RESUMO
This study aimed to evaluate the effects of safflower oil supplementation on the metabolic parameters, body weight, and abdominal adiposity in male Wistar rats fed with a high-fat diet (HFD) while undergoing exercise training. The rats were assigned to four groups: standard diet and sedentary (SDS), high-fat diet and sedentary (HFDS), high-fat diet and training (HFDT), and high-fat diet, training, and safflower oil (HFDTSO) groups. HFD significantly increased the abdominal adiposity in male Wistar rats. The safflower oil had no effect on the body weight and levels of blood glucose, TG, and TC, but it significantly reduced abdominal adiposity in male Wistar rats fed with an HFD while undergoing exercise training. Safflower oil supplementation reduced the abdominal fat in rats undergoing swimming training.
RESUMO
Seaweeds are sources of biomolecules with biological activities and pharmacological potential - for example, lectins, a group of proteins that can bind reversibly to carbohydrates or compounds containing them. The aim of this study was to elucidate the structural properties of a lectin extracted from the red seaweed Bryothamnion triquetrum (BtL) and to investigate its anti-inflammatory activity in mice. The lectin was purified by precipitation with ammonium sulfate and ion-exchange chromatography. Its secondary structure and tryptophan (Trp) microenvironment were analyzed by circular dichroism spectroscopy and steady-state fluorescence spectroscopy, respectively. The anti-inflammatory effect was evaluated by means of paw edema induced by carrageenan or dextran, myeloperoxidase activity in paw tissue, and by measurement of leukocyte and neutrophil migration and cytokine quantification in a peritonitis model. The secondary structure of BtL is mostly composed of ß-strands and unordered conformation, and it is quite resistant to extremes of pH and temperature, preserving the exposure of Trp residues under these conditions. In an assessment of biological activities, groups of mice were subjected to pretreatment with BtL before the inflammatory stimulus. BtL had anti-inflammatory effects in the models tested, and hence may be considered a molecule with potential to be used in the pharmaceutical industry.
Assuntos
Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Lectinas/química , Lectinas/farmacologia , Rodófitas/química , Alga Marinha/química , Animais , Anti-Inflamatórios/uso terapêutico , Carragenina , Movimento Celular/efeitos dos fármacos , Dextranos , Edema/tratamento farmacológico , Edema/patologia , Feminino , Hemaglutinação/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Interleucina-1beta/biossíntese , Lectinas/isolamento & purificação , Lectinas/uso terapêutico , Camundongos , Peritonite/tratamento farmacológico , Peritonite/patologia , Peroxidase/antagonistas & inibidores , Peroxidase/metabolismo , Estrutura Secundária de Proteína , Coelhos , Espectrometria de Fluorescência , Temperatura , Fator de Necrose Tumoral alfa/biossínteseRESUMO
PURPOSE: To investigate the participation of cysteinyl leukotrienes in the pathophysiology of oral mucositis. METHODS: Oral mucositis was induced in hamsters using 5-fluorouracil (5-FU; 60 and 40 mg/kg; i.p., on days 1 and 2, respectively, and with excoriations in jugal mucosa on day 4). Montelukast (10, 20, or 40 mg/kg/d; gavage), MK886 (3 mg/kg/d, i.p.), or saline or celecoxib (7.5 mg/kg/d; i.p.) was administered 1 h prior to 5-FU and daily, until the fourth (MK886) or tenth day, when the animals were euthanized and their jugal mucosa was collected for macroscopic, histopathological, and immunohistochemical evaluation. RESULTS: Neither montelukast nor MK-886 prevented the oral mucositis induced by 5-FU, as observed by histopathological evaluation. In addition, we did not find significant differences in the expression of inducible nitric oxide synthase-2, cyclooxygenase-2, or interleukin (IL)-1ß between the experimental and control groups. However, we did observe a significant decrease in tumor necrosis factor (TNF)-α expression for all doses of montelukast; we also observed a significant decrease in IL-10 with 40 mg/kg/d and MK 886. CONCLUSIONS: Cysteinyl leukotrienes do not play an important role in experimental oral mucositis induced by 5-FU. There is a modulating action specifically on TNF-α.
Assuntos
Cisteína/metabolismo , Citocinas/metabolismo , Leucotrienos/metabolismo , Estomatite/prevenção & controle , Animais , Cricetinae , Modelos Animais de Doenças , Fluoruracila , Imuno-Histoquímica , Masculino , Estomatite/induzido quimicamente , Estomatite/metabolismoRESUMO
Purpose: To investigate the participation of cysteinyl leukotrienes in the pathophysiology of oral mucositis. Methods: Oral mucositis was induced in hamsters using 5-fluorouracil (5-FU; 60 and 40 mg/kg; i.p., on days 1 and 2, respectively, and with excoriations in jugal mucosa on day 4). Montelukast (10, 20, or 40 mg/kg/d; gavage), MK886 (3 mg/kg/d, i.p.), or saline or celecoxib (7.5 mg/kg/d; i.p.) was administered 1 h prior to 5-FU and daily, until the fourth (MK886) or tenth day, when the animals were euthanized and their jugal mucosa was collected for macroscopic, histopathological, and immunohistochemical evaluation. Results: Neither montelukast nor MK-886 prevented the oral mucositis induced by 5-FU, as observed by histopathological evaluation. In addition, we did not find significant differences in the expression of inducible nitric oxide synthase-2, cyclooxygenase-2, or interleukin (IL)-1 between the experimental and control groups. However, we did observe a significant decrease in tumor necrosis factor (TNF)- expression for all doses of montelukast; we also observed a significant decrease in IL-10 with 40 mg/kg/d and MK 886. Conclusions: Cysteinyl leukotrienes do not play an important role in experimental oral mucositis induced by 5-FU. There is a modulating action specifically on TNF-α.(AU)
Assuntos
Animais , Ratos , Estomatite/tratamento farmacológico , Cisteinildopa/administração & dosagem , Cisteinildopa/análiseRESUMO
Abstract Purpose: To investigate the participation of cysteinyl leukotrienes in the pathophysiology of oral mucositis. Methods: Oral mucositis was induced in hamsters using 5-fluorouracil (5-FU; 60 and 40 mg/kg; i.p., on days 1 and 2, respectively, and with excoriations in jugal mucosa on day 4). Montelukast (10, 20, or 40 mg/kg/d; gavage), MK886 (3 mg/kg/d, i.p.), or saline or celecoxib (7.5 mg/kg/d; i.p.) was administered 1 h prior to 5-FU and daily, until the fourth (MK886) or tenth day, when the animals were euthanized and their jugal mucosa was collected for macroscopic, histopathological, and immunohistochemical evaluation. Results: Neither montelukast nor MK-886 prevented the oral mucositis induced by 5-FU, as observed by histopathological evaluation. In addition, we did not find significant differences in the expression of inducible nitric oxide synthase-2, cyclooxygenase-2, or interleukin (IL)-1β between the experimental and control groups. However, we did observe a significant decrease in tumor necrosis factor (TNF)-α expression for all doses of montelukast; we also observed a significant decrease in IL-10 with 40 mg/kg/d and MK 886. Conclusions: Cysteinyl leukotrienes do not play an important role in experimental oral mucositis induced by 5-FU. There is a modulating action specifically on TNF-α.
Assuntos
Animais , Masculino , Estomatite/prevenção & controle , Leucotrienos/metabolismo , Citocinas/metabolismo , Cisteína/metabolismo , Estomatite/induzido quimicamente , Estomatite/metabolismo , Imuno-Histoquímica , Cricetinae , Modelos Animais de Doenças , FluoruracilaRESUMO
Intestinal mucositis (IM) is the critical side effect of irinotecan (CPT-11), which is the front-line drug used for the treatment of colorectal cancer. This study aimed to evaluate the effectiveness of latex proteins (LP) from Calotropis procera to prevent IM and diarrhea in animals. Swiss mice were treated daily with saline or LP (1, 5, or 50 mg/kg, i.v.) 24 h prior to CTP-11 (75 mg/kg/4 days, i.p) and for additional 6 days. Animal survival, body weight variation, and diarrhea were registered. After animal sacrifice (day 7 post first injection of CPT-11), intestinal samples were collected to study morphology and inflammatory parameters. Animals given LP exhibited improved parameters (survival, body weight, and absence of diarrhea) as compared with the CPT-11 control. The severity of IM observed in animals given CPT-11 was reduced in animals treated with LP. Treatment with LP also prevented the reduction in the villus/crypt ratio promoted by CPT-11. The rise in MPO activity and pro-inflammatory cytokines, over-contractility of the smooth muscle, and diarrhea were all abrogated in LP-treated mice. Markedly reduced immunostaining intensity for COX-2, TNF-α, IL-1ß, iNOS, and NF-κB was observed in the intestinal tissue of animals treated with LP. The side-effects of CPT-11 were eliminated by LP treatment in experimental animals and improved clinical parameters characteristic of IM All known biochemical pathogenesis. Copyright © 2016 John Wiley & Sons, Ltd.
Assuntos
Apocynaceae/química , Calotropis/química , Camptotecina/análogos & derivados , Neoplasias do Colo/tratamento farmacológico , Látex/farmacologia , Animais , Camptotecina/efeitos adversos , Neoplasias do Colo/patologia , Modelos Animais de Doenças , Irinotecano , Masculino , CamundongosRESUMO
OBJECTIVES: The aim of this study was to evaluate the anti-inflammatory effect of a sulphated polysaccharide fraction (PLS) extracted from the alga Hypnea musciformis and investigate the possible involvement of the nitric oxide (NO) pathway in this effect. METHODS: The anti-inflammatory activity of PLS was evaluated using inflammatory agents (carrageenan and dextran) to induce paw oedema and peritonitis in Swiss mice. Samples of paw tissue and peritoneal fluid were removed to determine myeloperoxidase (MPO) activity, NO3 /NO2 levels, and interleukin-1ß (IL-1ß) level. The involvement of NO in the modulation of neutrophil migration in carrageenan-induced paw oedema or peritonitis was also investigated. KEY FINDINGS: Compared with vehicle-treated mice, mice pretreated with PLS (10 mg/kg) inhibited carrageenan-induced and dextran-induced oedema; it also inhibited total and differential peritoneal leucocyte counts in a model of peritonitis. These PLS effects were reversed by l-arginine treatment and recovered with the administration of a NO synthase blocker (aminoguanidine). Furthermore, PLS reduced the MPO activity, decreased IL-1ß levels, and increased NO3 /NO2 levels in the peritoneal cavity. CONCLUSIONS: PLS reduced the inflammatory response by modulating neutrophil migration, which appeared to be dependent on the NO pathway.
Assuntos
Anti-Inflamatórios/uso terapêutico , Doenças do Sistema Imunitário/prevenção & controle , Inflamação/tratamento farmacológico , Transtornos Leucocíticos/prevenção & controle , Óxido Nítrico/metabolismo , Extratos Vegetais/uso terapêutico , Polissacarídeos/uso terapêutico , Rodófitas/química , Animais , Anti-Inflamatórios/farmacologia , Arginina/farmacologia , Carragenina , Dextranos , Edema/induzido quimicamente , Edema/tratamento farmacológico , Inibidores Enzimáticos/farmacologia , Guanidinas/farmacologia , Doenças do Sistema Imunitário/metabolismo , Inflamação/induzido quimicamente , Inflamação/imunologia , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Contagem de Leucócitos , Transtornos Leucocíticos/metabolismo , Masculino , Camundongos , Neutrófilos/efeitos dos fármacos , Óxido Nítrico Sintase/antagonistas & inibidores , Óxidos de Nitrogênio/metabolismo , Peritônio/efeitos dos fármacos , Peritônio/imunologia , Peritônio/metabolismo , Peritonite/induzido quimicamente , Peritonite/tratamento farmacológico , Peritonite/imunologia , Peritonite/metabolismo , Peroxidase/metabolismo , Fitoterapia , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Transdução de Sinais , Compostos de Enxofre/farmacologia , Compostos de Enxofre/uso terapêuticoRESUMO
Many algal species contain relatively high concentrations of polysaccharide substances, a number of which have been shown to have anti-inflammatory and/or immunomodulatory activity. In this study, we evaluated the anti-inflammatory and antinociceptive effects in mice of a sulfated polysaccharide fraction (PLS) extracted from the algae Gracilaria caudata. The antiinflammatory activity of PLS was evaluated using several inflammatory agents (carrageenan, dextran, bradykinin, and histamine) to induce paw edema and peritonitis in Swiss mice. Samples of the paw tissue and peritoneal fluid were removed to determine myeloperoxidase (MPO) activity or TNF-α and IL-1ß levels, respectively. Mechanical hypernociception was induced by subcutaneous injection of carrageenan into the plantar surface of the paw. Pretreatment of mice by intraperitoneal administration of PLS (2.5, 5, and 10 mg/kg) significantly and dose-dependently reduced carrageenan-induced paw edema (p < 0.05) compared to vehicle-treated mice. Similarly, PLS 10 mg/kg effectively inhibited edema induced by dextran and histamine; however, edema induced by bradykinin was unaffected by PLS. PLS 10 mg/kg inhibited total and differential peritoneal leukocyte counts following carrageenan-induced peritonitis. Furthermore, PLS reduced carrageenan-increased MPO activity in paws and reduced cytokine levels in the peritoneal cavity. Finally PLS pretreatment also reduced hypernociception 3-4 h after carrageenan. We conclude that PLS reduces the inflammatory response and hypernociception in mice by reducing neutrophil migration and cytokines concentration.
Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Gracilaria/química , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Rodófitas/química , Animais , Carragenina/efeitos adversos , Edema/induzido quimicamente , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Contagem de Leucócitos/métodos , Masculino , Camundongos , Peritonite/induzido quimicamente , Peroxidase/metabolismo , Extratos Vegetais/química , Polissacarídeos/química , Sulfatos/química , Sulfatos/farmacologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
This paper describes the purification and characterization of a new N-acetyl-d-glucosamine-specific lectin from Araucaria angustifolia (AaL) seeds (Araucariaceae) and its anti-inflammatory and antibacterial activities. AaL was purified using a combination of affinity chromatography on a chitin column and ion exchange chromatography on Sephacel-DEAE. The pure protein has 8.0kDa (SDS-PAGE) and specifically agglutinates rabbit erythrocytes, effect that was independent of the presence of divalent cations and was inhibited after incubation with glucose and N-acetyl-d-glucosamine. AaL showed antibacterial activity against Gram-negative and Gram-positive strains, shown by scanning electron microscopy. AaL, intravenously injected into rats, showed anti-inflammatory effect, via carbohydrate site interaction, in the models of paw edema and peritonitis. This lectin can be used as a tool for studying bacterial infections and inflammatory processes.