Chronic Ethanol Administration In Rats Research Articles

Cerebrolysin attenuates ethanol-induced spatial memory impairments through inhibition of hippocampal oxidative stress and apoptotic cell death in rats.

The present study investigates the potential neuroprotective effect of cerebrolysin (CBL), a combination of neurotrophic factors, on the cognitive and biochemical alterations induced by chronic ethanol administration in rats. The animals were divided into five groups as follows: control; ethanol (4g/kg, for 30 days) plus normal saline (Ethanol+NS); ethanol plus CBL 1mL/kg (Ethanol+CBL 1), ethanol plus CBL 2.5mL/kg (Ethanol+CBL 2.5); and ethanol plus CBL 5mL/kg (Ethanol+CBL 5). The Morris water maze (MWM) test was performed to assess cognitive impairment. The status of the lipid peroxidation marker MDA, antioxidant capacity, as well as alterations of the apoptotic factors such as Bcl-2, BAX, and cleaved caspase-9 and -3, were evaluated in the hippocampus. The results showed that CBL treatment not only normalized the increased MDA levels in the alcoholic rats and enhanced antioxidant defense, but also reduced the Bax/Bcl-2 ratio and cleaved caspase-9 and -3 in the hippocampus. These results were parallel with improvement in spatial memory performance in the MWM test. The findings of the present study provide evidence for the promising therapeutic effect of CBL in chronic ethanol consumption through counteracting oxidative stress and apoptosis markers.

The effect of long-term ethanol feeding on Brucella melitensis infection of rats.

The adverse effects of ethanol on Brucella melitensis have not been studied previously. In this study, a new model of B. melitensis infection was used in the setting of chronic ethanol administration in rats. It was found that the chronically ethanol-receiving rats exposed to B. melitensis infection had significantly greater numbers of B. melitensis in their spleen and liver than the rats in the control group.

Stress Proteins and SH-Groups in Oxidant-Induced Cellular Injury After Chronic Ethanol Administration in Rat

It is generally agreed that lipid peroxides play an important role in the pathogenesis of ethanol-induced cellular injury and that free sulfhydryl groups are vital in cellular defense against endogenous or exogenous oxidants. It has been observed that oxidative stress induces the synthesis of the 70-kDa family of heat-shock proteins (HSPs). Induction of HSPs represents an essential and highly conserved cellular response to a variety of stressful stimuli. In the present study we measured in various brain areas and in liver the intracellular levels of HSP70 proteins, sulfhydryl groups and the antioxidant enzyme status after chronic administration of mild intoxicating doses of ethanol to rats. Expression of HSP70 in response to alcohol administration was particularly high in the hippocampus and striatum. In these brain areas, the increase in HSP70 protein levels occurred in absence of significant changes of antioxidant enzyme activities and was correlated with a marked depletion of intracellular bound thiols and with a decreased susceptibility to lipid peroxidation. Lower levels of HSP70 induction were found in cortex and cerebellum and were associated to decreases in SOD and CAT enzyme activities, with a lower depletion of protein bound thiols and with an increased susceptibility to lipid peroxidation. This study agrees with our previous results performed on acute alcohol intoxication and supports the hypothesis that HSP70 induction protects the different brain areas against oxidative stress.

Influence of an n-6 polyunsaturated fatty acid-enriched diet on the development of tolerance during chronic ethanol administration in rats.

This study investigates the effects of n-6 polyunsaturated fatty acids (PUFAs), in the form of dietary Evening Primrose Oil (EPO) and safflower oil, on the development of tolerance to ethanol. The degree of fluorescence polarization of the fluoroprobes DPH, PROP-DPH, and TMA-DPH in isolated cortical synaptosomal membranes was measured. In addition, the development of tolerance, as shown by changes in synaptosomal membrane fluidity after an acute in vitro ethanol challenge, was also determined after 20 weeks of ethanol administration, either alone or together with a PUFA-enriched diet. Although the administration of EPO-enriched diet did not significantly render the inner core of the cortical synaptosomal membrane tolerant to the acute ethanol challenge, concomitant administration of ethanol and EPO was found to increase further the rigidity and tolerance to the acute ethanol challenge in the inner core. Chronic administration of safflower oil, which lacks gamma-linolenic acid (18:3, n-6) but like EPO contains linoleic acid, either alone or together with chronic ethanol had no effect on synaptosomal membrane fluidity after an acute ethanol challenge. The results suggest that gamma-linolenic acid or its metabolites may have an important role to play in the development of tolerance to chronic ethanol.

A modified liquid diet of chronic ethanol administration: Validation by ethanol withdrawal syndrome in rats

The validity of a modified liquid diet prepared from cow's milk, 7.2% ethanol, vitamin A and sucrose mixture has been investigated for chronic ethanol administration in rats. The rats fed by the modified liquid diet lost 3.8% of their body weight along 20 days. The mean ethanol consumption was in the range of 12.6 to 17.6 g kg −1 day −1. The blood ethanol level just before the withdrawal of ethanol was found to be 301.38±36.68 mg dl −1. A severe ethanol withdrawal syndrome was observed after 20-day exposure to ethanol in the modified liquid diet. The results suggest that the modified liquid diet can be used satisfactorily for chronic ethanol administration in rats.

Delayed ethanol effects on physiological and behavioral indices in the rat

The purpose of this project was to examine time-dependent initial and delayed behavioral and physiological effects of acute and chronic ethanol administration in rats. Experiment 1 compared the 24-h changes in temperature (rectal probe), activity (open field), and analgesia (tail-flick test) induced by an acute 4-g/kg dose of ethanol before and after a chronic regimen of ethanol. Initial hypothermic, hypoactivity, and analgesic effects were found, but no delayed secondary effects were evident and tolerance occurred only for the analgesic measure. Experiment 2 examined dose-dependent, 48-h changes in temperature and activity (monitored simultaneously and continuously via implanted telemetry sensors) before and after a daily regimen of ethanol injections. Acute ethanol produced dose-dependent initial hypothermic and hypoactivity effects followed by a delayed hyperthermic effect. Following the chronic ethanol regimen, tolerance to all effects was evident. The results were discussed in terms of methodological differences in the two experiments and the possible basis for the delayed ethanol effects. There is a strong suggestion that the secondary hyperthermic effect represents not a rebound, homeostatic phenomenon restricted to the temperature system, but rather an “artifact” due to a disruption of the circadian rhythm, resulting in an absence of the normal reduction in activity seen during the light cycle.

Blood and liver lipid peroxide status after chronic ethanol administration in rats

During the last decades a vast number of reports have aimed at elucidating the mechanisms behind alcohol-related organ injury, but the manner in which ethanol induces, e.g., liver damage is still an enigma. Increased oxidative stress has been put forward has been put forward as one possible mechanism behind alcohol-related tissue damage. This paper focuses on the effect of chronic ethanol consumption on antioxidant status and lipid peroxide levels in blood and liver of rats. Alcohol was given twice daily in a total dose of 5 g ethanol/kg body wt. per day divided into two 2.5 g ethanol/kg body wt. doses as a 50% water solution, by gavage over 4 weeks. Chronic ethanol ingestion led neither to a significant change in lipid peroxide formation nor to a significant change in enzymatic antioxidant activities. Only concentrations of oxidized glutathione and of other non-enzymatic antioxidants such as vitamin E showed a tendency to decrease after alcohol application. The data presented could serve to emphasize no involvement of free radical-induced lipoperoxidation in the pathogenesis of ethanolic liver diseases.

The changes in sulfhydryl compounds in plasma, liver and brain after acute and chronic ethanol administration in rats

The content of sulfhydryl compounds in proteins and non-proteins of plasma, liver and brain after acute and chronic ethanol administration was investigated in rats. After ethanol ingestion for 4 weeks (6 g/kg, day 30% w/ v) significant changes were observed in plasma proteins and in liver proteins and non-proteins. In brain proteins and non-proteins we did not find any changes in sulfhydryl compounds content after acute and chronic ethanol administration.

An interdisciplinary approach to drug tolerance

The purpose of this project was to examine time-dependent initial and delayed behavioral and physiological effects of acute and chronic ethanol administration in rats. Experiment 1 compared the 24-h changes in temperature (rectal probe), activity (open field), and analgesia (tail-flick test) induced by an acute 4-g/kg dose of ethanol before and after a chronic regimen of ethanol. Initial hypothermic, hypoactivity, and analgesic effects were found, but no delayed secondary effects were evident and tolerance occurred only for the analgesic measure. Experiment 2 examined dose-dependent, 48-h changes in temperature and activity (monitored simultaneously and continuously via implanted telemetry sensors) before and after a daily regimen of ethanol injections. Acute ethanol produced dose-dependent initial hypothermic and hypoactivity effects followed by a delayed hyperthermic effect. Following the chronic ethanol regimen, tolerance to all effects was evident. The results were discussed in terms of methodological differences in the two experiments and the possible basis for the delayed ethanol effects. There is a strong suggestion that the secondary hyperthermic effect represents not a rebound, homeostatic phenomenon restricted to the temperature system, but rather an “artifact” due to a disruption of the circadian rhythm, resulting in an absence of the normal reduction in activity seen during the light cycle.

Adrenocortical response to acute and chronic ethanol administration in rats.

Acute ethanol administration (2 g/kg IP) induced a significant rise in serum corticosterone levels which seemed to be related to blood ethanol concentration. Chronic ethanol administration, in the form of a liquid diet for 16 or 30 days, did not alter the levels of serum corticosterone. Chronic treatment of rats with a liquid diet containing ethanol resulted in the development of tolerance.

Potentiation of halothane hepatotoxicity by chronic ethanol administration in rat: An animal model of halothane hepatitis

To determine if chronic ethanol administration modifies the effect of halothane on the liver, fourteen male Wistar rats were pair-fed nutritionally adequate liquid diets containing either ethanol (36% of calories) or isocaloric carbohydrate (controls) for 6 weeks. After halothane anesthesia of these animals under different oxygen concentration, the livers were examined light microscopically as well as biochemically. The livers from rats fed ethanol which received halothane at low oxygen concentration showed multifocal or patchy necrosis primarily in the centrilobular regions with parenchymal lipid accumulation, whereas no such lesions were not observed in pair-fed controls. Hepatic necrosis was also seen after halothane anesthesia even at ambient oxygen concentrations, although the degree of necrosis was much milder. Hepatic microsomal cytochrome P450 content was increased by 30% after ethanol but was decreased following halothane anesthesia. These data suggest that halothane is hepatotoxic to liver of rats chronically pretreated with ethanol, especially under hypoxic condition.

Studies on the hepatic accumulation of triglyceride induced by chronic ethanol administration in rats fed with various diets.

Studies on the hepatic accumulation of triglyceride induced by chronic ethanol administration in rats fed with various diets.

Intestinal thiamin transport: effect of chronic ethanol administration in rats

The effect of chronic ethanol treatment on intestinal thiamin transport was studied. Rats were fed the De Carli-Lieber ethanol diet for 6 to 8 weeks and 14C-thiamin uptake and exit from enterocytes were measured in inverted gut sacs and correlated with basolateral membrane Na-K ATPase activity. Thiamin transport rate and Na-K ATPase activity were not affected in chronic ethanol-treated rats compared to pair-fed controls. Ethanol concentrations in gut lumen and plasma at time of study were 39.3 ± 15.3 and 40.2 ± 19.4 mg/100 ml, respectively, although higher levels were noted at other times. Tissue thiamin pyrophosphate remained normal. In contrast, ethanol-treated rats given intragastrically an extra dose of ethanol 250 mg/100 g of body weight one hour before study showed a decrease in cellular exit of 0.2 and 0.5 µm thiamin to 44 and 56% of control, respectively (P < 0.025) and of Na-K ATPase to 32% of control (P < 0.001) when gut and plasma ethanol levels were 318.3 ± 38.7 and 185.0 ±8.7 mg/100 ml, respectively. These studies 1) confirm the inhibitory effect of ethanol on thiamin transport, 2) show that inhibition is dependent more on the ethanol concentration than on the duration of exposure to ethanol, and 3) suggest that thiamin malabsorption in this animal model may be intermittent. These findings may be relevant with referance to alcoholics with periodic binge drinking.