RESUMO
BACKGROUND AND AIM: Chemotherapy drugs that act via Toll-like receptors (TLRs) can exacerbate mucosal injury through the production of cytokines. Intestinal mucositis can activate TLR2 and TLR4, resulting in the activation of NF-κB. Intestinal mucositis characterized by intense inflammation is the main side effect associated with 5-fluorouracil (5-FU) treatment. Saccharomyces boulardii CNCM I-745 (S.b) is a probiotic yeast used in the treatment of gastrointestinal disorders. The main objective of the study was to evaluate the effect of S.b treatment on the Toll-like/MyD88/NF-κB/MAPK pathway activated during intestinal mucositis and in Caco-2 cells treated with 5-FU. METHODS: The mice were divided into three groups: saline (control), salineâ¯+â¯5-FU, and 5-FUâ¯+â¯S.b (1.6â¯×â¯1010 colony forming units/kg). After 3â¯days of S.b administration by gavage, the mice were euthanized and the jejunum and ileum were removed. In vitro, Caco2 cells were treated with 5-FU (1â¯mM) alone or in the presence of lipopolysaccharide (1â¯ng/ml). When indicated, cells were exposed to S.b. The jejunum/ileum samples and Caco2 cells were examined for the expression or concentration of the inflammatory components. RESULTS: Treatment with S.b modulated the expressions of TLR2, TLR4, MyD88, NF-κB, ERK1/2, phospho-p38, phospho-JNK, TNF-α, IL-1ß, and CXCL-1 in the jejunum/ileum and Caco2 cells following treatment with 5-FU. CONCLUSION: Toll-like/MyD88/NF-κB/MAPK pathway are activated during intestinal mucositis and their modulation by S.b suggests a novel and valuable therapeutic strategy for intestinal inflammation.
Assuntos
Citocinas/metabolismo , Fluoruracila/farmacologia , Mucosite/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Probióticos/farmacologia , Saccharomyces boulardii/metabolismo , Receptores Toll-Like/metabolismo , Animais , Células CACO-2 , Quimiocina CXCL1/genética , Quimiocina CXCL1/metabolismo , Citocinas/genética , Fluoruracila/efeitos adversos , Humanos , Íleo/metabolismo , Imuno-Histoquímica , Inflamação/metabolismo , Interleucina-1beta/genética , Janus Quinases/metabolismo , Jejuno/metabolismo , Lipopolissacarídeos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/genética , Masculino , Camundongos , Mucosite/tratamento farmacológico , Fosforilação , Probióticos/administração & dosagem , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Receptores Toll-Like/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
OBJECTIVE: The aim of this study was to investigate whether experimental periodontitis cause changes to the renal tissues and imbalance in oxidative stress in kidneys. METHODS: Twenty-two female Wistar rats were separated into two groups: control and periodontitis. We assessed the following parameters: gingival bleeding index (GBI), tooth mobility, gum malondialdehyde (MDA), myeloperoxidase (MPO) activity, probing pocket depth (PPD), alveolar bone loss (ABL) for periodontal tissues; histomorphometric measures associated with renal corpuscle and histopathological aspects (evaluation of brush border) for kidneys; as also blood and urine biomarkers. Finally, we evaluated renal oxidative stress through glutathione (GSH) and MDA respectively. RESULTS: With regard to renal histomorphometry, significant differences were observed in all parameters assessed. In relation periodic acid Schiff (PAS) staining, disruption was observed of brush border in the periodontitis group in the renal tubules in comparison with the control group. The periodontitis group presented significantly higher MDA and lower GSH concentrations in the kidneys compared with animals without periodontitis. CONCLUSION: The induced periodontitis caused histomorphometric changes in renal tissues as well as disruption of the brush border in renal tubules, alterations associated with increase in oxidative stress in kidneys. However, these alterations were not sufficient to cause differences in the renal function markers.
Assuntos
Nefropatias/etiologia , Peroxidação de Lipídeos/fisiologia , Estresse Oxidativo/fisiologia , Periodontite/complicações , Periodontite/metabolismo , Perda do Osso Alveolar , Animais , Biomarcadores/sangue , Biomarcadores/urina , Modelos Animais de Doenças , Feminino , Glutationa/análise , Nefropatias/patologia , Malondialdeído/análise , Perda da Inserção Periodontal , Índice Periodontal , Bolsa Periodontal , Periodonto , Peroxidase/metabolismo , Ratos , Ratos Wistar , Mobilidade DentáriaRESUMO
Long-term use nonsteroidal anti-inflammatory drug is associated with gastrointestinal (GI) lesion formation. The aim of this study was to investigate the protective activity of cashew gum (CG), a complex heteropolysaccharide extracted from Anacardium occidentale on naproxen (NAP)-induced GI damage. Male Wistar rats were pretreated with vehicle or CG (1, 3, 10, and 30 mg/kg, p.o.) twice daily for 2 days; after 1 h, NAP (80 mg/kg, p.o.) was administered. The rats were euthanized on the 2nd day of treatment, 4 h after NAP administration. Stomach lesions were measured using digital calipers. The medial small intestine was used for the evaluation of macroscopic lesion scores. Samples of the stomach and the intestine were used for histological evaluation, and assays for glutathione (GSH), malonyldialdehyde (MDA), and myeloperoxidase (MPO). Additional rats were used to measure gastric mucus and secretion. Pretreatment with CG reduced the macroscopic and microscopic damage induced by NAP. CG significantly attenuated NAP-induced alterations in MPO, GSH, and MDA levels. Furthermore, CG returned adherent mucus levels to normal values. These results suggest that CG has a protective effect against GI damage via mechanisms that involve the inhibition of inflammation and increasing the amount of adherent mucus in mucosa.
Assuntos
Anacardium , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/prevenção & controle , Naproxeno/efeitos adversos , Gomas Vegetais/uso terapêutico , Polissacarídeos/uso terapêutico , Animais , Gastroenteropatias/patologia , Masculino , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Gomas Vegetais/isolamento & purificação , Polissacarídeos/isolamento & purificação , Ratos , Ratos WistarRESUMO
The aim of this study was to investigate the antinociceptive and anti-inflammatory activities of epiisopiloturine (1), an imidazole alkaloid found in the leaves of Pilocarpus microphyllus. The anti-inflammatory activity of 1 was evaluated using several agents that induce paw edema and peritonitis in Swiss mice. Paw tissue and peritoneal fluid samples were obtained to determine myeloperoxidase (MPO) activity or tumor necrosis factor (TNF)-α and interleukin (IL)-1ß levels. The antinociceptive activity was evaluated by acetic acid-induced writhing, the hot plate test, and pain induction using formalin. Compared to vehicle treatment, pretreatment with 1 (0.1, 0.3, and 1 mg/kg, ip) of mice significantly reduced carrageenan-induced paw edema (p < 0.05). Furthermore, compound 1 at a dose of 1 mg/kg effectively inhibited edema induced by dextran sulfate, serotonin, and bradykinin, but had no effect on histamine-induced edema. The administration of 1 (1 mg/kg) following carrageenan-induced peritonitis reduced total and differential peritoneal leukocyte counts and also carrageenan-induced paw MPO activity and TNF-α and IL-1ß levels in the peritoneal cavity. Pretreatment with 1 also reduced acetic acid-induced writhing and inhibited the first and second phases of the formalin test, but did not alter response latency in the hot plate test. Pretreatment with naloxone reversed the antinociceptive effect of 1.
Assuntos
4-Butirolactona/análogos & derivados , Alcaloides/farmacologia , Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Imidazóis/farmacologia , Pilocarpus/química , 4-Butirolactona/química , 4-Butirolactona/farmacologia , Alcaloides/sangue , Alcaloides/química , Analgésicos/sangue , Analgésicos/química , Animais , Anti-Inflamatórios/sangue , Anti-Inflamatórios/química , Brasil , Imidazóis/química , Masculino , Camundongos , Estrutura Molecular , Neutrófilos/efeitos dos fármacos , Medição da Dor , Peroxidase/sangue , Peroxidase/metabolismoRESUMO
Parotoid glands of amphibians are known for the production of several biologically active compounds having pharmacological and toxic effects in mammals. In the present work, a protein fraction obtained from Rhinella schneideri parotoid gland (RsPP) was characterized to study its biological and toxic effects. Rhinella schneideri parotoid secretion is composed of up to 30% (w/w) of soluble proteins. Tandem mass spectrometric analysis of the RsPP identified 104 proteins, including actin, beta-actin, ribosomal proteins, catalase, galectin, and uncharacterized proteins; however, no peptidases were found, and this result was reinforced by the absence of proteolytic activity. In addition, RsPP did not exhibit pro-coagulant or antibacterial effects. However, pretreatment of mice with different doses of RsPP intraperitoneally inhibited carrageenan-induced paw edema and increased tissue myeloperoxidase activity. RsPP also reduced interleukin 1ß levels in the peritoneal cavities and cell migration in the peritoneal cavities of an animal model of carrageenan-induced peritonitis. Subchronic treatment of animals with RsPP for 7 consecutive days did not alter the serum biochemical, renal, or liver parameters. However, a significant reduction in blood leukocyte count was observed. Our results showed that R. schneideri parotoid secretion contains proteins with anti-inflammatory and slight toxic effects.
Assuntos
Proteínas de Anfíbios/farmacologia , Venenos de Anfíbios/farmacologia , Anti-Inflamatórios/farmacologia , Edema/tratamento farmacológico , Peritonite/tratamento farmacológico , Proteínas de Anfíbios/análise , Proteínas de Anfíbios/toxicidade , Venenos de Anfíbios/química , Venenos de Anfíbios/toxicidade , Animais , Bufonidae/metabolismo , Edema/metabolismo , Extremidades , Feminino , Contagem de Leucócitos , Masculino , Camundongos , Peroxidase/efeitos dos fármacos , Espectrometria de Massas em TandemRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Anacardium occidentale L. (Anacardiaceae) is commonly known as the cashew tree. It is native to tropical America and extracts of the leaves, bark, roots, chestnut net and exudate have been traditionally used in northeast Brazil for the treatment of various diseases. The exudate of the cashew tree (cashew gum) has been exploited by locals since ancient times for multiple applications, including the treatment of diarrheal diseases. AIM OF THE STUDY: The primary aim of the present study is to evaluate the antidiarrheal activity of cashew gum (CG), a complex heteropolysaccharide from the exudate of the cashew tree, using various models. MATERIALS AND METHODS: The antidiarrheal activity of cashew gum (CG) against acute diarrhea was investigated using the castor oil-induced diarrhea model. The effects of CG on gastrointestinal transit and castor oil- and PGE2- induced enteropooling were also examined in rodents. In addition, the effect of CG against secretory diarrhea was investigated using a model of fluid secretion in cholera toxin-treated intestinal closed loops in live mice. RESULTS: Cashew gum (30, 60, and 90 mg/kg, p.o.) showed a significant (P<0.05-0.01) antidiarrheal effect in rats with castor oil-induced diarrhea, inhibiting the total amount of stool and diarrheal stools. The 60 mg/kg dose of CG exhibited excellent antidiarrheal activity and significantly reduced the severity of diarrhea (diarrhea scores) in rats. CG (60 mg/kg) significantly (P<0.05) decreased the volume of castor oil- and PGE2-induced intestinal fluid secretion (enteropooling). In addition, similar to loperamide (standard drug, 5 mg/kg, p.o.), CG treatment reduced the distance traveled by a charcoal meal in the 30-min gastrointestinal transit model by interacting with opioid receptors. In cholera toxin-induced secretory diarrhea, CG (60 mg/kg) significantly inhibited the intestinal fluid secretion and decreased Cl(-) ion loss in the cholera toxin(-)treated isolated loops model of live mice by competitively binding to cholera toxin-GM1 receptors. CONCLUSIONS: In conclusion, our results indicate that a complex heteropolysaccharide extracted from the exudate of A. occidentale L. has antidiarrheal activity in acute, inflammatory, and secretory diarrhea models, which could justify its traditional use in the treatment of diarrhea in northeast Brazil. The antidiarrheal activity might be explained by the capacity of CG to inhibit gastrointestinal motility and thereby reduce the accumulation of intestinal fluid and the secretion of water and chloride ions in the lumen of the intestine.
Assuntos
Anacardium , Antidiarreicos/uso terapêutico , Diarreia/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Gomas Vegetais/uso terapêutico , Animais , Antidiarreicos/isolamento & purificação , Óleo de Rícino/toxicidade , Diarreia/induzido quimicamente , Diarreia/fisiopatologia , Feminino , Masculino , Camundongos , Extratos Vegetais/isolamento & purificação , Gomas Vegetais/isolamento & purificação , Polissacarídeos/isolamento & purificação , Polissacarídeos/uso terapêutico , Ratos , Ratos WistarRESUMO
Inflammation is a local tissue response to attacks characterized by vascular and cellular events, including intense oxidative stress. Riparin A, a compound obtained from Aniba riparia, has been shown to have antioxidant activity and cytotoxicity in vitro. This study was aimed at evaluating the anti-inflammatory effect of riparin A against acute inflammation. The results of our evaluations in various experimental models indicated that riparin A reduced paw edema induced by carrageenan, compound 48/80, histamine, and serotonin. Furthermore, it decreased leukocyte and neutrophil counts, myeloperoxidase activity, thiobarbituric acid reactive substance (TBARS) levels, and cytokine (tumor necrosis factor-α and interleukin-1ß) levels increased by carrageenan-induced peritonitis, and reversed glutathione levels. Riparin A also reduced carrageenan-induced adhesion and rolling of leukocytes on epithelial cells and did not produce gastric-damage as compared with indomethacin. In conclusion, the data show that riparin A reduces inflammatory response by inhibiting vascular and cellular events, modulating neutrophil migration, inhibiting proinflammatory cytokine production, and reducing oxidative stress.
Assuntos
Anti-Inflamatórios/uso terapêutico , Benzamidas/uso terapêutico , Carragenina/efeitos adversos , Edema/tratamento farmacológico , Doenças do Sistema Imunitário/tratamento farmacológico , Transtornos Leucocíticos/tratamento farmacológico , Neutrófilos/efeitos dos fármacos , Peritonite/tratamento farmacológico , Fenetilaminas/uso terapêutico , Animais , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/isolamento & purificação , Antioxidantes/uso terapêutico , Benzamidas/isolamento & purificação , Carragenina/imunologia , Adesão Celular/efeitos dos fármacos , Citocinas/imunologia , Edema/induzido quimicamente , Edema/imunologia , Edema/patologia , Extremidades/patologia , Doenças do Sistema Imunitário/induzido quimicamente , Doenças do Sistema Imunitário/imunologia , Doenças do Sistema Imunitário/patologia , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/patologia , Lauraceae/química , Transtornos Leucocíticos/induzido quimicamente , Transtornos Leucocíticos/imunologia , Transtornos Leucocíticos/patologia , Migração e Rolagem de Leucócitos/efeitos dos fármacos , Masculino , Camundongos , Neutrófilos/imunologia , Neutrófilos/patologia , Estresse Oxidativo/efeitos dos fármacos , Peritonite/induzido quimicamente , Peritonite/imunologia , Peritonite/patologia , Peroxidase/imunologia , Fenetilaminas/isolamento & purificaçãoRESUMO
OBJECTIVES: The aim of the study was to investigate the anti-inflammatory, antioxidant and antinociceptive actions of PFPe, a polysaccharide fraction isolated from the dried fruit of the Passiflora edulis. METHODS: Animals were pretreated with PFPe (0.3, 1 or 3 mg/kg, i.p.) 1 h before induction of paw oedema by carrageenan, histamine, serotonin, compound 48/80 or prostaglandin E2 (PGE2). Neutrophil migration and vascular permeability were measured after carrageenan injection into the peritoneum, and the action of the PFPe on the tumour necrosis factor-alpha, interleukin-1 beta (IL-1ß), myeloperoxidase (MPO), glutathione (GSH) and malondialdehyde (MDA) levels was also evaluated. To assay nociception, we examined acetic acid-induced writhing, formalin-induced paw licking and response latency in the hot plate test. KEY FINDINGS: Pretreatment with PFPe significantly inhibited carrageenan-induced paw oedema. PFPe also reduced paw oedema induced by compound 48/80, histamine, serotonin, and PGE2 and compound 48/80-induced vascular permeability. In addition, PFPe significantly reduced the MPO activity, MDA and GSH concentrations, and IL-1ß level. In the nociception tests, PFPe reduced acetic acid-induced writhing and formalin-induced paw licking and did not increase the response latency time. CONCLUSIONS: Our results suggest that PFPe administration reduces the inflammatory response by modulation of the liberation or synthesis of histamine and serotonin, by reduction of neutrophil migration, IL-1ß levels, and oxidative stress and nociception.
Assuntos
Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Passiflora/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Analgésicos/química , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/química , Permeabilidade Capilar/efeitos dos fármacos , Carragenina/farmacologia , Dinoprostona/metabolismo , Edema/tratamento farmacológico , Edema/metabolismo , Glutationa/metabolismo , Histamina/metabolismo , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Medição da Dor/métodos , Peroxidase/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Serotonina/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Studies have shown that diterpenes have anti-inflammatory and redox-protective pharmacological activities. The present study aimed to investigate the anti-inflammatory properties of phytol, a diterpene alcohol, in a mouse model of acute inflammation, and phytol effect on leukocyte recruitment, cytokines levels, and oxidative stress. The anti-inflammatory activities of phytol were assessed by measuring paw edema induced by different inflammatory agents (e.g., λ-carrageenan, compound 48/80, histamine, serotonin, bradykinin, and prostaglandin E2 [PGE2 ]), myeloperoxidase (MPO) activity, peritonitis model and cytokine levels. Further, oxidative stress was evaluated by determining glutathione (GSH) levels and malondialdehyde (MDA) concentration. The results showed that phytol (7.5, 25, 50, and 75 mg/kg) significantly reduced carrageenan-induced paw edema, in a dose-dependent manner. In addition, phytol (75 mg/kg) inhibited compound 48/80-, histamine-, serotonin-, bradykinin- and PGE2 -induced paw edema. It also inhibited the recruitment of total leukocytes and neutrophils; decreased MPO activity, tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) levels, and MDA concentration; and increased GSH levels during carrageenan-induced acute inflammation. These results suggest that phytol attenuates the inflammatory response by inhibiting neutrophil migration that is partly caused by reduction in IL-1ß and TNF-α levels and oxidative stress.
Assuntos
Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Fitol/farmacologia , Animais , Anti-Inflamatórios/administração & dosagem , Citocinas/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Edema/tratamento farmacológico , Edema/patologia , Glutationa/metabolismo , Inflamação/patologia , Interleucina-1beta/metabolismo , Leucócitos/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Neutrófilos/metabolismo , Peroxidase/metabolismo , Fitol/administração & dosagem , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVES: The aim of this study was to evaluate the protective effect of the sulfated-polysaccharide (PLS) fraction extracted from the seaweed Gracilaria birdiae in rats with trinitrobenzenesulfonic acid (TNBS)-induced colitis. METHODS: In the experiments involving TNBS-induced colitis, rats were pretreated with polysaccharide extracted from G. birdiae (PLS: 30, 60 and 90 mg/kg, 500 µL p.o.) or dexamethasone (control group: 1 mg/kg) once daily for 3 days starting before TNBS instillation (day 1). The rats were killed on the third day, the portion of distal colon was excised and washed with 0.9% saline and pinned onto a wax block for the evaluation of macroscopic scores. Samples of the intestinal tissue were used for histological evaluation and assays for glutathione (GSH) levels, malonyldialdehyde (MDA) concentration, myeloperoxidase (MPO) activity, nitrate and nitrite (NO3 /NO2 ) concentration and cytokines levels. KEY FINDINGS: PLS treatment reduced the macroscopic and microscopic TNBS-induced intestinal damage. Additionally, it avoided the consumption of GSH, decreased pro-inflammatory cytokine levels, MDA and NO3 /NO2 concentrations and diminished the MPO activity. CONCLUSIONS: Our results suggest that the PLS fraction has a protective effect against intestinal damage through mechanisms that involve the inhibition of inflammatory cell infiltration, cytokine releasing and lipid peroxidation.
Assuntos
Colite/induzido quimicamente , Colite/tratamento farmacológico , Colo/efeitos dos fármacos , Gracilaria/química , Polissacarídeos/farmacologia , Rodófitas/química , Ácido Trinitrobenzenossulfônico/farmacologia , Animais , Citocinas/metabolismo , Dexametasona/farmacologia , Glutationa/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Nitratos/metabolismo , Nitritos/metabolismo , Peroxidase/metabolismo , Polissacarídeos/química , Ratos , Ratos WistarRESUMO
The sulfated polysaccharide (PLS) fraction of Agardhiella ramosissima was characterized by microanalysis, infrared spectroscopy, NMR and gas-liquid-chromatography-mass-spectrometry. The main constituent of PLS was the ι carrageenan. The monosaccharide composition of the PLS showed galactose, 3,6-anhydrogalactose and 6-O-methylgalactose. The PLS (30 mg kg(-1)) significantly reduced the paw oedema induced by carrageenan, dextran, histamine and serotonin and also was able to significantly inhibit leucocyte migration into the peritoneal cavity and decrease the concentration of myeloperoxidase (MPO) in paw tissue. In the antinociceptive tests, the pre-treatment with PLS reduced the number of writhes, the licking time but did not increase the latency time of response. This study demonstrates for the first time the anti-inflammatory and anti-nociceptive effects of PLS from A. ramosissima. Thus, we concluded that PLS could be a new natural tool in pain and acute inflammatory conditions.
Assuntos
Anti-Inflamatórios/farmacologia , Edema/tratamento farmacológico , Inflamação/tratamento farmacológico , Dor/tratamento farmacológico , Extratos Vegetais/química , Polissacarídeos/farmacologia , Rodófitas/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Carragenina , Movimento Celular/efeitos dos fármacos , Dextranos , Edema/induzido quimicamente , Edema/fisiopatologia , Galactose/análogos & derivados , Galactose/química , Membro Posterior , Histamina , Inflamação/induzido quimicamente , Inflamação/fisiopatologia , Masculino , Metilgalactosídeos/química , Camundongos , Nociceptividade/efeitos dos fármacos , Nociceptividade/fisiologia , Dor/induzido quimicamente , Dor/fisiopatologia , Peroxidase/antagonistas & inibidores , Peroxidase/metabolismo , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Serotonina , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Our objective was to evaluate the role of soluble guanylate cyclase (sGC) activation in the gastroprotective effect of the HO-1/CO pathway against alendronate-induced gastric damage in rats. Rats were pretreated, once daily for 4 days, with saline, hemin (HO-1 inducer), or dimanganese decacarbonyl (DMDC, CO donor). Another group received zinc protoporphyrin IX (ZnPP IX, HO-1 antagonist) 1 h before hemin treatment or sGC inhibitor (ODQ) 30 min before hemin and DMDC treatment. After 30 min, gastric damage was induced by alendronate (30 mg/kg) by gavage. On the last day of treatment, 4 h after alendronate administration, the animals were killed. Gastric lesions were measured using a computer planimetry program, and gastric corpus pieces were assayed for malondialdehyde (MDA), glutathione (GSH), pro-inflammatory cytokines (tumor necrosis factor [TNF]-α and interleukin [IL]-1ß), myeloperoxidase (MPO), or bilirubin. Another group was used to measure gastric mucus. HO-1 expression was determined after saline or alendronate administration by immunohistochemistry. Alendronate induced gastric damage, produced neutrophil accumulation, increased MDA levels and MPO activity, and reduced GSH and mucus in the gastric tissue. Alendronate also increased HO-1 immunoreactivity and the level of bilirubin in gastric mucosa. Pretreatment with hemin or DMDC reduced neutrophil infiltration and TNF-α, IL-1ß, and MDA formation, and increased the levels of GSH and mucus in the gastric tissue. ODQ completely abolished the gastroprotective effect of hemin and DMDC and increased alendronate gastric damage. Our results suggest that the HO-1/CO pathway plays a protective role against alendronate-induced gastric damage through mechanisms that can be dependent on sGC activation.
Assuntos
Alendronato/efeitos adversos , Monóxido de Carbono/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Guanilato Ciclase/metabolismo , Heme Oxigenase-1/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Animais , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Masculino , Ratos , Ratos Wistar , Guanilil Ciclase SolúvelRESUMO
AbstractSome publications have described the pharmacological properties of latices proteins. Thus, in the present study proteins from Plumeria pudica Jacq., Apocynaceae, latex were evaluated for anti-inflammatory and antinociceptive activities. Obtained data showed that an intraperitoneal administration of different doses of latex was able to reduce the paw edema induced by carrageenan in a dose-dependent manner (better dose 40 mg/kg; 72.7% inhibition at 3rd and 78.7% at 4th hour) and the edema induced by dextran (40 mg/kg; 51.5% inhibition at 30 min and 93.0% at 1st hour). Inhibition of edema induced by carrageenan was accompanied by a reduction of myeloperoxidase activity. Pre-treating animals with latex (40 mg/kg) also inhibited the paw edema induced by histamine, serotonin, bradykinin, prostaglandin E2, compound 48/80. Additionally, the latex (40 mg/kg) reduced the leukocyte peritoneal migration induced by carrageenan and this event was followed by reduction of IL-1β and TNF-α in peritoneal fluid. The latex-treatment (40 mg/kg) reduced the animal abdominal constrictions induced by acetic acid and the first phase on paw licking model induced by formalin. When latex was treated with heat (at 100 °C for 30 min), anti-edematogenic and myeloperoxidase activities were significantly reduced, indicating the involvement of heat-sensitive proteins on anti-inflammatory effect. Our results evidence that latex fluids are a source of proteins with pharmacological properties.
RESUMO
Seaweeds are the most abundant source of polysaccharides such as alginates and agar, as well as carrageenans. This study aimed to investigate the gastroprotective activity and the mechanism underlying this activity of a sulfated-polysaccharide fraction extracted from the algae Hypnea musciformis (Wulfen) J.V. Lamour. (Gigartinales-Rhodophyta). Mice were treated with sulfated-polysaccharide fraction (3, 10, 30, and 90 mg/kg, p.o.) and, after 30 min, they were administered 50% ethanol (0.5 mL/25 g, p.o.). After 1 h, gastric damage was measured using a planimeter. In addition, samples of the stomach tissue were obtained for histopathological examination and for assays to determine the glutathione and malondialdehyde levels. Other groups of mice were pretreated with N G-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg, i.p.), aminoguanidine (100 mg/kg, i.p.), or glibenclamide (10 mg/kg, i.p.). After 30 min to the aminoguanidine group and 1 h to the other groups, sulfated-polysaccharide fraction (30 mg/kg, p.o.) was administered and gastric damage was induced as described above. Sulfated-polysaccharide fraction prevented ethanol-induced gastric injury in a dose-dependent manner. However, treatment with L-NAME or glibenclamide reversed this gastroprotective effect. Administration of aminoguanidine did not influence the effect of sulfated-polysaccharide fraction. Our results suggest that sulfated-polysaccharide fraction exerts a protective effect against ethanol-induced gastric damage via activation of the NO/K ATP pathway.