Protective and therapeutic effects of an extract mixture of alder tree, labiate herb, milk thistle green bean-rice bran fermentation, and turnip against ethanol-induced toxicity in the rat

An herbal extract mixture and yogurt added to the herbal extract mixture were tested for their protective and therapeutic effects on ethanol-induced liver injury. The herbal extract mixture, yogurt and commercial drugs were used for treatment for two weeks prior to administering a single oral dose of ethanol (3 g/kg body weight). The herbal extract mixture and yogurt added to the herbal extract mixture were found to provide protection against ethanolinduced toxicity comparable to the commercial drug treatment, according to the serum and histopathological analysis. It was also shown that co-treatment with herbal extract mixture and yogurt against a triple oral dose of ethanol (2 g/kg body weight, over one week) provided protection against ethanol toxicity. After the initial set of experiments, the herbal extract mixture and yogurt treatments were extended for three more weeks. When compared to the positive control, further treatment with both the herbal extract and yogurt significantly reduced liver injury and resulted in a lower grade of lipid deposition.

Effect of lecithin with vitamin-B complex and tocopheryl acetate on long-term effect of ethanol induced immunomodulatory activities.

The alcoholic liver disease usually causes overall immunological alterations which might be attributed to hepatic disease, to ethanol action, and/or to malnourishment. In the present study, efficacy of lecithin with vitamin-B complex to treat ethanol induced immunomodulatory activity was compared with the effect of lecithin alone and tocopheryl acetate (vitamin E). Ethanol (1.6 g/kg body wt/day for 12 weeks) exposure increased thiobarbituric acid reactive substance (TBARS) level, while decreased superoxide dismutase (SOD) activity and reduced glutathione (GSH) content in whole blood hemolysate of 8-10 week-old male BALB/c mice (weighing 20-30 g). The activities of transaminase (AST and ALT) enzymes, interleukin (IL)-10 and gamma interferon (IFN-gamma) elevated, while IL-2 and IL-4 reduced in mice serum due to ethanol exposure. These suggested that oxidative stress and immunomodulatory activities were interdependent and associated with ethanol induced liver damage. Lecithin treatment significantly reduced AST (32.44%), ALT (32.09%), IL-10 (25.63%) activities and TBARS content (12.76%) compared to ethanol treated group. However, lecithin with vitamin-B complex treatment, significantly reduced AST (62.83%); ALT (61.96%); IL-10 (35.88%); IFN-gamma (22.55%) activities and TBARS content (31.58%), while significantly elevated GSH content (36.49%) and SOD activity (61.21%). Tocopheryl acetate treatment significantly reduced AST (62.83%); ALT (61.54%); IL-10 (36.35%): IFN-gamma (23.28%) activities and TBARS content (35.84%). while significantly elevated GSH content (28.76%) and SOD activity (62.42%) compared to ethanol treated group. These findings persuasively argued that lecithin with vitamin-B complex was a new promising therapeutic approach in controlling ethanol induced immunomodulatory activities involving liver damage processes. Prevention of oxidative stress with correction of nutritional deficiency caused alteration in the ethanol-induced immunomodulatory activities and associated liver diseases.

Protective effect of testosterone against alcohol and paracetamol induced hepatotoxicity in rats.

Chronic ethanol and paracetamol consumption, both individually and in combination, caused hepatic changes in rats. Treatment of testosterone (2.5 mg/kg body wt.) to the alcoholic and paracetamol administered rats showed decreased activities of serum transaminases, serum acid and alkaline phosphatases, and decreased levels of hepatic triglycerides, cholesterol and free fatty acids. Concentration of the lipid peroxidation product-malondialdehyde was significantly decreased in the liver after testosterone treatment in alcohol and paracetamol administered groups. Histopathological observations further confirm that testosterone could offer protection against alcohol and paracetamol induced damage to liver in animals.

Blocking of alcohol-induced effects on synthesis and secretion of apo B containing lipoproteins by substituting sardine oil in the diet.

The effect of substitution of fish oil in the diet on the alcohol-induced changes in the metabolism of very low density lipoprotein (VLDL) by primary cultures of rat hepatocytes has been studied. Rats fed groundnut oil diet or sardine oil diet were given alcohol (3 g/kg) for 4 weeks. Substitution of fish oil for groundnut oil in the diet blocked the hypertriglyceridemia and hyperlipoproteinemia caused by alcohol. Enhanced incorporation of [3H]leucine into apo B secreted into the medium and [14C]acetate into lipids associated with secreted VLDL indicated an increased rate of synthesis of apo B containing lipoproteins by hepatocytes from livers of rats receiving alcohol. Fish oil in the diet reduced incorporation of [3H]leucine into apo B and that of [14C]acetate into lipids indicating a lower rate of synthesis of apo B containing lipoproteins. Pulse chase experiments confirmed the above observation. Thus it is suggested that fish oil in the diet prevents hyperlipoproteinemia caused by alcohol possibly by reducing the synthesis and secretion of VLDL by liver.

Protective effect of propranolol on ethanol-induced gastric lesions in rats: probable mechanism of action.

The non-selective beta-adrenoceptor antagonist, propranolol, has been reported to protect against gastric injury in mice, an effect only partly due to prostaglandin release. This study was designed to confirm the gastric cytoprotective effect of propranolol in another species of animal, the rat, and investigate further its mechanism of action. Our results show that propranolol prevents both ethanol-induced gastric lesions as well as ethanol-induced contraction of the circular muscle of rat fundic strip. The local anaesthetic, lignocaine also inhibited the effect of ethanol on circular muscle. However, timolol, another non-selective beta-adrenoceptor antagonist, failed to produce such an action. The effect of propranolol was abolished by the cyclooxygenase inhibitor, indomethacin and a high dose of the guanylate cyclase inhibitor, methylene blue. The results suggest that in addition to prostaglandins, endogenous nitric oxide and the membrane stabilising action of propranolol may also be involved in its gastroprotective action.

Rol de proton H+ y del bicarbonato en la citoproteccion gastrica adaptativa / Role of the H+ proton and bicarbonate in the adaptative gastric cytoprotection

En ratas Wistar se estudió el mecanismo no conocido de la citoprotección gástrica adaptativa, inducida por etanol al 20% y posterior injuria con etanol al 70%. El pretratamiento con Indometacina o Cl2 Hg no impidió la citoprotección gástrica adaptiva, indicando que en su mecanismo no participan ni las PGs endógenas, ni el mucus gástrico, respectivamente. En cambio, el pretratamiento con Ranitidina bloqueó y aun agravó las lesiones gástricas inducidas por el etanol -etanol; por el contrario, dicho fenómeno anterior fue revertido por el etanol al 20% acidificado. Se concluyó que la retrodifusión de H+ y el bicarbonato juegan roles importantes en el mecanismo de la citoprotección gástrica adaptativa

Indomethacin affects the development of tolerance to ethanol-induced diuresis

The present study analyzes the effects of indomethacin on the development of tolerance to the diuretic effect of ethanol. Male Wistar rats were with ethanol (2gKg-1 day-1) over a period of 4 weeks and the effect of ethanol on diuresis was assessed weekly. A significant tolerance to the diuretic effect of ethanol was detected after 3 weeks of treatment. However, rats treatment simultaneously with ethanol plus indomethacin (5mg/Kg, ip,, on alternate days) showed no tolerance to ethanol even after 4 weeks of treatment. The fact that indonethacin prevented the development of tolerance to the diuretic effect of ethanol but no influence on diuresis per se suggests that prostaglandins play a significant role in the mechanisms of tolerance to ethanol

Effect of milrinone on ethanol and halothane induced cardiodepression

Se estudió el efecto inotrópico de milrinona en preparaciones de corazón aislado de rata y de gato. En aurícula de rata con latido espontáneo se observó un efecto inotrópico positivo inicial dosis-dependiente, con aumento máximo en la tensión desarrolada (TD) de +26.5 ñ 2.8% con la dosis de 25 microng/ml y un aumento máximo de la frecuencia espontánea de 60 ñ 6% con la dosis de 80 microng/ml. Sin embargo, en aurícula de rata elétricamente dirigida, el aumento máximo de TD fue de +39.2 ñ 3.4%. La diferencia entre ambas preparaciones puede ser consecuencia del fenómeno de la escalera negativa que limita el aumento en TD en aurícula de rata con latido espontáneo. En aurícula aislada de gato eléctricamente dirigida, el efecto inotrópico positivo de milrinona se inició con la dosis de 0.5 microng/ml y el efecto máximo (36% de aumento en TD) se obtuvo con la dosis de 8 microng/ml. En músculo papilar de gato la relación dosis-respuesta se desplazó hacia arriba y hacia la ezquierda si se compara con preparaciones de aurícula de rata, y el aumento máximo de la TD fue de alrededor de 90%. En preparaciones de aurículas aisladas de rata el etanol (22 y 44 mM) produjo una significativa disminución de la TD dosis-relacionada, que fue revertida por milrinona y su relación dosis-efecto fue similar tanto en presencia como en ausencia de etanol. En músculo papilar aislado de gato, el etanol (rr mM) produjo una disminución de la TD de 15.1 ñ 1.8%. Milrinona en concentraciones bajas de hasta 8 microng/ml prod

Efecto citoprotector de enprostil sobre la mucosa gástrica dañada con etanol en la rata. Estudio con citoquímica de alta resolución y microscopía electrónica de barrido / Protective effect of enprostil on the cells of gastric mucosa demaged by ethanol in the rat. High resolution cytochemical scanning elelctron microscopy study

El objeto de este trabajo fue analizar la partcipación de la capa de glicoproteínas de la membrana plasmática en el efecto citoprotector de un análogo de la PGE, utilizando como modelo el estómago de la rata irritado con etanol. A un grupo de ratas Long-Evans previamente tratadas con Enprostil se les instiló 0.5 ml. de etanol absoluto por vía oral. Los animales fueron sacrificados a los 0,30 y 60 minutos y los estómagos fueron estudiados con microscopía de luz, electrónica de transmisión utilizando rojo de Rutenio como marcador y microscopía electrónica de barrido. Un grupo de ratas sólo recibió etanol. La mucosa gástrica de este último grupo reveló hiperhemia y necrosis con disociación y ausencia de la capa glicoproteica. Estos cambios no se observaron en los estómagos del grupo tratado cocn el análogo de la prostaglandina en donde estacó la capa de rojo de Rutenio. Parece ser que el efecto citoprotector de estas sustancias incluye un efecto inductor sobre la producción o secreción de glicocproteínas que se correlacionó con la microscopía electrónica de barrido

Posible relación entre un factor endógeno y la resistencia del duodeno al cáncer / Possible relation between an endogen factor and the cancer duodenal resistance

En el presente trabajo se investigó si existe en el duodeno de rata alguna sustancia con efecto sobre el desarrollo del carcinosarcoma de Walter, que seria la responsable del diferente comportamiento fisiopatológico de este tejido frente a las celulas neoplásicas. Después de evidenciar la presencia de ese factor actividad antitumoral, se determimino sus propiedades farmacológicas y químicas y se estudio su presencia en distintas secciones del tracto gastrointestinal y en otros tejidos del mismo animal y en tejido duodenal de otras especies