RESUMO
The aim of this study was to investigate the role of alpha2-adrenoceptors in the mechanism of intragastric polyethylene glycol 400 (PEG-400) protection against ethanol-induced gastric mucosal damage. In the injury study, 0.5 hr after subcutaneous control or yohimbine (5 mg/kg), a selective alpha2-adrenoceptor antagonist, rats were treated with intragastric vehicle or PEG-400 (5500 mg/kg). One hour later animals received 96% ethanol (gavage needle), 5 ml/kg, and the rats were killed after another hour. Total lengths of the gastric mucosal lesions were measured by an unbiased observer in a blinded fashion using a binocular magnifier having 5x magnification. In a separate set of experiments, 0.5 hr after subcutaneous control or yohimbine (5 mg/kg) rats received intragastric vehicle or PEG-400 (5500 mg/kg). One hour later gastric mucus volume, gastric juice volume, and gastric acid output in the gastric juice were measured. The protective effect offered by intragastric PEG-400 against ethanol-induced gastric mucosal damage was significantly diminished although not completely abolished by a selective alpha2-adrenoceptor antagonist (yohimbine). Yohimbine also significantly diminished both the basal and PEG-400-stimulated increase in gastric mucus volume. These findings suggest that the protective effect afforded by intragastric PEG-400 against ethanol-induced gastric mucosal damage is partially mediated by alpha2-adrenoceptors, and a mucus-dependent mechanism may be involved.
Assuntos
Antagonistas de Receptores Adrenérgicos alfa 2 , Antagonistas Adrenérgicos alfa/farmacologia , Etanol/toxicidade , Mucosa Gástrica/efeitos dos fármacos , Polietilenoglicóis/farmacologia , Tensoativos/farmacologia , Ioimbina/farmacologia , Animais , Feminino , Ácido Gástrico/metabolismo , Suco Gástrico/metabolismo , Mucosa Gástrica/metabolismo , Masculino , Muco/metabolismo , Polietilenoglicóis/administração & dosagem , Ratos , Ratos Wistar , Receptores Adrenérgicos alfa 2/fisiologia , Tensoativos/administração & dosagemRESUMO
Intragastric administration of clarithromycin, a macrolide antibiotic, macroscopically protected the rat gastric mucosa from 96% ethanol-induced lesions. This protective effect was dose-dependent, the reduction being 92.3, 81.4, 52.2, and 5.4% at doses of 400, 200, 100, and 50 mg/kg, respectively. Clarithromycin protection was not significantly modified by pretreatment with either subcutaneous indomethacin (5 mg/kg), a selective cyclooxygenase inhibitor, or iodoacetamide (100 mg/kg), a specific sulfhydryl blocker. Gastric motor activity, measured by the balloon method, was inhibited by clarithromycin in a dose-dependent fashion. The inhibited gastric motor activity induced by clarithromycin was not modified by pretreatment with either indomethacin or iodoacetamide. Ethanol (1 ml/rat, gavage needle) induced hemorrhagic bandlike lesions in the mucosa of the glandular stomach along the long axis of the greater curvature with the occurrence of a complete inhibition of gastric motor activity. This inhibition was not modified by pretreatment with clarithromycin, indomethacin, or iodoacetamide. There was an increase in the fluid volume for clarithromycin at 100, 200, and 400 mg/kg at 30 min and in the mucus volume only for clarithromycin at 400 mg/kg at 30 min. Gastric mucosal blood flow was absent in the ethanol-induced lesions but in the nonlesion areas was the same in clarithromycin-pretreated and vehicle-pretreated rats as in control (no ethanol) rats. Clarithromycin protection was significantly diminished, although not completely abolished by subcutaneous yohimbine (5 mg/kg), a selective alpha2-adrenoceptor antagonist. Yohimbine also significantly reduced both basal and clarithromycin-stimulated gastric mucus secretion. Our data support the conclusion that the protective effect of intragastric clarithromycin was not mediated by endogenous prostaglandins, sulfhydryl compounds of the gastric mucosa, or changes in the gastric contractile patterns. The protection may be the result of an increase in both the fluid volume and the mucus volume retained in the gastric lumen. alpha2-Adrenoceptors possibly are involved by the mucus-dependent mechanism.
Assuntos
Antibacterianos/administração & dosagem , Claritromicina/administração & dosagem , Etanol , Gastropatias/induzido quimicamente , Estômago/efeitos dos fármacos , Antagonistas Adrenérgicos alfa/farmacologia , Animais , Antibacterianos/farmacologia , Água Corporal/efeitos dos fármacos , Claritromicina/farmacologia , Inibidores de Ciclo-Oxigenase/farmacologia , Feminino , Mucosa Gástrica/irrigação sanguínea , Mucosa Gástrica/patologia , Conteúdo Gastrointestinal/efeitos dos fármacos , Motilidade Gastrointestinal/efeitos dos fármacos , Indometacina/farmacologia , Iodoacetamida/farmacologia , Masculino , Ratos , Ratos Wistar , Fluxo Sanguíneo Regional/efeitos dos fármacos , Gastropatias/patologia , Reagentes de Sulfidrila/farmacologia , Ioimbina/farmacologiaRESUMO
The influence of water-immersion stress on gastric acid secretion, and the effect of acetazolamide (a potent carbonic anhydrase inhibitor) on acid secretion, and gastric mucosal lesion formation in rats under water-immersion stress were studied. Acid secretion in pylorus-ligated rats decreased under a 10_h stress period as compared with that of rats under normal conditions. Intraperitoneal administration of acetazolamide (100, 50, 25 mg/kg every 5 h for a total of two times) which significantly inhibited acid secretion in a dose-dependent fashion of stressed rats, prevented the development of gastric mucosal lesions produced by stress. Non antisecretory dose of acetazolamide (5 mg/kg, intraperitoneal administration every 5 h for a total of two times) did not prevent the formation of gastric mucosal lesions. Stress ulcer aggravation by acid administration (150 mM HCl, 0.5 ml/h) into the stomach during the stress was not prevented by treatment with antisecretory acetazolamide dose. We conclude that: (1) the exposure of rats to water-immersion stress for 10 h decreases gastric acid secretion, and (2) acetazolamide suppresses water-immersion stress-induced gastric lesions by inhibiting acid secretion.
Assuntos
Acetazolamida/farmacologia , Inibidores da Anidrase Carbônica/farmacologia , Ácido Gástrico/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Imersão , Úlcera Gástrica , Estresse Fisiológico , Água , Animais , Feminino , Masculino , Ratos , Ratos WistarRESUMO
En ratas con píloro ligado, la secreción ácida gástrica (volumen y débito) de los animales en estrés por 10 h (inmovilización e inmersión en agua (21 grados celsius) fue significativamente menor que la de las ratas sin estrés. Acetazolomida, un potente inhibidor de la anhidrasa carbónica, administrada por vía intraperitoneal cada 5 h por un total de dos veces, dosis dependientemente (100, 50, 25 mg/kg) inhibió la secreción ácida y la formación de lesiones mucosas gástricas inducidas por el estrés (dosis antisecretoras). La acetazolamida (5 mg/kg) no tuvo efecto sobre dos parámetros (dosis noantisecretora). El incremento de las lesiones mucosas gástricas inducidas por la instilación intragástrica de 150 mM HCL (0.5 ml/h) durante el estrés, no fueinhibido por dosis antisecretoras de acetazolamida. Se concluye que: (1) la exposición de ratas por 10 h de estrés (inmovilización e inmersión en agua) disminuye la secreción ácida gástrica (2) la acetazolamida, inhibiendo la secreción ácida gástrica protégé a la mucosa de las lesiones inducidas por el estrés y (3) una mínima cantidad de ácido en el lumen gástrico es suficiente para desarrollar las lesiones inducidas por este tipo de estrés.
Assuntos
Animais , Feminino , Ratos , Acetazolamida/farmacologia , Inibidores da Anidrase Carbônica/farmacologia , Ácido Gástrico/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Imersão , Úlcera Gástrica , Estresse Fisiológico , Água , Ratos WistarRESUMO
The influence of water-immersion stress on gastric acid secretion, and the effect of acetazolamide (a potent carbonic anhydrase inhibitor) on acid secretion, and gastric mucosal lesion formation in rats under water-immersion stress were studied. Acid secretion in pylorus-ligated rats decreased under a 10_h stress period as compared with that of rats under normal conditions. Intraperitoneal administration of acetazolamide (100, 50, 25 mg/kg every 5 h for a total of two times) which significantly inhibited acid secretion in a dose-dependent fashion of stressed rats, prevented the development of gastric mucosal lesions produced by stress. Non antisecretory dose of acetazolamide (5 mg/kg, intraperitoneal administration every 5 h for a total of two times) did not prevent the formation of gastric mucosal lesions. Stress ulcer aggravation by acid administration (150 mM HCl, 0.5 ml/h) into the stomach during the stress was not prevented by treatment with antisecretory acetazolamide dose. We conclude that: (1) the exposure of rats to water-immersion stress for 10 h decreases gastric acid secretion, and (2) acetazolamide suppresses water-immersion stress-induced gastric lesions by inhibiting acid secretion.
RESUMO
En ratas con píloro ligado, la secreción ácida gástrica (volumen y débito) de los animales en estrés por 10 h (inmovilización e inmersión en agua (21 grados celsius) fue significativamente menor que la de las ratas sin estrés. Acetazolomida, un potente inhibidor de la anhidrasa carbónica, administrada por vía intraperitoneal cada 5 h por un total de dos veces, dosis dependientemente (100, 50, 25 mg/kg) inhibió la secreción ácida y la formación de lesiones mucosas gástricas inducidas por el estrés (dosis antisecretoras). La acetazolamida (5 mg/kg) no tuvo efecto sobre dos parámetros (dosis noantisecretora). El incremento de las lesiones mucosas gástricas inducidas por la instilación intragástrica de 150 mM HCL (0.5 ml/h) durante el estrés, no fueinhibido por dosis antisecretoras de acetazolamida. Se concluye que: (1) la exposición de ratas por 10 h de estrés (inmovilización e inmersión en agua) disminuye la secreción ácida gástrica (2) la acetazolamida, inhibiendo la secreción ácida gástrica protégé a la mucosa de las lesiones inducidas por el estrés y (3) una mínima cantidad de ácido en el lumen gástrico es suficiente para desarrollar las lesiones inducidas por este tipo de estrés. (AU)
Assuntos
Animais , Feminino , Ratos , Ácido Gástrico/metabolismo , Água , Imersão , Estresse Fisiológico , Úlcera Gástrica , Acetazolamida/farmacologia , Inibidores da Anidrase Carbônica/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Ratos WistarRESUMO
The purpose of this study was to investigate the role played by endogenous prostaglandins, sulfhydryls, gastric motility, fluid volume, and mucus volume retained in the gastric lumen in the protection offered by intragastric amoxicillin against ethanol-induced gastric lesions. It has been demonstrated that intragastric administration of amoxicillin (Amx) dose-dependently protected the rat gastric mucosa from 96% ethanol-induced lesions. The inhibition of the lesions was 28, 41.4, 84.7 and 90% at doses of 50, 100, 200 and 400 mg/kg, respectively. The gastroprotective effect of Amx was significantly reversed by pretreatment with both indomethacin (5 mg/kg, subcutaneously), a cyclooxygenase inhibitors, and iodoacetamide (100 mg/kgm subcutaneously), a sulfhydryl blocker. Gastric motility was measured by a balloon method. There was not any significant differences between Amx (50-400 mg/kg)-induced and spontaneous motility with regard to both amplitudes and frequently of gastric contraction. One milliliter of 96% ethanol produced hemorrhagic bandlike lesions in the corpus mucosa with the occurrence of a complete inhibition of the amplitude and frequency of gastric contraction. This inhibition of gastric motility caused by ethanol was not modified by pretreatment of Amx (400 mg/kg) alone, indomethacin plus Amx or iodoacetamide plus Amx. In addition, there was a significant increase in the mucus volume retained in the gastric lumen for Amx (200 and 400 mg/kg) at 30 min after its administration. We conclude that the intragastric Amx prospective effect against 96% eathanol-induced mucosal lesions may be mediated by endogenous prostaglandins, sulfhydryl compounds of the gastric mucosa, an increase in mucus volume retained in the gastric lumen at the time when ethanol is administered, and is not associated with the gastric motor activity.
Assuntos
Amoxicilina/farmacologia , Etanol/toxicidade , Mucosa Gástrica/efeitos dos fármacos , Penicilinas/farmacologia , Prostaglandinas/metabolismo , Análise de Variância , Animais , Interações Medicamentosas , Feminino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Motilidade Gastrointestinal/efeitos dos fármacos , Indometacina/farmacologia , Iodoacetamida/farmacologia , Masculino , Coelhos , Ratos , Ratos WistarRESUMO
The purpose of this study was to investigate the role played by endogenous prostaglandins, sulfhydryls, gastric motility, fluid volume, and mucus volume retained in the gastric lumen in the protection offered by intragastric amoxicillin against ethanol-induced gastric lesions. It has been demonstrated that intragastric administration of amoxicillin (Amx) dose-dependently protected the rat gastric mucosa from 96 per cent ethanol-induced lesions. The inhibition of the lesions was 28, 41.4, 84.7 and 90 per cent at doses of 50, 100, 200 and 400 mg/Kg, respectively. The gastroprotective effect of Amx was significantly reversed by pretreatment with both indomethacin (5 mg/Kg, subcutaneously), a cyclooxygenase inhibitors, and iodoacetamide (100 mg/Kgm subcutaneously), a sulfhydryl blocker. Gastric motility was measured by a ballon method. There was not any significant differences between Amx (50-400 mg/Kg)-induced and spontaneous motility with regard to both amplitudes and frequently of gastric contraction. One milliliter of 96 per cent ethanol produced hemorrhagic bandlike lesions in the corpus mucosa with the occurrence of a complete inhibition of the amplitude and frequency of gastric contraction. This inhibition of gastric motility caused by ethanol was not modified by pretreatment of Amx (400 mg/Kg) alone, indomethacin plus Amx or iodoacetamide plus Amx. In addition, there was a significant increase in the mucus volume retained in the gastric lumen for Amx (200 and 400 mg/Kg) at 30 min after its adminitration. We conclude that the intragastric Amx prospective effect aginst 96 per cent athanol-induced mucosal lesions may be mediated by endogenous prostaglandins, sulfhydryl compounds of the gastric mucosa, an increase in mucus volume retained in the gastric lumen at the time when ethanol is administered, and is not associated with the gastric motor activity.
Assuntos
Animais , Feminino , Ratos , Amoxicilina/farmacologia , Etanol/toxicidade , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Penicilinas/farmacologia , Prostaglandinas/metabolismo , Análise de Variância , Interações Medicamentosas , Mucosa Gástrica/metabolismo , Motilidade Gastrointestinal/efeitos dos fármacos , Indometacina/farmacologia , Iodoacetamida/farmacologia , Ratos WistarRESUMO
The purpose of this study was to investigate the role played by endogenous prostaglandins, sulfhydryls, gastric motility, fluid volume, and mucus volume retained in the gastric lumen in the protection offered by intragastric amoxicillin against ethanol-induced gastric lesions. It has been demonstrated that intragastric administration of amoxicillin (Amx) dose-dependently protected the rat gastric mucosa from 96 per cent ethanol-induced lesions. The inhibition of the lesions was 28, 41.4, 84.7 and 90 per cent at doses of 50, 100, 200 and 400 mg/Kg, respectively. The gastroprotective effect of Amx was significantly reversed by pretreatment with both indomethacin (5 mg/Kg, subcutaneously), a cyclooxygenase inhibitors, and iodoacetamide (100 mg/Kgm subcutaneously), a sulfhydryl blocker. Gastric motility was measured by a ballon method. There was not any significant differences between Amx (50-400 mg/Kg)-induced and spontaneous motility with regard to both amplitudes and frequently of gastric contraction. One milliliter of 96 per cent ethanol produced hemorrhagic bandlike lesions in the corpus mucosa with the occurrence of a complete inhibition of the amplitude and frequency of gastric contraction. This inhibition of gastric motility caused by ethanol was not modified by pretreatment of Amx (400 mg/Kg) alone, indomethacin plus Amx or iodoacetamide plus Amx. In addition, there was a significant increase in the mucus volume retained in the gastric lumen for Amx (200 and 400 mg/Kg) at 30 min after its adminitration. We conclude that the intragastric Amx prospective effect aginst 96 per cent athanol-induced mucosal lesions may be mediated by endogenous prostaglandins, sulfhydryl compounds of the gastric mucosa, an increase in mucus volume retained in the gastric lumen at the time when ethanol is administered, and is not associated with the gastric motor activity. (AU)
Assuntos
Animais , Feminino , Ratos , Etanol/toxicidade , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Prostaglandinas/metabolismo , Amoxicilina/farmacologia , Penicilinas/farmacologia , Mucosa Gástrica/metabolismo , Ratos Wistar , Motilidade Gastrointestinal/efeitos dos fármacos , Interações Medicamentosas , Análise de Variância , Iodoacetamida/farmacologia , Indometacina/farmacologiaRESUMO
Thioctic acid, a sulfhydryl agent, given orally macroscopically protected the gastric mucosa from 96 percent ethanol-induced lesions in a dose-and time dependent fashion. The inhibition of the lesions was 56.0 and 90.3 percent at doses of 25 and 50 mg/Kg, respectively. The duration of its protective effect was appoximately 120 minutes. Histopathologically, the oral administration of thioctic acid prevented necrotic mucosal lesions in the deeper part of the mucosa but did not protect the surface epithelial cells against ethanol challenge. Gastric motility measured by a ballon method, was dose-dependently inhibited by the oral administration of thioctic acid. Thioctic acid protection was suppressed by pretreatment with indomethacin (30 mg/Kg), a cyclooxygenase inhibitor, and iodoacetamide (100 mg/Kg), a sulfhydryl bloker. The gastric motility inhibited by oral thioctic acid was not reversed by indomethacin or iodoacetamide. These doses of indomethacin or iodomethamide were administered because previously they had been used to suppress endogenous prostagladins, and nonprotein sulfhydryls of the gastric mucosa, respectively. There was an increase in the fluid volume retained in the gastric lumen for thioctic acid (50 mg/Kg) at 30,60,90, and 120 minutes after administration. There was an increase in the mucus volume retained in the gastric lumen for thioctic acid (50, 25 mg/Kg) at 120 minutes after administration. The lesion area in the rats treated with 70 mul of vehicle and in the rats treated with 250 mul of vehicle were significantly higher than in the rats treated with 450 mul of vehicle. The present study suggests that thioctic acid administered orally, affered protection to the rat gastric mucosa against 96 percent ethanol-induced lesions. This protective effect appears to be dependent on prostagladin-and sulfhydryl-sensitive mechanisms, together with an increase in both the fluid volume and the mucus volume retained in the gastric lumen, and is not associated with the inhibition of gastric motor activity.
Assuntos
Ratos , Feminino , Animais , Etanol/toxicidade , Mucosa Gástrica/lesões , Muco/efeitos dos fármacos , Prostaglandinas/fisiologia , Compostos de Sulfidrila/fisiologia , Ácido Tióctico/farmacologia , Análise de Variância , Etanol/toxicidade , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Motilidade Gastrointestinal/efeitos dos fármacos , Indometacina/farmacologia , Iodoacetamida/farmacologia , Muco/metabolismo , Ratos Wistar , Fatores de TempoRESUMO
Thioctic acid, a sulfhydryl agent, given orally macroscopically protected the gastric mucosa from 96 percent ethanol-induced lesions in a dose-and time dependent fashion. The inhibition of the lesions was 56.0 and 90.3 percent at doses of 25 and 50 mg/Kg, respectively. The duration of its protective effect was appoximately 120 minutes. Histopathologically, the oral administration of thioctic acid prevented necrotic mucosal lesions in the deeper part of the mucosa but did not protect the surface epithelial cells against ethanol challenge. Gastric motility measured by a ballon method, was dose-dependently inhibited by the oral administration of thioctic acid. Thioctic acid protection was suppressed by pretreatment with indomethacin (30 mg/Kg), a cyclooxygenase inhibitor, and iodoacetamide (100 mg/Kg), a sulfhydryl bloker. The gastric motility inhibited by oral thioctic acid was not reversed by indomethacin or iodoacetamide. These doses of indomethacin or iodomethamide were administered because previously they had been used to suppress endogenous prostagladins, and nonprotein sulfhydryls of the gastric mucosa, respectively. There was an increase in the fluid volume retained in the gastric lumen for thioctic acid (50 mg/Kg) at 30,60,90, and 120 minutes after administration. There was an increase in the mucus volume retained in the gastric lumen for thioctic acid (50, 25 mg/Kg) at 120 minutes after administration. The lesion area in the rats treated with 70 mul of vehicle and in the rats treated with 250 mul of vehicle were significantly higher than in the rats treated with 450 mul of vehicle. The present study suggests that thioctic acid administered orally, affered protection to the rat gastric mucosa against 96 percent ethanol-induced lesions. This protective effect appears to be dependent on prostagladin-and sulfhydryl-sensitive mechanisms, together with an increase in both the fluid volume and the mucus volume retained in the gastric lumen, and is not associated with the inhibition of gastric motor activity. (AU)
Assuntos
Ratos , Feminino , Animais , Ácido Tióctico/farmacologia , Mucosa Gástrica/lesões , Muco/efeitos dos fármacos , Compostos de Sulfidrila/fisiologia , Prostaglandinas/fisiologia , Etanol/toxicidade , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Muco/metabolismo , Motilidade Gastrointestinal/efeitos dos fármacos , Ratos Wistar , Análise de Variância , Fatores de Tempo , Indometacina/farmacologia , Iodoacetamida/farmacologia , Etanol/toxicidadeRESUMO
Thioctic acid, a sulfhydryl agent, given orally macroscopically protected the gastric mucosa from 96% ethanol-induced lesions in a dose-and time dependent fashion. The inhibition of the lesions was 56.0 and 90.3% at doses of 25 and 50 mg/kg, respectively. The duration of its protective effect was approximately 120 minutes. Histopathologically, the oral administration of thioctic acid prevented necrotic mucosal lesions in the deeper part of the mucosa but did not protect the surface epithelial cells against ethanol challenge. Gastric motility measured by a balloon method, was dose-dependently inhibited by the oral administration of thioctic acid. Thioctic acid protection was suppressed by pretreatment with indomethacin (30 mg/kg), a cyclooxygenase inhibitor, and iodoacetamide (100 mg/kg), a sulfhydryl blocker. The gastric motility inhibited by oral thioctic acid was not reversed by indomethacin or iodoacetamide. These doses of indomethacin or iodomethamide were administered because previously they had been used to suppress endogenous prostaglandins, and nonprotein sulfhydryls of the gastric mucosa, respectively. There was an increase in the fluid volume retained in the gastric lumen for thioctic acid (50 mg/kg) at 30, 60, 90, and 120 minutes after administration. There was an increase in the mucus volume retained in the gastric lumen for thioctic acid (50, 25 mg/kg) at 120 minutes after administration. The lesion area in the rats treated with 70 microliters of vehicle and in the rats treated with 250 microliters of vehicle were significantly higher than in the rats treated with 450 microliters of vehicle. The present study suggests that thioctic acid administered orally, offered protection to the rat gastric mucosa against 96% ethanol-induced lesions. This protective effect appears to be dependent on prostaglandin-and sulfhydryl-sensitive mechanisms, together with an increase in both the fluid volume and the mucus volume retained in the gastric lumen, and is not associated with the inhibition of gastric motor activity.
Assuntos
Etanol/toxicidade , Mucosa Gástrica/efeitos dos fármacos , Muco/efeitos dos fármacos , Prostaglandinas/fisiologia , Compostos de Sulfidrila/fisiologia , Ácido Tióctico/uso terapêutico , Análise de Variância , Animais , Feminino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Motilidade Gastrointestinal/efeitos dos fármacos , Indometacina/farmacologia , Iodoacetamida/farmacologia , Masculino , Muco/metabolismo , Ratos , Ratos Wistar , Fatores de TempoRESUMO
BACKGROUND/AIMS: The gastric protective effect of thioctic acid, a sulfhydryl compound, against chemically induced mucosal lesions has not been reported. METHODS: Fasted Wistar rats (24 h) were treated (gavage administration) with graded doses of thiotic acid (12.5, 25, 37.5, 50 mg/kg) followed 0.5 h later by the gavage administration of 1 ml 96% ethanol or intraperitoneal administered indomethacin. The gastric mucosa was examined grossly and histologically for an evaluation of the lesions. RESULTS: Pretreatment of rats with thiotic acid has shown a significant decline in the mean number, size, incidence and severity of mucosal lesions induced by both ethanol and indomethacin. CONCLUSIONS: This is the first evidence that thiotic acid protects the rat gastric mucosa against chemically induced damage. Its is speculated that this finding may prove to be important in the development of improved therapies for the prevention and treatment of gastric ulcers in humans.
Assuntos
Etanol/efeitos adversos , Mucosa Gástrica/efeitos dos fármacos , Indometacina/efeitos adversos , Gastropatias/prevenção & controle , Ácido Tióctico/uso terapêutico , Animais , Feminino , Mucosa Gástrica/patologia , Masculino , Ratos , Ratos Wistar , Gastropatias/induzido quimicamenteRESUMO
Background/Aims: The gastric protective effect of thioctic acid, a sulfhydryl compund, against chemically induced mucosal lesions has not been reported. Methods: Fasted Wistar rats (24 h) were treated (gavage administration) with graded doses of thiotic acid (12.5, 25, 37.5, 50 mg/kg) followed 0.5 h later by the gavage administration of 1 ml 96 per cent ethanol or intraperitoneal administered indomethacin. The gastric mucosa was examined grossly and histologically for an evaluation of the lesions. Results: Pretreatment of rats with thotic acid has shown a significant decline in the mean number, size, incidence and severity of mucosal lesions induced by both ethanol and indomethacin. Conclusions: This is the first evidence that thiotic acid protects the rat gastric mucosa against chemically induced damage. Its is speculated that this finding may prove to be important in the development of improved therapies for the prevention and treatment of gastric ulcers in humans.
Assuntos
Ratos , Animais , Feminino , Mucosa Gástrica/efeitos dos fármacos , Ácido Tióctico/farmacologia , Etanol , Mucosa Gástrica/patologia , Indometacina , Ratos Wistar , Gastropatias/induzido quimicamenteRESUMO
Background/Aims: The gastric protective effect of thioctic acid, a sulfhydryl compund, against chemically induced mucosal lesions has not been reported. Methods: Fasted Wistar rats (24 h) were treated (gavage administration) with graded doses of thiotic acid (12.5, 25, 37.5, 50 mg/kg) followed 0.5 h later by the gavage administration of 1 ml 96 per cent ethanol or intraperitoneal administered indomethacin. The gastric mucosa was examined grossly and histologically for an evaluation of the lesions. Results: Pretreatment of rats with thotic acid has shown a significant decline in the mean number, size, incidence and severity of mucosal lesions induced by both ethanol and indomethacin. Conclusions: This is the first evidence that thiotic acid protects the rat gastric mucosa against chemically induced damage. Its is speculated that this finding may prove to be important in the development of improved therapies for the prevention and treatment of gastric ulcers in humans. (AU)
Assuntos
Ratos , Animais , Feminino , Mucosa Gástrica/efeitos dos fármacos , Ácido Tióctico/farmacologia , Ratos Wistar , Mucosa Gástrica/patologia , Gastropatias/induzido quimicamente , Indometacina , EtanolRESUMO
It has been shown that intragastric administration of polyethylene glycol-400 (PEG-400) by gavage needle protected the rat gastric mucosa from 96% ethanol-induced lesions in a dose-dependent fashion. The inhibitions of the lesions were 10.5, 53.5, 94.6, and 99.2% at doses of 275, 1375, 2750, and 5500 mg/kg, respectively. The duration of the protective effect was approximately 12 hr. The gastroprotection offered by PEG-400 was not modified by pretreatment with either subcutaneous indomethacin (25 mg/kg) or iodoacetamide (100 mg/kg). Gastric motility, measured by a balloon method, was dose-dependently inhibited by intragastric administration of PEG-400. The inhibited gastric motility (amplitude gastric contraction) induced by PEG-400 was not modified by pretreatment with either indomethacin or iodoacetamide. The gastric emptying rate, investigated by measuring the disappearance of intragastrically administered [99mTc]DTPA from the stomach of rats treated with PEG-400 (5500 mg/kg) was markedly retarded. There was an increase in both the fluid volume and the mucus volume retained in the gastric lumen only for PEG-400 (5500 mg/kg) at 1, 2, and 4 hr after administration. The rats treated with 0.7 ml of vehicle plus 96% ethanol had significantly less damage than those treated with 0.2 ml of vehicle plus 96% ethanol. These results indicate that intragastric PEG-400-protective effect was not mediated by endogenous prostaglandins, sulfhydryl compounds of the gastric mucosa, or changes in gastric contractile patterns. We conclude that the protective effect of intragastric PEG-400 may be the result of retarded gastric emptying together with an osmotic pull of fluid into the stomach and the increase in gastric mucus volume.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Inibidores de Ciclo-Oxigenase/farmacologia , Etanol/efeitos adversos , Mucosa Gástrica/efeitos dos fármacos , Indometacina/farmacologia , Iodoacetamida/farmacologia , Polietilenoglicóis/farmacologia , Reagentes de Sulfidrila/farmacologia , Animais , Relação Dose-Resposta a Droga , Feminino , Esvaziamento Gástrico/efeitos dos fármacos , Motilidade Gastrointestinal/efeitos dos fármacos , Masculino , Polietilenoglicóis/administração & dosagem , Pré-Medicação , Cintilografia , Ratos , Ratos Wistar , Estômago/diagnóstico por imagem , Pentetato de Tecnécio Tc 99m , Fatores de TempoRESUMO
Effects of necrotizing agents, blockers of gastric motility, and mild irritants on gastric mucosa and gastric motility were investigated in conscious rats. Gastric motor activity was recorded using a miniature balloon placed in the glandular part of the stomach, which was connected to a pressure transducer and polygraph. Necrotizing agents, such as 96% ethanol, 0.6 N hydrochloric acid, 0.2 N sodium hydroxide, or 4 M sodium chloride, were given intragastrically through a fistula on the forestomach. One milliliter of these agents produced hemorrhagic bandlike lesions in the corpus mucosa along the long axis of the stomach with the occurrence of a complete inhibition of gastric motility (smooth muscle relaxation). Blockers of gastric motility alone, such as subcutaneous papaverine HCl (50 mg/kg), and intraperitoneal verapamil (20 mg/kg), or mild irritants (1 ml/rat, orally) such as 20% ethanol or 1 M NaCl, which by themselves suppressed gastric motility, have no effect on gastric mucosa and on the inhibited gastric motility induced by necrotizing agents. Bandlike lesions were significantly prevented by pretreatment with 20% ethanol or 1 M NaCl but not with papaverine HCl or verapamil administered 30 min before necrotizing agents. The gastroprotection offered by 20% ethanol or 1 M NaCl was significantly diminished by pretreatment with subcutaneous indomethacin (30 mg/kg), but the inhibited gastric motility was not reversed by indomethacin. These results indicate that it seems unlikely that gastric contractile activity would play a major role in the development and prevention of gastric lesions after the administration of necrotizing agents.
Assuntos
Etanol/efeitos adversos , Motilidade Gastrointestinal/efeitos dos fármacos , Ácido Clorídrico/efeitos adversos , Papaverina/farmacologia , Compostos de Sódio/efeitos adversos , Úlcera Gástrica/prevenção & controle , Verapamil/farmacologia , Animais , Feminino , Indometacina/farmacologia , Masculino , Ratos , Ratos Wistar , Cloreto de Sódio/efeitos adversos , Hidróxido de Sódio/efeitos adversos , Úlcera Gástrica/induzido quimicamenteRESUMO
The aim of this study was to test the hypothesis that protective effect of subcutaneous acetazolamide, a carbonic anhydrase inhibitor, against ethanol-induced gastric mucosal damage is dependent on indomethacin- or iodoacetamide-sensitive mechanisms. In addition we studied the effects of acetazolamide on gastric motility and the influence of indomethacin and iodoacetamide on this parameter. Indomethacin (30 mg/kg) or iodoacetamide (100 ag/kg) was administered subcutaneously in doses that previously had been demonstrated to inhibit endogenous prostaglandins synthesis and gastric mucosal sulfhydryls respectively. At 30 min after these or control subcutaneous pretreatment, the rats were given subcutaneous acetazolamide or vehicle. Thirty min later 96% ethanol was administered orally and the rats were sacrificed 60 min after ethanol administration. The lesions of the gastric glandular mucosa were measured in length and width and expressed in square millimeters. Gastric motility was recorded by a balloon method. The results showed that neither indomethacin nor iodoacetamide aggravated ethanol-induced gastric mucosal damage. The protective effect of subcutaneous acetazolamide was suppressed by pretreatment with indomethacin but not with that of iodoacetamide. Acetazolamide inhibited gastric motility in a dose-dependent fashion. The inhibited gastric motility induced by acetazolamide was reversed by indomethacin but not by iodoacetamide. A highly significant relationship was found between the inhibitory effect of acetazolamide on the motor activity and the mucosal lesions (r +/- 0.8777, P < 0.01). We conclude that the mechanism mediating subcutaneous acetazolamide protection against 96% ethanolinduced gastric mucosal lesions is dependent on indomethacin- and independent of iodoacetamide sensitive mechanisms.
Assuntos
Acetazolamida/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Motilidade Gastrointestinal/efeitos dos fármacos , Prostaglandinas/fisiologia , Compostos de Sulfidrila/fisiologia , Acetazolamida/administração & dosagem , Animais , Relação Dose-Resposta a Droga , Etanol/efeitos adversos , Etanol/antagonistas & inibidores , Feminino , Ácido Gástrico/metabolismo , Indometacina/farmacologia , Injeções Subcutâneas , Iodoacetamida/farmacologia , Masculino , Ratos , Ratos Wistar , Fatores de TempoRESUMO
The aim of this study was to test the hypothesis that protective effect of subcutaneous acetazolamide, a carbonic anhydrase inhibitor, against ethanol-induced gastric mucosal damage is dependent on indomethacin- or iodoacetamide-sensitive mechanisms. In addition we studied the effects of acetazolamide on gastric motility and the influence of indomethacin and iodoacetamide on this parameter. Indomethacin (30 mg/kg) or iodoacetamide (100 ag/kg) was administered subcutaneously in doses that previously had been demonstrated to inhibit endogenous prostaglandins synthesis and gastric mucosal sulfhydryls respectively. At 30 min after these or control subcutaneous pretreatment, the rats were given subcutaneous acetazolamide or vehicle. Thirty min later 96
ethanol was administered orally and the rats were sacrificed 60 min after ethanol administration. The lesions of the gastric glandular mucosa were measured in length and width and expressed in square millimeters. Gastric motility was recorded by a balloon method. The results showed that neither indomethacin nor iodoacetamide aggravated ethanol-induced gastric mucosal damage. The protective effect of subcutaneous acetazolamide was suppressed by pretreatment with indomethacin but not with that of iodoacetamide. Acetazolamide inhibited gastric motility in a dose-dependent fashion. The inhibited gastric motility induced by acetazolamide was reversed by indomethacin but not by iodoacetamide. A highly significant relationship was found between the inhibitory effect of acetazolamide on the motor activity and the mucosal lesions (r +/- 0.8777, P < 0.01). We conclude that the mechanism mediating subcutaneous acetazolamide protection against 96
ethanolinduced gastric mucosal lesions is dependent on indomethacin- and independent of iodoacetamide sensitive mechanisms.
RESUMO
The aim of this study was to test the hypothesis that protective effect of subcutaneous acetazolamide, a carbonic anhydrase inhibitor, against ethanol-induced gastric mucosal damage is dependent on indomethacin- or iodoacetamide-sensitive mechanisms. In addition we studied the effects of acetazolamide on gastric motility and the influence of indomethacin and iodoacetamide on this parameter. Indomethacin (30 mg/kg) or iodoacetamide (100 ag/kg) was administered subcutaneously in doses that previously had been demonstrated to inhibit endogenous prostaglandins synthesis and gastric mucosal sulfhydryls respectively. At 30 min after these or control subcutaneous pretreatment, the rats were given subcutaneous acetazolamide or vehicle. Thirty min later 96
ethanol was administered orally and the rats were sacrificed 60 min after ethanol administration. The lesions of the gastric glandular mucosa were measured in length and width and expressed in square millimeters. Gastric motility was recorded by a balloon method. The results showed that neither indomethacin nor iodoacetamide aggravated ethanol-induced gastric mucosal damage. The protective effect of subcutaneous acetazolamide was suppressed by pretreatment with indomethacin but not with that of iodoacetamide. Acetazolamide inhibited gastric motility in a dose-dependent fashion. The inhibited gastric motility induced by acetazolamide was reversed by indomethacin but not by iodoacetamide. A highly significant relationship was found between the inhibitory effect of acetazolamide on the motor activity and the mucosal lesions (r +/- 0.8777, P < 0.01). We conclude that the mechanism mediating subcutaneous acetazolamide protection against 96
ethanolinduced gastric mucosal lesions is dependent on indomethacin- and independent of iodoacetamide sensitive mechanisms.