RESUMO
Hydrogen sulfide (H2S) is a signaling molecule in the gastrointestinal tract. H2S production can derive from d-cysteine via various pathways, thus pointing to a new therapeutic approach: delivery of H2S to specific tissues. This study was designed to evaluate the concentration and effects of H2S (generated by d-amino acid oxidase [DAO] from d-cysteine) in the gastric mucosa and the protective effects against ethanol-induced lesions in mice. Mice were treated with l-cysteine or d-cysteine (100 mg/kg per os). Other groups received oral l-propargylglycine (cystathionine γ-lyase inhibitor, 100 mg/kg) or indole-2-carboxylate (DAO inhibitor), and 30 min later, received d- or l-cysteine. After 30 min, 50% ethanol (2.5 mL/kg, per os) was administered. After 1 h, the mice were euthanized and their stomachs excised and analyzed. Pretreatment with either l-cysteine or d-cysteine significantly reduced ethanol-induced lesions. Pretreatment of d-cysteine- or l-cysteine-treated groups with indole-2-carboxylate reversed the gastroprotective effects of d-cysteine but not l-cysteine. Histological analysis revealed that pretreatment with d-cysteine decreased hemorrhagic damage, edema, and the loss of the epithelium, whereas the administration of indole-2-carboxylate reversed these effects. d-Cysteine also reduced malondialdehyde levels but maintained the levels of reduced glutathione. Furthermore, pretreatment with d-cysteine increased the synthesis of H2S. Thus, an H2S-generating pathway (involving d-cysteine and DAO) is present in the gastric mucosa and protects this tissue from ethanol-induced damage by decreasing direct oxidative damage.
Assuntos
Antioxidantes/farmacologia , Cisteína/farmacologia , D-Aminoácido Oxidase/metabolismo , Mucosa Gástrica , Sulfeto de Hidrogênio/metabolismo , Animais , Etanol/efeitos adversos , Feminino , Mucosa Gástrica/química , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Glutationa/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Gastropatias/induzido quimicamente , Gastropatias/metabolismoRESUMO
Inflammation is a protective reaction of the microcirculation. However, sustained inflammation can lead to undesired effects. Thuja occidentalis Linn has many pharmacological properties but has no anti-inflammatory activity described. Thus, this study aims evaluating the anti-inflammatory activity of the aqueous extract (AE) and the polysaccharide fraction (PLS) of T. occidentalis L. in mice. The results of our evaluations in various experimental models indicated that AE and PLS (3, 10, and 30mg/kg, i.p.) reduced (pË0.05) paw edema induced by carrageenan, dextran sulfate (DEX), compound 48/80, serotonin (5-HT), bradykinin (BK), histamine (HIST), and prostaglandin E2 (PGE2). Furthermore, it inhibited neutrophils recruitment; decreased MPO activity, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels, vascular permeability, nitrite concentration, and MDA concentration; and maintained the GSH levels in the peritoneal exudate. The AE and PLS reduced neutrophil infiltration and cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) immunostaining in paw tissue. Treatment with the AE and PLS (300mg/kg) did not induce gastric toxicity. In conclusion, these results show that the AE and PLS reduced the inflammatory response by inhibiting vascular and cellular events, inhibiting pro-inflammatory cytokine production, and reducing oxidative stress. Furthermore, they did not induce gastric toxicity at high doses.
Assuntos
Anti-Inflamatórios/farmacologia , Polissacarídeos/farmacologia , Thuja/química , Água/química , Animais , Anti-Inflamatórios/uso terapêutico , Permeabilidade Capilar/efeitos dos fármacos , Edema/tratamento farmacológico , Edema/metabolismo , Glutationa/metabolismo , Interleucina-6/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Óxido Nítrico/biossíntese , Cavidade Peritoneal , Peritonite/tratamento farmacológico , Peroxidase/metabolismo , Polissacarídeos/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismoRESUMO
This study investigated the anti-inflammatory activity of the extract (LEG) and purified (LPG) lycopene from guava (Psidium guajava L.), as well as some mechanisms possibly involved in this effect. The anti-inflammatory activity was initially assessed using paw edema induced by Carrageenan, Dextran, Compound 48/80, Histamine and Prostaglandin E2 in Swiss mice. A peritonitis model was used to evaluate neutrophil migration, the activity of myeloperoxidase (MPO) and reduced glutathione (GSH) concentration; while the effect on the expression of iNOS, COX-2 and NF-κB, was assessed by immunohistochemistry analysis. Results showed that oral and intraperitoneal administration of LEG and LPG inhibited inflammation caused by carrageenan. LPG (12.5mg/kg p.o.) significantly inhibited the edema formation induced by different phlogistic agents and immunostaining for iNOS, COX-2 and NF-κB. Leukocytes migration in paw tissue and peritoneal cavity was reduced, as well as MPO concentration, whereas GSH levels increased. Thus, lycopene-rich extract from red guava has beneficial effect on acute inflammation, offering protection against the consequences of oxidative stress by downregulating inflammatory mediators and inhibiting gene expression involved in inflammation.
Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Edema/prevenção & controle , Inflamação/prevenção & controle , Leucócitos/efeitos dos fármacos , Peritonite/prevenção & controle , Extratos Vegetais/farmacologia , Psidium , Animais , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/isolamento & purificação , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Edema/imunologia , Edema/metabolismo , Feminino , Frutas , Glutationa/metabolismo , Inflamação/imunologia , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Leucócitos/imunologia , Leucócitos/metabolismo , Masculino , Camundongos , NF-kappa B/metabolismo , Infiltração de Neutrófilos/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peritonite/imunologia , Peritonite/metabolismo , Peroxidase/metabolismo , Extratos Vegetais/isolamento & purificação , Psidium/químicaRESUMO
Seaweeds are sources of diverse bioactive compounds, such as sulphated polysaccharides. This study was designed to evaluate the chemical composition and anti-diarrheal activity of a fraction of sulphated polysaccharide (PLS) obtained from the red seaweed Hypnea musciformis in different animal models, and to elucidate the underlying mechanisms. PLS was obtained by aqueous extraction, with a yield of 31.8% of the seaweed dry weight. The total carbohydrate content accounted for 99% of the sample. The sulfate content of the polysaccharide was 5.08% and the percentage of carbon was 25.98%. Pretreatment with all doses of PLS inhibited castor oil-induced diarrhea, with reduction of the total amount of stool, diarrheal stools, and the severity of diarrhea. PLS (90 mg/Kg) decreased castor oil- and PGE2-induced enteropooling. In addition, PLS (90 mg/Kg) increased the Na(+)/K(+)-ATPase activity in the small intestine and reduced gastrointestinal transit, possibly via activation of cholinergic receptors. Interestingly, the cholera toxin-induced fluid secretion and Cl(-) ion levels decreased in the intestinal contents of the animals pretreated with PLS (90 mg/kg), probably via reduction of toxin-GM1 receptor binding. In conclusion, PLS exerts anti-diarrheal activity by increasing Na(+)/K(+)-ATPase activity, inhibiting gastrointestinal motility, and blocking the toxin-GM1 receptor binding.
Assuntos
Diarreia/tratamento farmacológico , Polissacarídeos/química , Polissacarídeos/farmacologia , Rodófitas/química , Sulfatos/química , Animais , Óleo de Rícino/efeitos adversos , Toxina da Cólera/toxicidade , Diarreia/induzido quimicamente , Diarreia/metabolismo , Diarreia/fisiopatologia , Feminino , Trânsito Gastrointestinal/efeitos dos fármacos , Absorção Intestinal/efeitos dos fármacos , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Intestino Delgado/fisiopatologia , Masculino , Camundongos , Antagonistas de Entorpecentes/farmacologia , Polissacarídeos/uso terapêutico , Ratos , Receptores de Superfície Celular/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismoRESUMO
The angiotensin (Ang) II converting enzyme (ACE II) pathway has recently been shown to be associated with several beneficial effects in various organisms, including gastroprotection. ACE II is responsible for converting Ang II into an active peptide, Ang-(1-7), which in turn binds the Mas receptor. Recent studies have shown that diminazene aceturate (Dize) a trypanocidal used in animals, activates ACE II. Thus, in this study, we aimed to evaluate the gastroprotective effects of Dize via the ACE II/Ang-(1-7)/Mas receptor pathway against gastric lesions induced by ethanol and acetic acid in mice. The results showed that Dize could promote gastric protection via several mechanisms, including increased levels of antioxidants and anti-inflammatory factors (e.g., decreasing tumor necrosis factor and interleukin-6 expression and reducing myeloperoxidase activity), maturation of collagen fibers, and promotion of re-epithelialization and regeneration of gastric tissue in different injury models. Thus, Dize represents a novel potential gastroprotective agent.