RESUMO
Lupeol (1) was isolated from hexane branch extract of Maytenus salicifolia and the Lupeol stearate (2), Lupeol palmitate (3), Lupeol myristate (4), Lupeol laurate (5) and Lupeol caprylate (6) were obtained reacting 1 with an adequate carboxylic acid. Swiss mice were treated with vehicle, carbenoxolone or Lupeol esters before administration of ethanol/HCl or indomethacin. Additionally, the involvement of nitric oxide (NO), sulfhydryl compounds (NP-SH), α-2 adrenergic receptors (α2-AR) and prostaglandins (PGE) in antiulcer effects was investigated using appropriate inhibitors or antagonist. Oxidative and inflammatory parameters were measured after euthanasia and anti-secretory effects was evaluated in pylorus-ligated rats. Ethanol/HCl ulcerated the gastric mucosa by 64.45 ± 6.58 mm2, which the oral treatment with 1, 4 and 6 (10 mg/kg), and 3 and 5 (30 mg/kg) reduced the lesion area. Interestingly, 2 reduced the gastric ulcer by oral route in a potent and dose-dependent manner (ED50 = 0.40 mg/kg), which was accompanied by the increase in reduced glutathione levels and by the reduction of lipids peroxidation and myeloperoxidase and superoxide dismutase activities. Moreover, 2 (0.1 mg/kg) also prevented the ulcerogenesis by intraperitoneal route. The participation of NO, NP-SH, α2-AR and PGE in 2-mediated gastroprotection was confirmed. In indomethacin-induced ulcer, 2 (1 mg/kg, p.o) also reduced the ulcer area and increased the PGE2 levels. However, 2 did not alter the gastric acid secretion. Therefore, these findings indicate that the obtention of 2 potentiated the antiulcer activity of 1 and that this compound can elicit gastroprotective action due a diversified mode of action.
Assuntos
Antiulcerosos/farmacologia , Triterpenos Pentacíclicos/farmacologia , Úlcera Gástrica/prevenção & controle , Animais , Antiulcerosos/administração & dosagem , Antiulcerosos/química , Modelos Animais de Doenças , Esterificação , Etanol/toxicidade , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Ácido Clorídrico/toxicidade , Indometacina/toxicidade , Camundongos , NG-Nitroarginina Metil Éster/metabolismo , Óxido Nítrico/metabolismo , Triterpenos Pentacíclicos/administração & dosagem , Triterpenos Pentacíclicos/química , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Relação Estrutura-AtividadeRESUMO
This in vitro study evaluated the impact of initial erosion on the susceptibility of enamel to further erosive challenge. Thirty bovine enamel blocks were selected by surface hardness and randomized into two groups (n = 15): GC- group composed by enamel blocks without erosion lesion and GT- group composed by enamel blocks with initial erosion lesion. The baseline profile of each block was determined using the profilometer. The initial erosion was produced by immersing the blocks into HCl 0.01 M, pH 2.3 for 30 seconds, under stirring. The erosive cycling consisted of blocks immersion in hydrochloric acid (0.01 M, pH 2.3) for 2 minutes, followed by immersion in artificial saliva for 120 minutes. This procedure was repeated 4 times a day for 5 days, and the blocks were kept in artificial saliva overnight. After erosive cycling, final profile measurement was performed. Profilometry measured the enamel loss by the superposition of initial and final profiles. Data were analyzed by t-test (p<0.05). The result showed no statistically significant difference between groups (GS = 14.60±2.86 and GE = .14.69±2.21 µm). The presence of initial erosion on bovine dental enamel does not enhance its susceptibility to new erosive challenges.
Assuntos
Esmalte Dentário/efeitos dos fármacos , Erosão Dentária/patologia , Animais , Bovinos , Esmalte Dentário/patologia , Ácido Clorídrico/farmacologia , Ácido Clorídrico/toxicidade , Erosão Dentária/etiologiaRESUMO
REASONS FOR PERFORMING STUDY: Treatment of metabolic acidosis using sodium bicarbonate solutions is safe when blood gas analysis is available. The evidence that solutions containing metabolisable buffers can be used as an alternative for treatment of metabolic acidosis in horses is of practical interest. OBJECTIVES: To investigate the safety and efficacy of a polyionic solution containing 84 mEq/l of lactate (L84) for the correction of induced hyperchloraemic metabolic acidosis. STUDY DESIGN: Non-randomised crossover design. METHODS: Five healthy, adult, crossbred horses were used. A solution containing 100 mmol/l of HCl was infused intravenously (100 ml/kg bwt) for 5 h to induce metabolic acidosis. Metabolic acidosis was induced in each horse twice, with a minimum 15-day interval after recovery from the first induction: the first time no treatment was administered (control group) and the second time horses were treated with an intravenous infusion of L84 solution, 100 ml/kg bwt for 5 h, beginning 3 h after the end of HCl infusion. Venous blood samples were taken at 0, 2.5, 5, 8, 10.5, 13, 24 and 48 h; and urine at 0, 5, 8 and 13 h. Laboratory data included pH (blood and urine), PCO2 , HCO3- , base excess, total plasma protein concentration, l-lactate, Na+ , K+ , Cl- , strong ion difference (SID4 ), anion gap, change in plasma volume and fractional excretions of Na+ , K+ and Cl- . Effects of time and treatment were tested by 2-way repeated measures ANOVA. RESULTS: Severe hyperchloraemic metabolic acidosis was induced. In the untreated horses, correction of the imbalance occurred gradually, and mild acidosis was still present at 48 h. In horses treated with the L84 solution, acidosis was corrected by the end of the infusion. There were no adverse effects with the administration of the L84 solution. CONCLUSIONS: A polyionic solution containing 84 mEq/l of lactate effectively corrected induced metabolic acidosis in horses within 5 h.
Assuntos
Acidose/veterinária , Eletrólitos/farmacologia , Doenças dos Cavalos/induzido quimicamente , Ácido Clorídrico/toxicidade , Ácido Láctico/uso terapêutico , Desequilíbrio Ácido-Base , Acidose/induzido quimicamente , Acidose/tratamento farmacológico , Animais , Estudos Cross-Over , Eletrólitos/administração & dosagem , Feminino , Doenças dos Cavalos/tratamento farmacológico , Cavalos , Injeções Intravenosas , Ácido Láctico/administração & dosagem , MasculinoRESUMO
Acute lung injury (ALI) is characterized by alveolar edema and uncontrolled neutrophil migration to the lung, and no specific therapy is still available. Ellagic acid, a compound present in several fruits and medicinal plants, has shown anti-inflammatory activity in several experimental disease models. We used the nonlethal acid aspiration model of ALI in mice to determine whether preventive or therapeutic administration of ellagic acid (10 mg/kg; oral route) could interfere with the development or establishment of ALI inflammation. Dexamethasone (1 mg/kg; subcutaneous route) was used as a positive control. In both preventive and therapeutic treatments, ellagic acid reduced the vascular permeability changes and neutrophil recruitment to the bronchoalveolar lavage fluid (BALF) and to lung compared to the vehicle. In addition, the ellagic acid accelerated the resolution for lung neutrophilia. Moreover, ellagic acid reduced the COX-2-induced exacerbation of inflammation. These results were similar to the dexamethasone. However, while the anti-inflammatory effects of dexamethasone treatment were due to the reduced activation of NF- κ B and AP-1, the ellagic acid treatment led to reduced BALF levels of IL-6 and increased levels of IL-10. In addition, dexamethasone treatment reduced IL-1 ß. Together, these findings identify ellagic acid as a potential therapeutic agent for ALI-associated inflammation.
Assuntos
Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Ácido Elágico/uso terapêutico , Ácido Clorídrico/toxicidade , Lesão Pulmonar Aguda/metabolismo , Animais , Feminino , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Camundongos , Camundongos Endogâmicos BALB CRESUMO
PURPOSE: To develop experimental models to evaluate the effects of hydrochloric acid associated with the pepsin instilled in the mucosa of the upper esophagus and the esophagogastric junction of young male rats Wistar, simulating injury caused by gastroesophageal reflux on the mucosa of aero-digestive tract in humans as well as the action of the risk exposure of mucosa to cigarette smoke. METHODS: Fifty young male Wistar rats divided in 5 groups with 10 animals each one, respectively simulating pharyngo-laryngeal reflux and gastroesophageal reflux, pharyngo-laryngeal reflux and smoking, smoking only, gastroesophageal reflux and control group. RESULTS: The histopathologic studies no recorded neoplasias, only mild changes and no significant alterations. The hemo-oximetry (carboxyhemoglobin and methemoglobim) and CO2 concentration confirm that the animals were submitted to high intensity of exposure to carcinogens in tobacco and its derivatives. CONCLUSION: The experimental models were highly efficient, practical, easy to use and economical and can be employed in other similar studies to determine the harmful effects by smoking and reflux.
OBJETIVO: Desenvolver modelos experimentais para avaliar os efeitos do ácido clorídrico associado a pepsina, instilados na mucosa da parte superior do esôfago e da junção esofagogástrica de jovens ratos Wistar, simulando lesão causada por refluxo gastroesofágico na mucosa do trato aero-digestivo em humanos, bem como a ação da exposição ao risco de mucosa, como a fumaça de cigarro. MÉTODOS: Cinqüenta jovens ratos Wistar divididos em cinco grupos com 10 animais cada um, respectivamente, simulando o refluxo faringo-laríngeo e refluxo gastroesofágico, refluxo faringo-laríngeo e tabagismo, tabagismo só, refluxo gastroesofágico e grupo controle. RESULTADOS: os estudos histopatológicos não registraram neoplasias, apenas leves alterações e não significativas. O hemo-oximetria (carboxiemoglobina e metemoglobina) e concentração de CO2 corroboram que os animais foram submetidos a alta intensidade de exposição a substâncias cancerígenas do tabaco e seus derivados. CONCLUSÃO: os modelos experimentais desenvolvidos foram altamente eficientes, práticos, fáceis de usar e econômicos podendo ser empregados em outros estudos semelhantes para determinar os efeitos prejudiciais causados pelo tabagismo e refluxo.
Assuntos
Animais , Masculino , Ratos , Modelos Animais de Doenças , Mucosa Gástrica/efeitos dos fármacos , Refluxo Gastroesofágico/complicações , Fármacos Gastrointestinais/toxicidade , Ácido Clorídrico/toxicidade , Pepsina A/toxicidade , Fumar/efeitos adversos , Testes de Carcinogenicidade , Carcinógenos/toxicidade , Mucosa Gástrica/patologia , Refluxo Gastroesofágico/induzido quimicamente , Refluxo Gastroesofágico/patologia , Distribuição Aleatória , Ratos Wistar , Fumar/fisiopatologiaRESUMO
PURPOSE: To develop experimental models to evaluate the effects of hydrochloric acid associated with the pepsin instilled in the mucosa of the upper esophagus and the esophagogastric junction of young male rats Wistar, simulating injury caused by gastroesophageal reflux on the mucosa of aero-digestive tract in humans as well as the action of the risk exposure of mucosa to cigarette smoke. METHODS: Fifty young male Wistar rats divided in 5 groups with 10 animals each one, respectively simulating pharyngo-laryngeal reflux and gastroesophageal reflux, pharyngo-laryngeal reflux and smoking, smoking only, gastroesophageal reflux and control group. RESULTS: The histopathologic studies no recorded neoplasias, only mild changes and no significant alterations. The hemo-oximetry (carboxyhemoglobin and methemoglobim) and CO2 concentration confirm that the animals were submitted to high intensity of exposure to carcinogens in tobacco and its derivatives. CONCLUSION: The experimental models were highly efficient, practical, easy to use and economical and can be employed in other similar studies to determine the harmful effects by smoking and reflux.
Assuntos
Modelos Animais de Doenças , Mucosa Gástrica/efeitos dos fármacos , Refluxo Gastroesofágico/complicações , Fármacos Gastrointestinais/toxicidade , Ácido Clorídrico/toxicidade , Pepsina A/toxicidade , Fumar/efeitos adversos , Animais , Testes de Carcinogenicidade , Carcinógenos/toxicidade , Mucosa Gástrica/patologia , Refluxo Gastroesofágico/induzido quimicamente , Refluxo Gastroesofágico/patologia , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Fumar/fisiopatologiaRESUMO
The effects of epitaondiol (1) and sargaol (2), isolated from the brown alga Stypopodium flabelliforme on HCl/ethanol-induced gastric lesions in mice were evaluated and compared with that of lansoprazole. Epitaondiol and sargaol (6.25 - 50 mg/kg) dose-dependently inhibited the appearance of gastric lesions in mice, displaying similar values to lansoprazole at 20 mg/kg. Both epitaondiol and sargaol showed gastroprotective activity with ED50 values of 40 mg/kg and 35 mg/kg, respectively. The results suggest that epitaondiol and sargaol protect the gastric mucosa in the HCl/EtOH model in mice.
Assuntos
Antiulcerosos/farmacologia , Etanol/toxicidade , Ácido Clorídrico/toxicidade , Úlcera Gástrica/induzido quimicamente , Terpenos/farmacologia , 2-Piridinilmetilsulfinilbenzimidazóis/farmacologia , Animais , Antiulcerosos/química , Lansoprazol , Camundongos , Estrutura Molecular , Phaeophyceae/química , Fitoterapia , Extratos Vegetais/química , Úlcera Gástrica/prevenção & controle , Terpenos/químicaRESUMO
As part of our continuing search for bioactive natural products from plants, the present study was carried out in order to evaluate the gastroprotective properties of alkaloid extract and 2-phenylquinoline obtained from the bark of Galipea longiflora (Rutaceae). Anti-ulcer assays were performed using the following protocols in mice: nonsteroidal anti-inflammatory drug (NSAID)/bethanecol-induced ulcer, ethanol/HCl-induced ulcer, and stress-induced ulcer. The effects of the extract on gastric content volume, pH and total acidity were also evaluated, using the pylorus ligated model. Treatment using doses of 50, 125 and 250 mg/kg of G. longiflora alkaloid extract and positive controls (omeprazol or cimetidine) significantly diminished the lesion index, total lesion area, and percentage of lesion, in comparison with the negative control groups in all the models evaluated. Regarding the model of gastric secretion, a reduction in volume of gastric juice and total acidity was observed, as well as an increase in gastric pH. The main alkaloid of the plant, 2-phenylquinoline, was also evaluated in the ethanol-induced ulcer model. The results showed that at a dose of 50 mg/kg, it significantly inhibited ulcerative lesions. However, this effect was less than that of the alkaloid extract. All these results taken together show that G. longiflora displays gastroprotective activity, as evidenced by its significant inhibition of the formation of ulcers induced by different models. There are indications that mechanisms involved in anti-ulcer activity are related to a decrease in gastric secretion and an increase in gastric mucus content. Also, there is evidence of involvement of NO in the gastroprotector mechanisms. These effects may be attributed, at least in part, to the presence of some alkaloids, particularly 2-phenylquinoline.
Assuntos
Alcaloides/farmacologia , Extratos Vegetais/farmacologia , Quinolinas/farmacologia , Rutaceae/química , Úlcera Gástrica/prevenção & controle , Alcaloides/química , Animais , Antiulcerosos/química , Antiulcerosos/farmacologia , Betanecol/toxicidade , Relação Dose-Resposta a Droga , Etanol/toxicidade , Ácido Clorídrico/toxicidade , Indometacina/toxicidade , Camundongos , Estrutura Molecular , Casca de Planta/química , Extratos Vegetais/química , Quinolinas/química , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamenteRESUMO
BACKGROUND: Positive end-expiratory pressure (PEEP) and sustained inspiratory insufflations (SI) during acute lung injury (ALI) are suggested to improve oxygenation and respiratory mechanics. We aimed to investigate the hemodynamic effects of PEEP with and without alveolar recruiting maneuver in a mild ALI model induced by inhalation of hydrochloric acid. METHODS: Thirty-two pigs were randomly allocated into four groups (Control-PEEP, Control-SI, ALI-PEEP and ALI-SI). ALI was induced by intratracheal instillation of hydrochloric acid. PEEP values were progressively increased and decreased from 5, 10, 15 and 20 cmH2O in all groups. Three SIs maneuvers of 30 cmH2O for 20 s were applied to the assignable groups between each PEEP level. Transesophageal echocardiography (TEE), global hemodynamics, oxygenation indexes and gastric tonometry were measured 5 min after the maneuvers had been concluded and at each established value of PEEP (5, 10, 15 and 20 cmH2O). RESULTS: The cardiac index, ejection fraction and end-diastolic volume of right ventricle were significantly (P < 0.001) decreased with PEEP in both Control and ALI groups. Left ventricle echocardiography showed a significant decrease in end-diastolic volume at 20 cmH2O of PEEP (P < 0.001). SIs did not exert any significant hemodynamic effects either early (after 5 min) or late (after 3 h). CONCLUSIONS: In a mild ALI model induced by inhalation of hydrochloric acid, significant hemodynamic impairment characterized by cardiac function deterioration occurred during PEEP increment, but SI, probably due to low applied values (30 cmH2O), did not exert further negative hemodynamic effects. PEEP should be used cautiously in ALI caused by acid gastric content inhalation.
Assuntos
Lesão Pulmonar Aguda/terapia , Hemodinâmica , Respiração com Pressão Positiva , Lesão Pulmonar Aguda/sangue , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/patologia , Lesão Pulmonar Aguda/fisiopatologia , Animais , Modelos Animais de Doenças , Ecocardiografia Transesofagiana , Ácido Clorídrico/toxicidade , Insuflação , Pulmão/patologia , Complacência Pulmonar , Masculino , Oxigênio/sangue , Pressão Parcial , Distribuição Aleatória , Aspiração Respiratória , Método Simples-Cego , Volume Sistólico , Sus scrofa , Resistência VascularRESUMO
PURPOSE: To investigate the carcinogenic action of hydrochloric acid, pepsin and sodium nitrate on the oropharyngeal mucosa of rats, simulating the reflux of gastric contents. METHODS: Eighty-two Wistar rats were divided in seven groups and submitted to 2 or 3 weekly applications of hydrochloric acid, pepsin and sodium nitrate on the pharyngeal mucosa during six months. Study groups comprised 12 animals each. Rats in groups I and II were submitted to 2 (GI) or 3 (GII) weekly applications of 0.1N hydrochloric acid. Groups III and IV were submitted to 2 (GIII) or 3 (GIV) weekly applications of 0.1N hydrochloric acid solution with pepsin. Groups V and VI were submitted to 2 (GV) or 3 (GVI) weekly applications of 0.1N hydrochloric acid and treated with daily nitrate diluted in water. Group VII consisted of 10 animals submitted to 2 weekly applications of filtered water. RESULTS: No dysplasia, intra-epithelial neoplasia or invasive carcinomas were detected. Inflammatory changes were observed in varying degrees and mast cells were more common in Groups V and VI (p=0.006). CONCLUSION: The data of the current study could not corroborate the hypothesis that gastroesophageal and pharyngolaryngeal refluxes are carcinogenic factors to the laryngopharyngeal mucosa, and more studies are necessary in the future.
OBJETIVO: Investigar a ação carcinogênica do ácido clorídrico, pepsina e nitrato de sódio na mucosa orofaríngea de ratos, simulando o refluxo do conteúdo gástrico à mucosa do faringo-laringea. MÉTODOS: Oitenta e dois ratos Wistar foram divididos em 7 grupos e submetidos a 2 ou 3 aplicações semanais de ácido clorídrico, pepsina e nitrato de sódio na mucosa orofaríngea durante 6 meses. Os grupos de estudo envolveram 12 animais cada. Os ratos nos grupos I e II foram submetidos à 2 (GI) ou 3 (GII) aplicações semanais de ácido clorídrico 0,1N. Nos grupos III e IV foram 2 (GIII) ou 3 (GIV) aplicações semanais de ácido clorídrico e pepsina. Nos grupos V e VI foram 2 (GV) ou 3 (GVI) aplicações semanais de ácido clorídrico além da oferta de nitrato diluído em água diariamente. Grupo VII era composto por 10 animais submetidos a 2 aplicações semanais de água filtrada. RESULTADOS: Não se observou displasia, neoplasia intra-epitelial ou neoplasia invasora. Alterações inflamatórias em graus variados foram observadas, com infiltrado mastocitário mais intenso nos grupos V e VI. (p=0,006). CONCLUSÃO: Os dados do presente estudo não confirmam a hipótese que o refluxo gastro-esofágico e faringo-laringeo são fatores carcinogênicos para a mucosa laringo-faringea e mais estudos são necessários no futuro.