluations, of serum, bronchoalveolar lavage, and lung tissue were performed.
Oral treatment with the extract markedly reduced the number of total cells and eosinophils in bronchoalveolar lavage. The eosinophil peroxidase activity in lung tissue, the levels of ovalbumin-specific IgE in serum, the levels of CCL11, and the gene expression of interleukin 4 and interleukin 13 in lung tissue were also lower after treatment.
These results suggest that the aqueous extract of E grandiflorus is able to modulate allergic pulmonary inflammation and may be useful as a potential therapeutic agent for asthma.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 06/2011; 106(6):481-8. DOI:10.1016/j.anai.2011.01.008 · 2.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives: to evaluate, by immunohistochemistry, vimentin and osteopontin expression in the repair of bone defects created in femurs of Wistar albinus rats treated with organic bovine bone graft and associated with low level laser therapy. Materials and methods: Histological slides were obtained from blocks of different animals which were divided as follow: group I (control), group II (Gen-Ox ) and group III (LLLT and Gen-Ox ). Four slides of days 3, 5, 7 and 15 were prepared. Two slides were assessed for the expression of osteopontin and two of vimentin. Two fields were considered for analysis: one in the bone-defect interface and the other near the periosteum. To perform the immunohistochemistry anti-vimentin and anti-osteopontin, we used the classical avidin-biotin peroxidase anti-peroxidase method. The positive staining was determined by identification of intracytoplasmic brown color in the reactions with both antibodies. The sections were analyzed in Zeiss microscope at a magnification of 200x, 400x and 1000x by two different observers. The average intensity of positive cells stained in the fields in each period was determined by a semiquantitative counting method which was classified by a scoring system as follow: 0 = no marking; + = mild labeling (up to one third of positive cells); + + = moderate labeling (up to two thirds of positive cells) and + + + = intense labeling (over two thirds of labeled cells). Results: All groups had marked for vimentin and osteopontin in all periods. We observed a stronger cell labeling for vimentin in the initial healing period in group III. There were no differences in cell labeling for osteopontin in animals subjected to low level laser therapy associated with graft as compared to other groups. Conclusion: From the above results, the expression of vimentin and osteopontin during early bone repair was observed within bone tissue.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the possible toxicity of the aqueous extract of Echinodorus grandiflorus in pregnant rats, animals were distributed in groups treated with 250, 500 and 1,000 mg/kg/day, by gavage, and a control group received saline solution. The treatment was carried out for 15 consecutive days, remaining during mating and until the 14(th) day of gestation. On the 15(th )day, pregnant animals were euthanized by exsanguination under anesthesia. A blood sample was destined to the hematological and biochemical analysis. The ovaries, liver, kidneys, spleen, and adrenal glands were removed and weighed. Liver, kidneys and spleen were processed for histopathological analysis. The number mated, cohabitated and pregnant rats were counted as well as the corpora lutea, implants, resorptions, and live and dead fetuses. Fetus body weight and placenta were measured. Treatment with 1,000 mg of extract caused anemia, leukocytosis, and an increase in AST and in cholesterol. The liver of animals treated with the two higher doses exhibited discrete inflammatory reaction, located mainly at the stroma which supports the portal space; in the kidneys of animals of T-500 and T-1000 groups there was an expressive decrease in the capsular space, and focal areas of vasodilatation and congestion, as well as a discrete hyalinization, and in the spleen of T-1000 group the red pulp presented excessive pigmentation suggestive of hemosiderin. There were no alterations in reproductive parameters, in fetus external morphology or in placenta weight. In conclusion, the extract causes maternal toxicity, though it does not alter the reproductive performance.
The Journal of Toxicological Sciences 12/2010; 35(6):911-22. DOI:10.2131/jts.35.911 · 1.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Autoimmune encephalomyelitis (EAE) in Lewis rats is a classical experimental model of demyelinating inflammatory disease of the central nervous system. EAE is widely accepted for study of immune-inflammatory mechanisms in the CNS related to multiple sclerosis (MS) due to similar clinical evolution.
In the present study we investigated the effects of Thalidomide and pentoxifylline during EAE development in Lewis rats.
EAE was induced in Lewis rats and treatment with Thalidomide or pentoxifylline was performed. Clinical evaluation was carried out daily. Histopathological analysis of the brain tissue and spinal cord was performed. Griess method was used for determination of NO serum levels. TNF-alpha and IFN-gamma serum levels were investigated using ELISA method.
Thalidomide and pentoxifylline treatment is associated with significant reduction of neuroinflammation in CNS. Serum levels of NO, IFN-gamma and TNF-alpha showed a marked reduction. Such findings were correlated with improvement of clinical symptoms, particularly in thalidomide treated rats.
Taken together the data suggested that thalidomide and pentoxifylline may be therapeutic options for the treatment of MS, however further experiments must be performed to investigate this hypothesis.