Luminal acid in water-inmersion stress and the antiulcer effect of axetazolamide in the rat gastric mucosa

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.

Mechanism of intragastric amoxicillin protection against 96 percent ethanol damage in rat stomach

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.

Thioctic acid protection against ethanol-induced gastric mucosal lesions involves sulfhydryl and prostagladin participation

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.

Thioctic acid protection against ethanol and indomethacin induced gastric mucosal lesions in rats

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.

Gastric mucosal protection by acetazolamide in rats. Roles of prostaglandins, sulfhydryls, and gastric motility

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.

Ulceras gastricas gigantes. / Giant gastric ulcers

Se efectuo estudio clinicopatologico de 43 ulceras gastricas gigantes tratadas en la division de Cirugia del Hospital Centenario, Rosario. Hemos verificado: 1) Importante perdida de peso corporal de los pacientes. 2) Alta incidencia en hemorragia, penetracion y perforacion (en peritoneo libre y en cubierta). 3) El 30% de la ulceras fueron pseudotumorales. 4) La incidencia de carcinoma fue del 7%. Se enfatizo la importancia de un diagnostico etiologico correcto para evitar la opcion de tratamiento erroneo