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PURPOSE: Bioactive molecules are relevant to fight cancer and associated conditions. Quinoxaline is a privileged N-heterocycle, notably as anticancer agents. Herein, we report the evaluation of the quinoxaline derivatives DEQX and OAQX as anticancer agents, as well as in function of their anti-inflammatory and analgesic activities. METHODS: Quinoxalines were synthesized and tested as anticancer agents based on cell viability and Annexin V-FITC apoptosis. Anti-inflammatory activity was evaluated from mouse carrageenan peritonitis and levels of interleukin (IL)-1ß and tumor necrosis factor (TNF)-alfa for enzyme-linked immunosorbent assay. Hot-plate and acetic acid-induced writing test were employed to investigate analgesia. RESULTS: Both reduced the Ht-29 cell viability in a dependent-concentration manner (p < 0.001). Total apoptosis was detected for cells treated with 12.5 and 25 µg/mL of both the compounds for 24 and 48 h (all doses, p < 0.0001). DEQX (all doses, p < 0.01) and OAQX (all doses, p < 0.001) acted in leukocyte migration and decreased the IL-1ß and TNF-ß levels (p < 0.05). DEQX (all doses, p < 0.05) and OAQX (5mg/kg, p < 0.001) showed peripheral analgesic effect. CONCLUSIONS: In-vitro and in-vivo results suggest that these quinoxalines are promising for application in pharmacological area due to their anticancer, anti-inflammatory, and peripheric analgesia.
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Analgésicos , Anti-Inflamatórios , Antineoplásicos , Apoptose , Sobrevivência Celular , Quinoxalinas , Animais , Quinoxalinas/farmacologia , Quinoxalinas/uso terapêutico , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antineoplásicos/farmacologia , Camundongos , Apoptose/efeitos dos fármacos , Humanos , Sobrevivência Celular/efeitos dos fármacos , Interleucina-1beta/metabolismo , Fator de Necrose Tumoral alfa/análise , Masculino , Células HT29 , Ensaio de Imunoadsorção Enzimática , Peritonite/tratamento farmacológicoRESUMO
INTRODUCTION: Caffeine is a widely consumed substance with several effects on bone metabolism. This study aimed to investigate the effect of caffeine on the bone tissue of rats submitted to orthodontic movement. METHODS: Twenty-five male Wistar rats underwent orthodontic movement (21 days) of the first permanent maxillary molars on the left side. The experimental group (caffeine; n = 13) and control group (n = 12) received caffeine and water, respectively, by gavage. Microcomputed tomography was performed to analyze orthodontic movement. Histologic analysis of the inflammatory infiltrate and osteoclast count by tartrate-resistant acid phosphatase were conducted. Maxilla tissue was evaluated for receptor activator of nuclear factor Ò¡B (RANK), RANK ligand (RANKL), and osteoprotegerin by immunohistochemistry. RESULTS: Caffeine exhibited a lower bone volume/tissue volume ratio (78.09% ± 5.83%) than the control (86.84% ± 4.89%; P <0.05). Inflammatory infiltrate was increased in the caffeine group compared with the control group (P <0.05). A higher number of tartrate-resistant acid phosphatase-positive cells was observed in the caffeine (9.67 ± 1.73) than in the control group (2.66 ± 0.76; P <0.01). Immunoexpression of RANK and RANKL in the caffeine group was greater than the control (P <0.05). CONCLUSIONS: The use of caffeine thermogenic induces alveolar bone loss in rats submitted to orthodontic movement via activation of RANK, RANKL, and osteoprotegerin signaling pathways.
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Perda do Osso Alveolar , Cafeína , Osteoprotegerina , Ligante RANK , Receptor Ativador de Fator Nuclear kappa-B , Técnicas de Movimentação Dentária , Animais , Masculino , Ratos , Perda do Osso Alveolar/metabolismo , Perda do Osso Alveolar/patologia , Cafeína/farmacologia , Maxila/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , Ratos Wistar , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Técnicas de Movimentação Dentária/efeitos adversos , Microtomografia por Raio-XRESUMO
BACKGROUND: (-)-Fenchone is a naturally occurring monoterpene found in the essential oils of Foeniculum vulgare Mill., Thuja occidentalis L., and Peumus boldus Molina. Pharmacological studies have reported its antinociceptive, antimicrobial, anti-inflammatory, antidiarrheal, and antioxidant activities. METHODS: The preventive antiulcer effects of (-)-Fenchone were assessed through oral pretreatment in cysteamine-induced duodenal lesion models. Gastric healing, the underlying mechanisms, and toxicity after repeated doses were evaluated using the acetic acid-induced gastric ulcer rat model with oral treatment administered for 14 days. RESULTS: In the cysteamine-induced duodenal ulcer model, fenchone (37.5-300 mg/kg) significantly decreased the ulcer area and prevented lesion formation. In the acetic acid-induced ulcer model, fenchone (150 mg/kg) reduced (p < 0.001) ulcerative injury. These effects were associated with increased levels of reduced glutathione (GSH), superoxide dismutase (SOD), interleukin (IL)-10, and transforming growth factor-beta (TGF-ß). Furthermore, treatment with (-)-Fenchone (150 mg/kg) significantly reduced (p < 0.001) malondialdehyde (MDA), myeloperoxidase (MPO), interleukin-1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), and nuclear transcription factor kappa B (NF-κB). A 14-day oral toxicity investigation revealed no alterations in heart, liver, spleen, or kidney weight, nor in the biochemical and hematological parameters assessed. (-)-Fenchone protected animals from body weight loss while maintaining feed and water intake. CONCLUSION: (-)-Fenchone exhibits low toxicity, prevents duodenal ulcers, and enhances gastric healing activities. Antioxidant and immunomodulatory properties appear to be involved in its therapeutic effects.
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Apical periodontitis (AP) is a condition characterized by inflammatory and infectious components in the tooth canal. AP affects periradicular tissues and has systemic repercussions. Physical exercise is a structured activity that requires cardiorespiratory function, and can modulate the inflammatory profile in pathological conditions. As a result, this study aimed to determine the effects of aerobic physical training (PT) on the alveolar bone with and without AP, and its systemic inflammatory repercussions. AP was induced in the mandibular first molars, and PT was performed on a treadmill for five consecutive days over four weeks, with progressive increases in speed and activity time. Blood samples were collected to determine serum cytokine levels using immunoassays, and alveolar bone samples were collected for histopathological evaluation, lesion volume and microarchitecture assessment using computed microtomography. Animals with AP had increased pro-inflammatory cytokines levels compared to those without AP; however, these levels were attenuated or restored by PT. Compared to the AP group, the AP + PT group had a smaller lesion volume and greater preservation of the bone trabeculae in the remaining alveolar bone surrounding the lesion. In overall, PT minimized the severity of AP proving to be a valid strategy for individuals undergoing endodontic treatment.
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Citocinas , Periodontite Periapical , Humanos , Animais , Periodontite Periapical/terapia , Periodontite Periapical/patologia , Exercício Físico , Osso e Ossos/patologiaRESUMO
ETHNOPHARMACOLOGY RELEVANCE: Commiphora leptophloeos (Mart.) J.B. Gillet (Burseraceae) is a medicinal plant native to Brazil, popularly known as "imburana". Homemade leaf decoction and maceration were used to treat general inflammatory problems in the Brazilian Northeast population. Our previous research confirmed the anti-inflammatory activity of the C. leptophloeos hydroalcoholic leaf extract. AIM OF THE STUDY: Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gut with no ideal treatment to maintain the remissive status. This work aimed to characterize the phytochemical composition and physicochemical properties of the C. leptophloeos hydroalcoholic leaf extract and its efficacy in chemopreventive and immunomodulatory responses in inflammatory bowel disease in non-clinical models. MATERIALS AND METHODS: Mass spectrometry and physicochemical tests determined the phytochemical profile and physicochemical characteristics of the Commiphora leptophloeos (CL) extract. The chemopreventive and immunomodulatory effects of CL extract (50 and 125 µg/mL) were evaluated in vitro in the RAW 264.7 lipopolysaccharide (LPS) induced cell assay and in vivo in the model of intestinal inflammation induced by 2,4-Dinitrobenzenesulfonic acid (DNBS) in mice when they were treated with CL extract by intragastric gavage (i.g.) at doses of 300, 400 and 500 mg/kg. RESULTS: Phytochemical annotation of CL extract showed a complex phenolic composition, characterized as phenolic acids and flavonoids, and satisfactory physicochemical characteristics. In addition, CL extract maintained the viability of RAW macrophages, reduced ROS and NO production, and negatively regulated COX-2, iNOS, TNF-α, IL-1ß, IL-6, and IL-17 (p < 0.05). In the intestinal inflammation model, CL extract was able to downregulate NF-κB p65/COX-2, mTOR, iNOS, IL-17, decrease levels of malondialdehyde and myeloperoxidase and cytokines TNF-α, IL-1ß and IL-6 (p < 0.05). CONCLUSION: Based on these findings, CL extract reduced inflammatory responses by down-regulating pro-inflammatory markers in macrophages induced by LPS and DNBS-induced colitis in mice through NF-κB p65/COX-2 signaling. CL leaf extract requires further investigation as a candidate for treating inflammatory bowel disease.
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Dinitrofluorbenzeno/análogos & derivados , Doenças Inflamatórias Intestinais , Extratos Vegetais , Camundongos , Animais , Extratos Vegetais/efeitos adversos , Commiphora , Interleucina-17 , Fator de Necrose Tumoral alfa , NF-kappa B , Interleucina-6 , Lipopolissacarídeos/farmacologia , Ciclo-Oxigenase 2 , Doenças Inflamatórias Intestinais/tratamento farmacológico , Inflamação/tratamento farmacológico , Compostos Fitoquímicos/uso terapêuticoRESUMO
PURPOSE: To evaluate the long-chain fatty acid and major compounds levels in the feces after prophylactic oral use of Lacticaseibacillus casei in an experimental model of intestinal mucositis. METHODS: Fifteen Swiss mice were randomly divided into three groups (n=5/group): The negative or positive control groups (n = 5) received saline orally for 18 days and an the intraperitoneal (i.p.) of saline or 5 Fluorouracil (450 mg/kg) in 15th day, respectability. L. casei group received oral concentration of L. casei (1x109 CFU/mL) for 18 days, the i.p. injection of 5-fluorouracil (450 mg/kg) in 15th days. Tissue samples from colon and each small intestine segment were collected for histopathological analysis. Stool samples were collected. Fecal composition of long-chain fatty acids and sterols were analysed by gas chromatography-mass spectrometry on the 15th and the 18th day. RESULTS: The mucosa layer of all small intestine segments of animals from L. casei showed well preserved epithelium and glands, without necrosis signs, but Goblet cells number decreased. Several long-chain fatty acids and sterols have been identified before and after in the groups. L. casei administration after 5-FU treatment reduced concentrations of linoleic acid (18:2) (p < 0.001) and oleic acid (18:1) (p < 0.001) in feces. CONCLUSIONS: L. casei prevented the mucosal damage associated with 5-FU-induced intestinal mucositis reduced long-chain fatty acid levels in the feces.
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Lacticaseibacillus casei , Mucosite , Camundongos , Animais , Mucosite/induzido quimicamente , Mucosite/tratamento farmacológico , Mucosite/prevenção & controle , Lacticaseibacillus , Mucosa Intestinal/patologia , Fluoruracila/efeitos adversos , Ácidos Graxos/efeitos adversos , Esteróis/efeitos adversos , Modelos TeóricosRESUMO
AIMS: Our main goals were to investigate the effects of L-glutathione (1%) treatment in Walker-256 tumor-bearing rats by analyzing immunoreactive neurons (IR), responsive to the nNOS enzyme and 3-Nitrotyrosine, in their jejunum myenteric plexus. Moreover, the oxidative state and inflammatory process in these animals were investigated. METHODS: Four experimental groups were utilized: control (C), control treated with L-glutathione (CGT), Walker-256 tumor-bearing rats (TW), and Walker-256 tumor-bearing rats treated with L-glutathione (TWGT). After 14 days of tumor inoculation, the jejunum was collected for immunohistochemical techniques and assessment of oxidative status. Plasma was collected to evaluate oxidative status and measure cytokines. RESULTS: The TW group exhibited a decrease of reduced glutathione in their jejunum, which was prevented in the L-glutathione treated TWGT group. TW animals presented pronounced oxidative stress by increasing levels of lipoperoxidation in their jejunum and malondialdehyde in their plasma; however, the L-glutathione treatment in TWGT group was not able to avoid it. The total antioxidant capacity was altered in groups TW and TWGT, yet the last one had a better index in their plasma. The IL-10, and TNF-α levels increased in TWGT animals. The nNOS-IR neuron density decreased in the jejunum myenteric plexus of the TW group, which was avoided in the TWGT group. The nNOS +3-Nitrotyrosine neurons quantification did not show significative alterations. CONCLUSION: The treatment with L-glutathione (1%) imposed an important defense to some parameters of oxidative stress induced by TW-256, leading to neuroprotection to the loss in the nNOS-IR neuron density.
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Neoplasias , Neurônios Nitrérgicos , Ratos , Animais , Jejuno , Ratos Wistar , Neuroproteção , Estresse Oxidativo , Glutationa/metabolismo , Plexo Mientérico/patologia , Neoplasias/metabolismo , Neoplasias/patologiaRESUMO
PURPOSE: To evaluate the effects of the experimental subcutaneous Walker-256 tumor and L-glutamine supplementation, an antioxidant, on the glomerular morphology of rats. METHODS: Twenty Wistar rats were distributed into four groups (n = 5): control (C); control treated with 2% L-glutamine (CG); rats with Walker-256 tumor (WT); and rats with Walker-256 tumor treated with 2% L-glutamine (WTG). Renal histological samples were submitted to periodic acid-Schiff and Masson's Trichrome staining to analyze glomerular density, morphometry of glomerular components and glomerulosclerosis; and to immunohistochemistry for fibroblast growth factor-2 (FGF-2). RESULTS: WT showed 50% reduction in body mass gain and cachexia index > 10%, while WTG demonstrated reduction in cachexia (p < 0.05). WT revealed reduction of glomerular density, increase in the glomerular tuft area, mesangial area, matrix in the glomerular tuft, decrease in the urinary space and synechia, and consequently higher glomerulosclerosis (p < 0.05). L-glutamine supplementation in the WTG improved glomerular density, and reduced glomerular tuft area, urinary space, mesangial area, and glomerulosclerosis compared to WT(p < 0.05). WT showed higher collagen area and FGF-2 expression compared to C (p < 0.05). WTG presented lower collagen fibers and FGF-2 expression compared to WT (p < 0.05). CONCLUSIONS: L-glutamine supplementation reduced cachexia and was beneficial for glomerular morphology of the rats, as well as it reduced kidney damage and improved the remaining glomeruli morphology.
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Glutamina , Neoplasias , Ratos , Animais , Ratos Wistar , Glutamina/farmacologia , Caquexia/metabolismo , Caquexia/patologia , Fator 2 de Crescimento de Fibroblastos , Suplementos Nutricionais , ColágenoRESUMO
Os benzodiazepínicos estão entre os medicamentos mais prescritos, principalmente em países ocidentais, onde estimativas mostram um consumo anual de 1% a 3% da população.Objetivo:Estudar o perfil do consumo dos benzodiazepínicosnos anos de 2019-2020. Metodologia:Foram estudadas a taxa de desocupação segundo o Instituto Brasileiro de Geografia e Estatística, consumo dos benzodiazepínicosa partir do Sistema Nacional de Gerenciamento de Produtos Controlados da Agencia de Vigilância Sanitáriae quantidade de internações por envenenamento com exposição (acidental ou proposital), auto-intoxicação e efeitos adversos aos anticonvulsivantes, sedativos, hipnóticos, antiparkinsonianos e psicotrópicos segundo o Departamento de Informática do Sistema Único de Saúde no Brasil. Resultados:A região Norte e Nordeste apresentou um aumento na taxa de desocupação. O rendimento nominal mensal domiciliar per capitada população residente nas regiões Norte e Nordeste se manteveabaixo de 01 salário-mínimo nos anos de 2019 e 2020. De 2019 para 2020, o princípio ativo mais utilizado dos benzodiazepínicos industrializados foi o Clonazepam com incremento de 9,81% no Brasil e 22,52% na região Nordeste. Todas as formas farmacêuticas manipuladas apresentaram umaredução no consumo de 2019 para 2020, com exceção da forma em mililitros que apresentou um incremento para o bromazepam (42,1%), clonazepam (8,76%) e diazepam (5,27%). De 2020 em relação a 2019, ocorreu um incrementode 119,05% e 25% nas regiões Nordeste e Centro-Oeste, respectivamente, nasinternações por envenenamento [intoxicação] por exposição, a anticonvulsivantes (antiepilépticos), sedativos, hipnóticos, antiparkinsonianos e psicotrópicos não classificados em outra parte, intenção não determinada. Conclusões:Ocorreu um aumento no consumo de benzodiazepínicosindustrial no ano de 2020 sendo o envenenamento [intoxicação] umadas principais causasde internação. Há necessidade de um controle do consumo e vigilância aos psicotrópicos visto que estes fármacos estão dentre aqueles com risco de internações devido àexposição acidental ou não, autointoxicaçãoou efeitos adversos (AU).
Benzodiazepines are among the most prescribed drugs, especially in Western countrieswhere estimates show an annual consumption of 1% to 3% of the population.Objective: To study the profile of benzodiazepinesconsumptionfrom the National Controlled Products Management System of the Sanitary Surveillance Agencyin the years 2019 and 2020.Methodology:The unemployment rate,according to theBrazilian Institute of Geography and Statistics,benzodiazepines consumptionfrom the National Controlled Products Management System of the Sanitary Surveillance Agency, and the number of hospitalizations due to poisoning with exposure (accidental or intentional), self-intoxication, and adverse effects to anticonvulsants, sedatives, hypnotics, antiparkinsonian drugs and psychotropic drugs according to the Department of Informatics of the Unified Health System in Brazil were studied.Results:The North and Northeast regions showed an increase in the unemployment rate. The nominal monthly household income per capita of the population residing in the North and Northeast regions remained below 01 minimum wage in the years 2019 and 2020. From 2019 to 2020, the most used active substanceof industrialized benzodiazepines was Clonazepam with an increase of 9.81% in Brazil and 22.52% in the Northeast region. All compounded pharmaceutical forms showed a reduction in consumption from 2019 to 2020, with the exception of the form in milliliters which showed an increase for bromazepam (42.1%), clonazepam (8.76%) and diazepam (5.27%). In 2020 compared to 2019, there was an increase of 119.05% and 25% in the Northeast and Midwest regions, respectively, in hospitalizations for poisoning[intoxication] due to exposure toanticonvulsants (antiepileptics), sedatives, hypnotics, antiparkinsonian drugs,and psychotropic drugs not elsewhere classified with intent undetermined.Conclusions:There was an increase in the consumption of industrial benzodiazepines in 2020, with poisoning [intoxication] being one of the main causes of hospitalization. There is a need to control the consumption andincrease the surveillance of psychotropic drugs becausethese drugs are among those that involverisk of hospitalization due to accidental or non-accidental exposure, self-intoxication or adverse effects (AU).
ntroducción: Las benzodiacepinas se encuentran entre los fármacos más recetados, especialmente en los países occidentales, donde se estima que de 1% al 3% de la poblaciónde estos países los consumen. Objetivo: Estudiar el perfil del consumo de benzodiacepinas en los años 2019-2020.Metodología: Se midieron la tasa de desempleo según elInstituto Brasileño de Geografía y Estadística, el consumo de benzodiacepinasdel Sistema Nacional de Gestión de Productos Controlados de la Agencia de Vigilancia Sanitariay el número de hospitalizaciones por intoxicación con exposición (accidental o intencional), además se estudiaron autointoxicaciones y efectos adversos a los anticonvulsivos, sedantes, hipnóticos, drogas contra el mal de Parkinsony psicotrópicossegún elDepartamento de Informática del Sistema Único de Salud de Brasil.Resultados: Las regiones Norte y Nordeste presentaron aumento de la tasa de desempleo. El ingreso nominal mensual de los hogares per cápita de la población residente en las regiones Norte y Nordeste se mantuvo por debajo de 01 salario mínimo en los años 2019-2020. De 2019 a 2020, el principio activo más utilizado de las benzodiacepinas industrializadas fue el clonazepam con un aumento de 9,81% en Brasil y de22,52% en la región Nordeste. Todas las formas farmacéuticas compuestas mostraron una reducción en su consumo de 2019-2020, a excepción de la forma en mililitros que mostró un aumento para bromazepam (42,1%), clonazepam (8,76%) y diazepam (5,27%). En 2020 respecto a 2019, hubo un aumento del 119,05% y 25% en las regiones Noreste y Medio Oeste, respectivamente, en las hospitalizaciones por intoxicación por exposición aanticonvulsivos (antiepilépticos), sedantes, hipnóticos, drogas contra el mal de Parkinsony psicofármacos no clasificados en otra parte conintención indeterminada.Conclusiones: Hubo un aumento en el consumo de benzodiacepinas industriales en 2020, siendo las intoxicaciones una de las principales causas de hospitalización. Existe la necesidad de controlar el consumo y vigilancia de los psicofármacos, ya que estos fármacos se encuentran entre los de riesgo de hospitalización por exposición accidental o no accidental, autointoxicación o efectos adversos (AU).
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Humanos , Masculino , Feminino , Psicotrópicos/efeitos adversos , Benzodiazepinas/efeitos adversos , Uso de Medicamentos , Brasil/epidemiologia , Estudos Ecológicos , Medicamentos sob Prescrição/efeitos adversosRESUMO
OBJECTIVE: To evaluate the levels of oxidative stress markers in the saliva of patients with oral lichen planus (OLP). METHODS: A cross-sectional study was conducted with 22 patients diagnosed both clinically and histologically with OLP (reticular or erosive) and 12 individuals without OLP. Non-stimulated sialometry was performed and oxidative stress (myeloperoxidase - MPO and malondialdehyde - MDA) and antioxidant (superoxide dismutase - SOD and glutathione - GSH) markers were determined in the saliva. RESULTS: Among the patients with OLP, most were women (n = 19; 86.4%) and reported to have experienced menopause (63.2%). Patients with OLP were mostly in the active stage of the disease (n = 17; 77.3%) and the reticular form was predominant (n = 15; 68.2%). No statistically significant differences were observed when comparing SOD, GSH, MPO and MDA values between individuals with and without OLP, as well as between erosive and reticular forms of OLP (p > 0.05). Patients with inactive OLP presented higher SOD when compared to those with active disease (p = 0.031). CONCLUSION: Oxidative stress markers in the saliva of patients with OLP were similar to those found in people without OLP, which can be related to the high exposure of the oral cavity environment to several physical, chemical and microbiological stimuli, important generators of the oxidative stress.
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Líquen Plano Bucal , Saliva , Humanos , Feminino , Masculino , Líquen Plano Bucal/patologia , Estudos Transversais , Biomarcadores/metabolismo , Estudos de Casos e Controles , Estresse Oxidativo , Glutationa , Superóxido DismutaseRESUMO
Phenolic compounds have been scientifically recognized as beneficial to intestinal health. The cactus Nopalea cochenillifera, used as anti-inflammatory in traditional medicine, is a rich source of these bioactive compounds. The present study aimed to investigate the phytochemical profile of N. cochenillifera extract and evaluate its acute toxicity and anti-inflammatory effect on 2,4-dinitrobenzenesulfonic acid (DNBS)-induced colitis in rats. The total phenolic content per gram of dry extract was 67.85 mg. Through HPLC-IES-MSn, a total of 25 compounds such as saccharides, organic acids, phenolic acids and flavonoids were characterized. The dose of 2000 mg/kg of extract by an oral route showed no signs of toxicity, mortality or significant changes in biochemical and hematological parameters. Regarding intestinal anti-inflammatory effects, animals were treated with three different doses of extract or sulfasalazine. Macroscopic analysis of the colon indicated that the extract decreased the disease activity index. Levels of IL-1ß and TNF-α decreased, IL-10 increased and MDA and MPO enzyme levels decreased when compared with the control group. In addition, a down-regulation of MAPK1/ERK2 and NF-κB p65 pathway markers in colon tissue was observed. The epithelial integrity was improved according to histopathological and immunohistological analysis. Thus, the extract provided strong preclinical evidence of being effective in maintaining the remission of colitis.
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BACKGROUND: Gingival pigmentation is a discoloration of the gingiva due to a variety of lesions and conditions associated with several endogenous and exogenous etiologic features. OBJECTIVE: The purpose of this study is to describe a report of gingival pigmentation in a patient who used doxycycline. CASE REPORT: A 21-year-old Caucasian female was under dermatological treatment and antibiotic therapy with doxycycline 100 mg (one time a day) for 90 days. She presented brown pigmentation at the gingival margin on the facial surfaces of the upper and lower anterior incisors and premolars. The patient was evaluated by immunohistochemical (S-100, Melan-A, and HMB-45) and histopathologic analyses, and clinical history. Blood levels of malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) were analyzed by UV/Vis spectroscopy. The adrenaline, noradrenaline, and dopamine in blood were analyzed by high-performance liquid chromatography (HPLC); dehidroepiandrosterone (DHEA) in serum by radioimmunoassay; and luteinizing hormone (LH) and 25-Hydroxyvitamin D by chemiluminescence. Hematoxylin-eosin stained sections revealed keratinocytes with pigment compatible with melanin. The Fontana-Masson staining was positive in melanophages and in some basal keratinocytes. S-100, Melan A and HMB-45 were confirmed as positive markers of melanocytic differentiation in gingival tissue. We observed a significant increase in malondialdehyde (pË0.05) and a decrease in superoxide dismutase levels (pË0.05). The dopamine value was found to be 15 pg/ml (reference value ≤ 10 pg/ml). CONCLUSION: The use of doxycycline is associated with an increase in oxidative stress and of dopamine with melanin pigments in the gingival tissue. This case report showed a cause-effect relationship between exposure to doxycycline and pigmentation of the marginal gingiva.
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Doxiciclina , Gengiva , Humanos , Feminino , Adulto Jovem , Adulto , Gengiva/química , Doxiciclina/efeitos adversos , Doxiciclina/análise , Melaninas/análise , Dopamina/análise , Superóxido Dismutase/análise , Malondialdeído/análiseRESUMO
Purpose: To evaluate the long-chain fatty acid and major compounds levels in the feces after prophylactic oral use of Lacticaseibacillus casei in an experimental model of intestinal mucositis. Methods: Fifteen Swiss mice were randomly divided into three groups (n=5/group): The negative or positive control groups (n = 5) received saline orally for 18 days and an the intraperitoneal (i.p.) of saline or 5 Fluorouracil (450 mg/kg) in 15th day, respectability. L. casei group received oral concentration of L. casei (1x109 CFU/mL) for 18 days, the i.p. injection of 5-fluorouracil (450 mg/kg) in 15th days. Tissue samples from colon and each small intestine segment were collected for histopathological analysis. Stool samples were collected. Fecal composition of long-chain fatty acids and sterols were analysed by gas chromatography-mass spectrometry on the 15th and the 18th day. Results: The mucosa layer of all small intestine segments of animals from L. casei showed well preserved epithelium and glands, without necrosis signs, but Goblet cells number decreased. Several long-chain fatty acids and sterols have been identified before and after in the groups. L. casei administration after 5-FU treatment reduced concentrations of linoleic acid (18:2) (p < 0.001) and oleic acid (18:1) (p < 0.001) in feces. Conclusions: L. casei prevented the mucosal damage associated with 5-FU-induced intestinal mucositis reduced long-chain fatty acid levels in the feces.
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Doenças Inflamatórias Intestinais , Mucosite , Ácidos Graxos , Lacticaseibacillus caseiRESUMO
Purpose: To evaluate the effects of the experimental subcutaneous Walker-256 tumor and L-glutamine supplementation, an antioxidant, on the glomerular morphology of rats. Methods: Twenty Wistar rats were distributed into four groups (n = 5): control (C); control treated with 2% L-glutamine (CG); rats with Walker-256 tumor (WT); and rats with Walker-256 tumor treated with 2% L-glutamine (WTG). Renal histological samples were submitted to periodic acid-Schiff and Masson's Trichrome staining to analyze glomerular density, morphometry of glomerular components and glomerulosclerosis; and to immunohistochemistry for fibroblast growth factor-2 (FGF-2). Results: WT showed 50% reduction in body mass gain and cachexia index > 10%, while WTG demonstrated reduction in cachexia (p < 0.05). WT revealed reduction of glomerular density, increase in the glomerular tuft area, mesangial area, matrix in the glomerular tuft, decrease in the urinary space and synechia, and consequently higher glomerulosclerosis (p < 0.05). L-glutamine supplementation in the WTG improved glomerular density, and reduced glomerular tuft area, urinary space, mesangial area, and glomerulosclerosis compared to WT(p < 0.05). WT showed higher collagen area and FGF-2 expression compared to C (p < 0.05). WTG presented lower collagen fibers and FGF-2 expression compared to WT (p < 0.05). Conclusions: L-glutamine supplementation reduced cachexia and was beneficial for glomerular morphology of the rats, as well as it reduced kidney damage and improved the remaining glomeruli morphology.
Assuntos
Animais , Ratos , Carcinoma 256 de Walker , Ratos Wistar , Glutamina , Glomérulos Renais , AntioxidantesRESUMO
Background: Intestinal mucositis is one of the most common and important side effects of 5-fluorouracil (5-FU). Currently, there are still no specific and effective protocols for its prevention and treatment. The aim of the present study was to evaluate the effect of oral administration of Lacticaseibacillus casei (L. casei) on the progression of 5-FU-induced intestinal mucositis. Methods: L. casei (1x109 CFU/ml) or saline was orally administered to Swiss mice, beginning 15 days before intestinal mucositis induction by single intraperitoneal 5-FU administration (450 mg/kg). Body weight, number of peripheral leukocytes and fecal lactic acid bacteria were monitored. After euthanasia, on day 18, tissue samples from colon and each small intestine segment were collected for histopathology. Jejunal tissues were collected and evaluated for iNOS and TNF-alpha immunoexpression, IL-1-beta, IL-6 and TNF-alpha levels, malonaldehyde (MDA) accumulation, invertase activity and factor nuclear kappa B (NFkB-P65) gene expression, toll like receptor-4 (TLR-4), mucin-2 (MUC-2), occludin and zonula occludens-1 (ZO-1). Results: The positive impact of L. casei on 5-FU-induced leukopenia was observed, but not on 5-FU-induced weight loss in mice. L. casei reduced 5-FU-induced inflammation in the colon and small intestine (p<0.05). Decreased TNF-α, IL-1ß, IL-6 (p<0.05) and MDA (p<0.05) levels, as well as decreased iNOS and TNF-alpha protein expressions (p<0.05) were found in the jejunum from L casei group. In addition, L-casei down-regulated NFKB-P65 (p<0.05) and TLR-4 (p<0.05) gene expressions and up-regulated MUC-2 and mucosal barrier proteins occludin and ZO-1 gene expressions (p<0.05). Furthermore, greater lactic acid bacteria population (p<0.05) was found in the L. casei group when compared to control groups. Conclusion: Oral L. casei administration can protect the intestine of Swiss mice from 5-FU-induced intestinal mucositis, thus contributing to overall health.
Assuntos
Lacticaseibacillus casei , Mucosite , Camundongos , Animais , Fluoruracila/farmacologia , Mucosite/induzido quimicamente , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Ocludina/metabolismo , Mucosa Intestinal/metabolismo , Intestino Delgado/metabolismo , Colo/patologiaRESUMO
This study aimed to analyze the effects of the quercetin (100 mg/kg), 1% glutamine and 1% α-tocopherol antioxidants in the myocardium of rats with streptozotocin-induced diabetes mellitus. Twenty male rats were subdivided into four groups (n = 5): N (normoglycemic); D (diabetic); NT (normoglycemic treated with antioxidants); and DT (diabetic treated with antioxidants) treated for 60 days. Clinical parameters, oxidative stress markers, inflammatory cytokines, myocardial collagen fibers and immunoexpression of superoxide dismutase 1 (SOD-1), glutathione peroxidase-1 (GPx-1), interleukin-1ß (IL-1-ß), transforming growth factor-beta (TGF-ß), and fibroblast growth factor-2 (FGF-2) were evaluated. Results showed reduced body weight, hyperphagia, polydipsia and hyperglycemic state in groups D and DT. The levels of glutathione (GSH) were higher in NT and DT compared to N (p < 0.01) and D (p < 0.001) groups, respectively. Greater GSH levels were found in DT when compared to N animals (p < 0.001). In DT, there was an increase in IL-10 in relation to N, D and NT (p < 0.05), while GPx-1 expression was similar to N and lower compared to D (p < 0.001). TGF-ß expression in DT was greater than N (p < 0.001) group, whereas FGF-2 in DT was higher than in the other groups (p < 0.001). A significant reduction in collagen fibers (type I) was found in DT compared to D (p < 0.05). The associated administration of quercetin, glutamine and α-tocopherol increased the levels of circulating interleukin-10 (IL-10) and GSH, and reduced the number of type I collagen fibers. Combined use of systemic quercetin, glutamine and alpha-tocopherol attenuates myocardial fibrosis in diabetic rats.
Assuntos
Diabetes Mellitus Experimental , Quercetina , Animais , Antioxidantes/metabolismo , Colágeno/metabolismo , Diabetes Mellitus Experimental/metabolismo , Fator 2 de Crescimento de Fibroblastos/metabolismo , Fibrose , Glutamina/metabolismo , Glutationa/metabolismo , Interleucina-10/metabolismo , Masculino , Estresse Oxidativo , Quercetina/farmacologia , Quercetina/uso terapêutico , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Fator de Crescimento Transformador beta/metabolismo , alfa-Tocoferol/farmacologia , alfa-Tocoferol/uso terapêuticoRESUMO
PURPOSE: This study aimed to evaluate the effects and mechanisms of action of royal jelly (RJ) and propolis compared to photobiomodulation therapy (PBMT) in an animal model of 5-fluorouracil-related oral mucositis (OM). METHODS: Seventy-two male Wistar rats were randomly allocated to four groups (n = 18 each): control (no treatment), PBMT (intraoral laser, 6 J/cm2), RJ, and propolis. On days 0 and 2, the animals received an injection of 5-fluorouracil (5-FU). The buccal mucosa was scratched (days 3 and 4) and the treatments were initiated on day 5. Six animals of each group were euthanized on days 8, 10, and 14. Phytochemical analysis (thin-layer chromatography, TLC) and clinical, histopathological, and immunohistochemical analysis of pS6, pAKT, and NF-κB were performed, and oxidative stress markers were also investigated. RESULTS: TLC revealed the presence of large amounts of sucrose (Rf 0.34) in RJ and of flavonoids in propolis. Lower clinical OM scores were observed on day 8, and improved morphological data were observed on day 10 in the PBMT, RJ, and propolis groups (p < 0.05). On day 8, immunoexpression of pS6, pAKT, and NF-κB was increased compared to control. On day 14, reduced glutathione (GSH) antioxidant levels were increased in the propolis group compared to control (p < 0.05). CONCLUSIONS: Our results showed that RJ and propolis, as well as PBMT, are effective in the treatment of OM. Considering that some patients who develop OM do not have access to PBMT, the present study demonstrated that topical application of RJ and propolis may be an important alternative for the treatment of OM.
Assuntos
Terapia com Luz de Baixa Intensidade , Própole , Estomatite , Animais , Ácidos Graxos , Fluoruracila , Humanos , Masculino , Ratos , Ratos Wistar , Estomatite/induzido quimicamente , Estomatite/terapiaRESUMO
Abstract Curcumin, contained at Turmeric (Curcumalonga), can exert many beneficial pleiotropic activities in the gastrointestinal tract. This study evaluated the antioxidant and anti-inflammatory activity of C. longa on 5-fluorouracil (5-FU)-induced oral mucositis (OM) in hamsters. Phytochemical analysis of crude C. longa extract (CLE) was performed to detect the presence of curcumin by TLC and HPLC. Golden Syrian hamsters were orally pre-treated with CLE (5, 50, or 100mg/kg). Cheek pouch samples were subjected to macroscopic and histopathological evaluation. ELISA was performed to quantify the inflammatory cytokines IL-1ß and TNF-α. Superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) levels were assessed by ultraviolet-visible spectroscopy analysis. Behavior analysis was conducted by the open field test. Curcumin content in the CLE was 0.55%m/m ± 0.0161 (2.84%). The group treated with 5mg/kg CLE showed healing evidence with macroscopic absence of ulceration (p<0.05) and microscopic aspect of re-epithelialization, discrete inflammatory infiltrate and absence of edema. Treatment with 5mg/kg CLE significantly increased GSH levels, and reduced MDA levels and SOD activity (pË0.05), and decreased IL-1ß (pË0.05) and TNF-α (pË0.01) levels. A significant reduction in walking distance, ambulation, speed, and rearing was observed for motor activity. Curcumin reduced oxidative stress, inflammation, and motor activity in hamsters with 5-FU-induced OM.
Assuntos
Animais , Masculino , Ratos , Estomatite/patologia , Curcumina/análise , Curcuma/classificação , Cromatografia Líquida de Alta Pressão/métodos , Compostos Fitoquímicos/agonistas , Fluoruracila/administração & dosagem , Inflamação/complicações , Antioxidantes/classificaçãoRESUMO
Introdução:Pacientes com depressão maior geralmente respondem ao tratamento com medicamentos antidepressivos, no entanto em 10% a 30% dos casos há apenas uma resposta parcial ou nenhuma resposta, entre os fatores que podem influenciar encontra-se o perfil das enzimas hepáticas metabolizadoras dos antidepressivos, tal como a CYP2C19.Objetivo:Caracterizar os indivíduos quanto ao perfil genético dospolimorfismos CYP2C19*2 ou CYP2C19*17 em pacientes com transtorno depressivo maior (TDM) tratados com citalopram ou escitalopram e compará-los em relação a adesão ao tratamento, sintomas de depressão e qualidade de vida.Metodologia:Trata-se de um estudo transversal realizado com 29 pacientes com TDM. Amostras de sangue foram coletadas para genotipagem de CYP2C19 por discriminação alélica TaqMan®. Após caracterização do perfil genético, os indivíduos foram comparados quanto aos dados demográfico e socioeconômico, adesão ao tratamento (TestedeMorisky-Green),sintomas de depressão (escala de Hamilton) e qualidade de vida (WHOQoL-BREF).Resultados:Quatro pacientes (13.8%) apresentaram polimorfismo para CYP2C19*2 e 10 pacientes (34.4%) para CYP2C19*17, com maior prevalência de CYP2C19*17 (p>0.05). Nenhuma associação significativa de características socioeconômicas, demográficas e clínicas entre os genótipos do CYP2C19.No TestedeMorisky-Green, aadesão moderada ao tratamento foi predominante nos pacientes CYP2C19*2 e CYP2C19*17 (p>0.05). Não foi observada associação entre sintomas de depressão e polimorfismos genéticos (p>0.05). Uma associação significativa entre o genótipo polimórfico CC do CYP2C19*17 com a satisfação com a saúde, enquanto o genótipo CT foi associado ao estado "nem satisfeito/nem insatisfeito" (p<0.05). A maioria dos indivíduos CYP2C19*2 e CYP2C19*17 relatou "necessidade de melhorar" em relação aos domínios de qualidade de vida físico, psicológico, social e ambiental (p>0.05).Conclusões:Os pacientes apresentaram maior prevalência do polimorfismo CYP2C19*17, com moderada adesão ao tratamento. Alguns pacientes, mesmo sob efeito da medicação, apresentaram sintomas de depressão moderado a intenso e relataram uma indefinição na satisfação da sua qualidade de vida (AU).
Introduction:Patients with major depression usually respond to treatment with antidepressant drugs, however in 10% to 30% of cases there is only a partial response or no response, among the factors that can influence is the profile of liver enzymes metabolizing antidepressants, such as CYP2C19.Objective:To characterize the individuals regarding the genetic profile ofCYP2C19*2or CYP2C19*17 polymorphisms in patients with major depressive disorder (MDD) treated with citalopram or escitalopram, and to compare themaccording to treatment adherence, symptoms of depression and quality of life.Methodology:This is cross-sectionalstudy carried out with 29 patients with MDD. Blood samples were collected for CYP2C19 genotyping by TaqMan® allelic discrimination. After characterization of the genetic profile, the individuals were compared regarding the demographic and socioeconomic data, treatment adherence (Morisky-GreenTest), symptoms of depression (Hamilton scale) and quality of life (WHOQoL-BREF).Results:Four patients showed (13.8%) CYP219*2 and 10 patients (34.4%) CYP219*17 polymorphisms.,withhigher prevalence of CYP219*17 (p>0.05). No association between socioeconomic, demographic, and clinical features with CYP2C19 genotypes was observed. In Morisky-GreenTest, moderate adherence to treatment was predominant for CYP2C19*2 and CYP219*17 patients (p>0.05). No statistically significant association was observed between symptoms of depression and genetic polymorphisms (p>0.05). A significant association between polymorphic CC genotype of CYP219*17 with health satisfaction, while the CT genotype was associated with "neither satisfied/nor dissatisfied" status (p<0.05). Most of the CYP2C19*2 and CYP2C19*17 subjects reported "need to improve" or "regular" regarding physical, psychological, social, and environmental domainsof quality of life(p>0.05).Conclusions:The patients showed a higher prevalence of CYP219*17 polymorphism, with moderate treatment adherence. Some subjects, even under the effect of the medication, presented moderate to intense symptoms of depression, and reported a lack of definition in the satisfaction of their quality of life (AU).
Introducción:Los pacientes con depresión mayor responder al tratamiento con antidepresivos, en 10% al 30% de los casos existe una respuesta parcial o nula, entre los factores que pueden influir se encuentra el perfil de enzimas hepáticas metabolizadoras de antidepresivos, como CYP2C19.Objetivo: Caracterizar a los individuos en cuanto al perfil genético depolimorfismos CYP2C19 *2 o CYP2C19 * 17 en pacientes con trastorno depresivo mayor (TDM) tratados con citalopram o escitalopram y compararlos en relaciónpara la adherencia al tratamiento, síntomas de depresión y la calidad de vida.Metodología: Estudio transversalcon 29 pacientes con TDM. Se recogieron muestras de sangre para la determinación del genotipo CYP2C19 mediante discriminación alélica TaqMan®, los individuos fueron comparados en cuanto a los datosdemográficosy socioeconómicos, adherencia (Prueba de Morisky-Green), síntomas de depresión (escala de Hamilton) y calidad de vida (WHOQoL-BREF).Resultados: Cuatro pacientes (13,8%) con polimorfismo CYP2C19*2 y 10 (34,4%) con CYP2C19 * 17,(p> 0,05). No existe una asociación significativa de las características socioeconómicas, demográficas y clínicas con los genotipos CYP2C19. La adherencia moderada al tratamiento fue predominante en los pacientes con CYP2C19*2 y CYP2C19*17 (p> 0,05). No hubo asociación entre síntomas de depresión y polimorfismos genéticos (p> 0.05). Una asociación significativa entre el genotipo polimórfico CYP2C19 * 17 CC con la satisfacción con la salud, mientras que el genotipo CT se asoció con el estado "ni satisfecho / no insatisfecho" (p <0.05). La mayoría de CYP2C19 * 2 y CYP2C19 * 17 individuos informaron "necesidad de mejorar" en relación con los dominios físico, psicológico, social y ambientalde calidad de vida(p> 0,05).Conclusiones: Los pacients mostraron una mayor prevalencia del CYP2C19 * 17, con adherencia moderada al tratamiento, síntomas de depresión moderada a intensay informaron una falta de definición en la satisfacción de su calidad de vida (AU).
Assuntos
Humanos , Citalopram/farmacologia , Depressão/tratamento farmacológico , Transtorno Depressivo Maior/tratamento farmacológico , Citocromo P-450 CYP2C19/farmacologia , Antidepressivos/farmacologia , Qualidade de Vida , Brasil , Estudos Transversais/métodos , Tratamento FarmacológicoRESUMO
Intestinal mucositis (IM) is a common side effect of 5-fluorouracil (5-FU)-based chemotherapy, which negatively impacts therapeutic outcomes and delays subsequent cycles of chemotherapy resulting in dose reductions and treatment discontinuation. In search of new pharmacological alternatives that minimize your symptoms, this work set out to study the effect of losartan (LOS), a receptor type I (AT1) angiotensin II antagonist, on intestinal mucositis induced by 5-FU. Intestinal mucositis was induced by a single intraperitoneal administration of 5-FU (450 mg/kg) in Swiss mice. Losartan (5, 25 or 50 mg/kg) or saline was orally administered 30 min before 5-FU and daily for 4 days. On 4th day, the animals were euthanized and segments of small intestine were collected to evaluate histopathological alterations (morphometric analysis), concentration of inflammatory cytokines, oxidative stress markers and genic expression of NF-κB p65, Fn-14 and TWEAK. Weight evaluation and changes in leukogram were also analyzed. 5-FU induced intense weight loss, leukopenia and reduction in villus height compared to saline group. Losartan (50 mg/kg) prevented 5-FU-induced inflammation by decreasing in the analyzed parameters compared to the 5-FU group. Our findings suggest that 50 mg/kg of losartan prevents the effects of 5-FU on intestinal mucosa in mice.