Ethanol and the antioxidant defense in the gastrointestinal tract.

Ethanol is known to have profound actions on the gastrointestinal tract. The present study was undertaken to examine the effects of ethanol on some of the natural antioxidant defensive enzymes in the gastrointestinal tract; the activities of these enzymes in the liver and the brain were also measured for comparison with those in the gastrointestinal tract. Oral administration of absolute ethanol induced severe gastric mucosal lesions and also damage in the small intestine, however the total superoxide dismutase was unaffected in the tissues measured. The glucose-6-phosphate dehydrogenase activity was reduced only in the stomach while the total glutathione was elevated in the small intestinal mucosa. The catalase activities were activated in the stomach, small and large intestines, and brain, but not in the liver which contained the highest concentration of the enzyme. The present findings indicate that endogenous hydrogen peroxide may be an important damaging agent towards biomolecules in different organs and the removal of this by catalase represents an important defensive mechanism against ethanol toxicity.     

Prophylactic and curative effects of Bacopa monniera in gastric ulcer models.

Bacopa monniera Wettst. (BM, syn. Herpestis monniera L; Scrophulariaceae), is an Ayurvedic drug used as a rasayana. Its fresh juice was earlier reported to have significant antiulcerogenic activity. In continuation, methanolic extract of BM (BME) standardized to bacoside-A content (percentage-38.0 ± 0.9), when given in the dose of 10–50 mg/kg, twice daily for 5 days, showed dose-dependent anti-ulcerogenic on various gastric ulcer models induced by ethanol, aspirin, 2 h cold restraint stress and 4 h pylorus ligation. BME in the dose of 20 mg/kg, given for 10 days, twice daily showed healing effects against 50% acetic acid-induced gastric ulcers. Further work was done to investigate the possible mechanisms of its action by studying its effect on various mucosal offensive acid-pepsin secretion and defensive factors like mucin secretion, mucosal cell shedding, cell proliferation and antioxidant activity in rats. BME 20 mg/kg showed no effect on acid-pepsin secretion, increased mucin secretion, while it decreased cell shedding with no effect on cell proliferation. BME showed significant antioxidant effect per se and in stressed animals. Thus, the gastric prophylactic and curative effects of BME may be due to its predominant effect on mucosal defensive factors.     

Prophylactic and curative effects of Bacopa monniera in gastric ulcer models

Bacopa monniera Wettst. (BM, syn. Herpestis monniera L; Scrophulariaceae), is an Ayurvedic drug used as a rasayana. Its fresh juice was earlier reported to have significant antiulcerogenic activity. In continuation, methanolic extract of BM (BME) standardized to bacoside-A content (percentage-38.0 ± 0.9), when given in the dose of 10–50 mg/kg, twice daily for 5 days, showed dose-dependent anti-ulcerogenic on various gastric ulcer models induced by ethanol, aspirin, 2 h cold restraint stress and 4 h pylorus ligation. BME in the dose of 20 mg/kg, given for 10 days, twice daily showed healing effects against 50% acetic acid-induced gastric ulcers. Further work was done to investigate the possible mechanisms of its action by studying its effect on various mucosal offensive acid-pepsin secretion and defensive factors like mucin secretion, mucosal cell shedding, cell proliferation and antioxidant activity in rats. BME 20 mg/kg showed no effect on acid-pepsin secretion, increased mucin secretion, while it decreased cell shedding with no effect on cell proliferation. BME showed significant antioxidant effect per se and in stressed animals. Thus, the gastric prophylactic and curative effects of BME may be due to its predominant effect on mucosal defensive factors.     

Effect of standardized extract of Ocimum sanctum Linn. on gastric mucosal offensive and defensive factors

The standardized methanolic extract of leaves of O. sanctum (OSE; eugenol content 5%) given in doses of 50-200 mg/kg, orally, twice daily for five days showed dose-dependent ulcer protective effect against cold restraint stress induced gastric ulcers. Optimal effective dose (100 mg/kg) of OSE showed significant ulcer protection against ethanol and pyloric ligation-induced gastric ulcers, but was ineffective against aspirin-induced ulcers. OSE significantly healed ulcers induced by 50% acetic acid after 5 and 10 days treatment OSE (100 mg/kg) significantly inhibited the offensive acid-pepsin secretion and lipid peroxidation and increased the gastric defensive factors like mucin secretion, cellular mucus, and life span of mucosal cells and had antioxidant effect, but did not induce mucosal cell proliferation. The results indicate that the ulcer protective and healing effects of OSE may be due to its effects both on offensive and defensive mucosal factors.     

Effects of ethanol on the activity of brain enzymes

Ethanol alters, in a selective manner, the activity of several membrane-bound enzymes in the central nervous system (CNS) which are important for neuronal transmission of information. Ethanol inhibits Na+/K+-transporting ATPase activity, while adenylate cyclase (AC) activity is stimulated by ethanol added in vitro. Ethanol's effects on AC activity are mediated primarily via effects on proteins that regulate AC activity. Ethanol has selective effects on monoamine oxidase activity, in that the B form of the enzyme is more sensitive to inhibition by ethanol added in vitro. The selective effects of ethanol on different membrane-bound CNS enzymes may result from differing membrane lipid microenvironments of the enzymes, or from differences in the enzyme proteins per se.     

Effect of Convolvulus pluricaulis Chois on gastric ulceration and secretion in rats

Convolvulus pluricaulis is an indigenous plant commonly mentioned in Ayurveda, an ancient system of Indian medicine, as a rasayana which is mainly advocated for use in rejuvenation therapy. The present study was conducted to evaluate the potential anti-ulcerogenic effect of juice of fresh whole plants of C. pluricaulis (CPJ) against various experimental gastric ulcer models induced by ethanol, aspirin, 2 hr cold restraint stress and 4 hr pyloric ligation in rats. The drug was given orally twice daily for five days in the doses of 375 and 750 mg/kg body weight. CPJ showed anti-ulcerogenic effect at both doses in all the experimental gastric ulcer models and was comparable to the reference drug sucralfate (250 mg/kg). Gastric juice secretion and mucosal studies were undertaken to find out the possible mechanism of action of antiulcer effect by studying its effects both on offensive and defensive mucosal factors. The antiulcerogenic effect of CPJ was found to be due to augmentation of mucosal defensive factors like mucin secretion, lifespan of mucosal cells and glycoprotiens rather than on the offensive factors like acid-pepsin.     

Ethanol feeding to rats reversibly decreases hepatic carnitine palmitoyltransferase activity and increases enzyme sensitivity to malonyl-CoA

The effects of prolonged ethanol feeding on both carnitine palmitoyltransferase I activity and enzyme sensitivity to inhibition by malonyl-CoA were studied in rat liver, heart, skeletal muscle and kidney cortex mitochondria. Heart and skeletal muscle enzymes showed the highest specific activity and sensitivity to malonyl-CoA. Carnitine palmitoyltransferase I in extrahepatic tissues showed no changes on ethanol feeding. Only the liver enzyme activity was altered after long term ethanol administration, by suffering a progressive decrease in activity and a parallel increase in sensitivity to malonyl-CoA. These alterations reversed after 10 days of ethanol withdrawal. These results are discussed in relation to the control of carnitine palmitoyltransferase I and the effects of ethanol on fatty acid metabolism.     

The phytotoxic effect of exogenous ethanol on Euphorbia heterophylla L.

This study investigated the effects of exogenously applied ethanol on Euphorbia heterophylla L., a troublesome weed in field and plantation crops. Ethanol at concentrations ranging from 0.25 to 1.5% caused a dose-dependent inhibition of germination and growth of E. heterophylla. Measurements of respiratory activity and alcohol dehydrogenase (E.C. 1.1.1.1) activity during seed imbibition and initial seedling growth revealed that ethanol induces a prolongation of hypoxic conditions in the growing tissues. In isolated mitochondria, ethanol inhibited the respiration coupled to ADP phosphorylation, an action that probably contributed to modifications observed in the respiratory activity of embryos. A comparison of the effects of methanol, ethanol, propanol and acetaldehyde on germination and growth of E. heterophylla indicates that alcohol dehydrogenase activity is required for the observed effects, with the conversion of ethanol to acetaldehyde playing a role in the ethanol-induced injuries.     

Modulation of NK cell activity by moderate intensity endurance training and chronic ethanol consumption.

Chronic ethanol consumption can suppress natural killer (NK) cell activity. Exercise after ethanol administration may enhance blood ethanol clearance, which may benefit the immune response. This study examined the effects of moderate intensity endurance training and chronic ethanol consumption (20% wt/vol) on splenic NK cell activity. Mice were assigned to one of four groups: sedentary, water drinking (SED-H2O); sedentary, ethanol consuming (SED-EtOH); trained, water drinking (TR-H2O), and trained, ethanol consuming (TR-EtOH). TR groups ran 60 min/day, 5 days/wk, at 12 m/min for 10 wk. Mice were killed 48 h after exercise. Baseline NK cell activity was suppressed 30% in TR and EtOH groups compared with SED-H2O controls. Activation with recombinant human interleukin-2 increased cytolytic activity in all groups four- to fivefold. These results indicate that training did not abrogate the effects of chronic ethanol consumption on NK cell activity. Furthermore, moderate endurance training may contribute to suppressed nylon wool-enriched NK cell activity in murine splenocytes for as long as 48 h after exercise.     

Contributions of female oviposition patterns and larval behavior to group defense in conifer sawflies (hymenoptera: diprionidae)

We studied the effects of adult oviposition and larval interactions on the defensive potential of gregarious behavior in conifer sawflies. Aggregation size and distribution initially reflected adult host plant selection and oviposition behavior. The contagious distribution of egg clusters resulted in part from the utilization of individual trees by multiple females, and of single host shoots by several females. Trees with the greates degree of prior defoliation received the most eggs, even though the potential for larval crowding made resource depletion possible. Foliar monoterpene and nitrogen contents explained only a small proportion of variability in female host utilization. Conifer needle architecture restricted the size of larval subgroups within aggregations, and limited the degree of defensive cohesiveness between subgroups. Subgroup turnover was frequent and independent of local food depletion. Risk of predation from wood ants varied with larval aggregation size and predator foraging level. When ant activity was high, large aggregations suffered greater numerical losses, but showed lower per capita predatory risk, than small groups. Results suggest that female oviposition patterns are influenced in part by the defensive benefits gained by offspring in large aggregations. Against ants, dilution effects and defensive synchrony due to gregariousness contribute to the overall antipredator strategy of sawfly larvae.     

Effect of ethanol on ATP-hydrolase activity of myometrial actomyosin

In order of estimating some regularities of ethanol effective action on the uterus smooth muscles contractile proteins the effects of spiritus introduced into incubation medium on myometrium actomyosine ATP-hydrolase activity and superprecipitation was studied. ATP-hydrolase activity was displayed as more sensitive to ethanol action; its dependence on ethyl spiritus concentration had three-phase character expressed in two inhibiting and one activating sites. While defining the kinetic parameters of ATP hydrolysis reaction catalysed by uterus myometrium the correlation between inhibition the ATP-hydrolase activity of myometrium contractile complex under introducing into incubation medium 2% ethanol and decreasing the affinity of actomyosine to Mg2+ was made; the highest activating effect of ethanol on ATP-hydrolase activity of actomyosine complex in the presence of 8% ethanol correlated with increasing the affinity of actomyosine to Mg2+ and ATP.     

Conditioned reflex and electrical activities of the hippocampus during the random use of heterogeneous triggering stimuli

In dogs with electrodes chronically implanted in the hippocampus, the conditioned activity, heart rate frequency and spectral characteristics of the hippocampal theta-rhythm were studied in conditions of irregular presentation after a preparatory stimulus now of alimentary and now of defensive triggering conditioned stimuli. It is shown that uncertainty of alimentary or defensive reinforcement is a stronger emotiogenic factor than the action of the triggering defensive conditioned stimulus. Changes in electrical hippocampal activity and autonomous activity depend, along with other factors, on forecasted volume of the forthcoming motor activity. The speed of instrumental conditioned reflexes formation correlates with the hippocampal theta-rhythm frequency, typical for the given animal.     

Participation of pentagastrin and oxytocin in organizing neural activity of the dorsal hippocampus during result- and conflict-oriented feeding behavior in rabbits

Single unit activity of CA3 dorsal hippocamp has been registered in free moving rabbits. The influence of microiontophoretic application of pentagastrin and oxytocin on neuronal involvement into feeding or defensive behaviour has been studied. The change of the dominant feeding motivation to defensive was shown to cause resettings in the typical feeding activity of most neurons. Microiontophoretic application of pentagastrin induces typical feeding activity even if rabbits demonstrate defensive behaviour. It is believed that pentagastrin presence in perineuronal area leads to the involvement of most hippocampal neurons into the organization of the feeding behaviour.     

Effects of alcohol (ethanol) on the fetus

Alcohol (ethanol) use during pregnancy can produce a wide spectrum of effects in the developing embryo/fetus that are dependent on the maternal drinking pattern. The effects of chronic ethanol exposure on the developing conceptus are reviewed with primary focus on ethanol teratogenesis, manifesting in the human as the fetal alcohol syndrome or fetal alcohol effects. The effects of acute ethanol exposure on the near-term fetus are described, including suppressed fetal breathing movements, electrocorticographic (ECoG) activity and electrooculographic (EOG) activity. The ethanol-induced suppression of fetal breathing movements is a very sensitive index of acute exposure of the near-term fetus to ethanol, and appears to involve a direct mechanism of action rather than an indirect mechanism involving suppression of electrocortical activity. The disposition of ethanol and its pharmacologically active proximate metabolite, acetaldehyde, and the activity of alcohol dehydrogenase and aldehyde dehydrogenase in the near-term maternal-fetal unit are described, and a pharmacokinetic model is proposed. The effects of short-term ethanol exposure on the near-term fetus include the development of tolerance to the ethanol-induced suppression of fetal breathing movements, low-voltage ECoG activity and EOG activity. The development of tolerance occurs more rapidly to the latter two fetal biophysical activities. The mechanism of tolerance development appears to be pharmacodynamic (functional) in nature, as there is no increase in the rate of ethanol elimination from the maternal-fetal unit. The role of prostaglandins (PGs) in the mechanism of the ethanol-induced suppression of fetal breathing movements is described. In the near-term fetus, there is a direct relationship between fetal blood ethanol concentration and fetal plasma PGE2 concentration, and an inverse relationship between the incidence of fetal breathing movements and each of fetal plasma and fetal cerebrospinal fluid (CSF) PGE2 concentrations. Indomethacin, a PG synthetase inhibitor, selectively blocks and reverses the ethanol-induced suppression of fetal breathing movements. These data support the postulates that the ethanol-induced suppression of fetal breathing movements is mediated by increased PGE2 concentration in the near-term fetus and that the ability of indomethacin to antagonize the ethanol-induced suppression of fetal breathing movements is due to its biochemical action to decrease fetal PGE2 concentration.(ABSTRACT TRUNCATED AT 400 WORDS)     

Hepatoprotective effects of Liv-52 on ethanol induced liver damage in rats

The mechanism of protective effects of Liv-52, a multiherbal hepatoprotective drug, on ethanol induced hepatic damage has been investigated. The results indicate that Liv-52 treatment prevents ethanol induced increase in the activity of the enzyme gamma-glutamyl transpeptidase. Concomitantly there was also a decrease in ethanol accentuated lipid peroxidation in liver following Liv-52 treatment. The activity of antioxidant enzymes; superoxide dismutase, glutathione peroxidase and the levels of glutathione were decreased following ethanol ingestion. Liv-52 treatment was found to have protective effects on the activity of superoxide dismutase and the levels of glutathione. The results obtained from the study indicate hepatoprotective nature of Liv-52 which might be attributed to its ability to inhibit lipid peroxidation.     

Behavioural and toxic effects of termite defensive secretions on ants

ABSTRACT. The toxicity and biological activity of the defensive secretions of ten species of neotropical termites were examined by bioassay on two species of predatory ant. Pseudomyrmex termitarius (F. Smith) (Pseudomyrmecinae) was more susceptible to the effects of the secretions than Ectatomma sp. (Ponerinae). The bioassay results show a progression in the nature of termite chemical weaponry and in the potency of defensive secretions. The tacky secretions used by Coptotermes and Ruptitermes are simply adhesive, entangling agents with no apparent toxic or pheromonal properties. The secretion of Syntermes calvus Emerson serves as a wound-active poison with little topical activity, while those of Armitermes spp. are repellent to ants and show activity as topical poisons. The secretions used by Nasutitermes spp. combine adhesive, entangling properties with the toxicity of a topically-active poison, and are effective also as ant-repellents.     

Liver alcohol dehydrogenase activity in the female rat: Effects of ovariectomy and estradiol administration

The effects of ovariectomy and administration of estradiol on the activity of liver alcohol dehydrogenase and on the rate of ethanol elimination were determined in female Sprague-Dawley rats. The activity of the enzyme and the rates of ethanol elimination in the female sham-operated animals were higher than obtained previously in male rats of the same age. Ovariectomy had no effect on liver alcohol dehydrogenase and on rates of ethanol elimination. Estradiol administration resulted in an increase in liver weight and in total liver alcohol dehydrogenase activity per animal in sham-operated but not in ovariectomized animals. The increase in enzyme activity after estradiol administration in sham-operated animals was not associated with a significant increase in the rate of ethanol elimination, suggesting that the enzyme activity in female rats is not rate-limiting in in vivo ethanol oxidation.     

Effects of Ca2+ on catalytic activity and conformation of trypsin and alpha-chymotrypsin in aqueous ethanol

The effects of calcium ions on the conformation and catalytic activity of trypsin and alpha-chymotrypsin were studied in aqueous ethanol. The activity of alpha-chymotrypsin was practically lost within 10 min in the presence of 60% ethanol while trypsin preserved about 40% of its original activity even in 85% ethanol at pH 3. The catalytic activity of alpha-chymotrypsin did not decrease in the presence of 1.2M CaCl2 and 0.6M CaCl2 with trypsin in ethanolic solvent. In the latter case an activation of enzyme was observed. The stabilizing effects of calcium ions were accompanied by an increase in the helical content in both enzymes, as followed by circular dichroism measurements.