Chronic Ethanol Consumption In Rats Research Articles

Gut region-specific rearrangement of the cellular and subcellular compartments of nitric oxide synthase isoforms after chronic ethanol consumption in rats.

We recently provided evidence of cell-type-specific differences in the subcellular distributions of the three nitric oxide synthase (NOS) isoforms in the myenteric neurons, enteric smooth muscle cells and the capillary endothelium of the rat duodenum. We hypothesized that the presence of three NOS isoforms in the same type of cells with differences in subcellular compartmentalization might reflect a functional plasticity. Therefore, investigation of the possible rearrangement of cellular and subcellular NOS compartments in different gut segments following chronic ethanol treatment was the aim of this study. Rats were randomly divided into two groups and received water or 20% ethanol solution, preceded by short periods of adaptation with 10% and 15% ethanol. After 8 weeks, segments of duodenum, ileum and colon of the control and the alcohol-treated rats were processed for post-embedding immunohistochemistry and RT-PCR. The quantitative differences in the numbers of gold particles indicative of the different NOSs and their relative mRNA levels between the two experimental groups varied greatly, depending on the gut segment, and also on the cellular and subcellular compartments investigated. The chronic ethanol administration had the opposite effect on the quantitative distribution of the neuronal and endothelial NOS labelling gold particles in the different cellular compartments and resulted in subcellular rearrangement of NOS labels along the gastrointestinal tract. The intestinal region-specific rearrangement of the cellular and subcellular NOS compartments may possibly result in functional plasticity and help to maintain the optimum NO level under pathological conditions.

Effects of Lycii fructus Extracts on the Erectile Dysfunction by Chronic Ethanol Consumption in Rats

Erectile dysfunction (ED) is a highly prevalent disorder that affects millions of men worldwide. ED is now considered an early manifestation of atherosclerosis, and consequently, a precursor of systemic vascular disease. Lycii fructus extracts (LFE) were administered for 4 weeks to assess the improving effects on ED. Animals were divided into one normal group and four LFE-treated groups (0, 0.3, 0.6, and 1.2 g/kg). We induced ED in the study animals by oral administration of 20% ethanol instead of water everyday for 4 weeks. This study was designed to investigate the effects of LFE on the mRNA levels of inducible nitric oxide synthase (iNOS) and endothelial NOS (eNOS) expression; NO levels of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP); blood profile; and erectile response of the corpus cavernosum of the rat penis. The libido of the LFE-administered male rats was higher than that of the ethanol control group. The erectile response of the corpus cavernosum was restored after LFE administration, to a level similarto the normal group. In addition, the iNOS in the corpus cavernosum of the male rats administered LFE decreased. In contrast, compared to the control group, LFE-administered male rats showed increased eNOS, NO and cGMP levels in the corpus cavernosum. These results indicate that LFE effectively restored ethanol-induced ED in male rats.

Effects of male silkworm pupa powder on the erectile dysfunction by chronic ethanol consumption in rats

Erectile dysfunction (ED) is a highly prevalent disorder that affects millions of men worldwide. ED is now considered an early manifestation of atherosclerosis, and consequently, a precursor of systemic vascular disease. This study was designed to investigate the effects of male silkworm pupa powder (SWP) on the levels of nitric oxide synthase (NOS) expression, nitrite, and glutathione (GSH); lipid peroxidation; libido; and erectile response of the corpus cavernosum of the rat penis. We induced ED in the study animals by oral administration of 20% ethanol over 8 weeks. The SWP-treated male rats were divided into 3 groups that were orally administered 200, 400, and 800 mg/kg. The libido of the SWP-administered male rats was higher than that of the ethanol control group. In addition, the erectile response of the corpus cavernosum was restored in males on SWP administration, to a level similar to that of the normal group without ED. The testosterone concentration did not increase significantly. The lipid peroxidation in the corpus cavernosum of the male rats administered SWP decreased significantly. In contrast, compared to the ethanol group, SWP-administered male rats showed increased GSH levels in the corpus cavernosum. The level of nitrite and NOS expression in the corpus cavernosum of SWP-administered male rats increased significantly. These results indicated that SWP effectively restored ethanol-induced ED in male rats.

Essential Amino Acid Supplementation Decreases Liver Damage Induced by Chronic Ethanol Consumption in Rats

The liver sustains the greatest damage from ethanol (EtOH) abuse. EtOH and its metabolites impair hepatocyte metabolism, causing intracellular accumulation of proteins and lipids and increasing radical oxygen species production. These processes are toxic to the mitochondrial respiratory chain and to mitochondrial DNA. We have recently shown that supplementating the diet of rodents with an essential amino acid-enriched mixture (EAAem) significantly increases mitochondrial mass and number in cardiac and skeletal muscles and improves mitochondrial function in aged animals. Thus, in this study we sought to test whether EAAem supplementation could reduce EtOH-induced liver damage. Groups of adult male Wistar rats were fed a standard diet and water ad libitum (the control group), drinking water with 20 percent EtOH (the EtOH group), or drinking water with 20 percent EtOH and EAAem supplementation (1.5 g/kg/day) (the EtOH+EAAem group) for 2 months. The blood EtOH concentration was measured, and markers for fat (Oil-Red-O), mitochondria (Grp75, Cyt-c-ox), endoplasmic reticulum (Grp78), and inflammation (Heme Oxigenase 1, iNOS, and peroxisomes) were analyzed in the liver of animals in the various experimental groups. EAAem supplementation in EtOH-drinking rats ameliorated EtOH-induced changes in liver structure by limiting steatosis, recruiting more mitochondria and peroxisomes mainly to perivenous hepatocytes, stimulating or restoring antioxidant markers, limiting the expression of inflammatory processes, and reducing ER stress. Taken together, these results suggest that EAAem supplementation may represent a promising strategy to prevent and treat EtOH-induced liver damage.

Gender‐specific vascular effects elicited by chronic ethanol consumption in rats: a role for inducible nitric oxide synthase

Epidemiological data suggest that the risk of ethanol-associated cardiovascular disease is greater in men than in women. This study investigates the mechanisms underlying gender-specific vascular effects elicited by chronic ethanol consumption in rats. Vascular reactivity experiments using standard muscle bath procedures were performed on isolated thoracic aortae from rats. mRNA and protein for inducible NO synthase (iNOS) and for endothelial NOS (eNOS) was assessed by RT-PCR or western blotting, respectively. In male rats, chronic ethanol consumption enhanced phenylephrine-induced contraction in both endothelium-intact and denuded aortic rings. However, in female rats, chronic ethanol consumption enhanced phenylephrine-induced contraction only in endothelium denuded aortic rings. After pre-incubation of endothelium-intact rings with L-NAME, both male and female ethanol-treated rats showed larger phenylephrine-induced contractions in aortic rings, compared to the control group. Acetylcholine-induced relaxation was not affected by ethanol consumption. The effects of ethanol on responses to phenylephrine were similar in ovariectomized (OVX) and intact (non-OVX) female rats. In the presence of aminoguanidine, but not 7-nitroindazole, the contractions to phenylephrine in rings from ethanol-treated female rats were greater than that found in control tissues in the presence of the inhibitors. mRNA levels for eNOS and iNOS were not altered by ethanol consumption. Ethanol intake reduced eNOS protein levels and increased iNOS protein levels in aorta from female rats. Gender differences in the vascular effects elicited by chronic ethanol consumption were not related to ovarian hormones but seemed to involve the upregulation of iNOS.

Chronic ethanol consumption in rats produces residual increases in anxiety 4 months after withdrawal

The present study investigated the long-term effects of ethanol consumption in rats. Subjects were maintained on either an ethanol (alcohol) (2.7–6.7%, v/v) or an isocaloric liquid control diet for 26 consecutive days ( M = 13.7 g/kg/day). Testing for working memory was conducted in a Morris water maze (2 trials/day for 8 days) and commenced after either a short (19 days) or long (120 days) abstinence period. This was followed by assessment of 72 h retention of passive avoidance. Animals were killed either 41 (short abstinence) or 152 days (long abstinence) post-ethanol and their brains stained with cresyl violet. Assessments of dorsal-ventral and medial-lateral cortical vertices were measured in sections derived from eight coronal planes extending +4.20 to −4.16 mm from Bregma. Results indicated that subjects in the ethanol/long abstinence group exhibited increased state anxiety due to their propensity to be thigmotaxtic (i.e., wall-hugging) in the water maze. Unfortunately, such a swim pattern precluded assessment of working memory in our subjects. No evidence of ethanol-induced memory decrements were observed on retention of passive avoidance. There was some evidence that animals in the ethanol/long abstinent group suffered cortical thinning and slight compression of the CA1 layer within the hippocampus, although age might have contributed to the former effect. It was concluded that chronic ethanol consumption increases anxiety even after an extended period of withdrawal and may conspire with age to affect cortical integrity.

Residual behavioral and neuroanatomical effects of short-term chronic ethanol consumption in rats

The residual effects of short-term chronic ethanol consumption were investigated in rats maintained on an ethanol liquid diet for 26 consecutive days (mean intake=16.1 g/kg/day). Animals were assessed for spontaneous motor activity (12 days post-ethanol), spatial working memory (17 days post-ethanol), spatial reference memory (184 days post-ethanol), and retention of passive avoidance (201 days post-ethanol). Measurements of brain weights and cortical thickness vertices within the dorsomedial and ventrolateral cortex of eight coronal planes were determined 260 days post-ethanol. Two-dimensional cell profile densities within six coronal planes and within CA1 region of the hippocampus were also obtained, along with the total volumetric measurement of the hippocampus proper. Results indicated between group differences when subjects were assessed on working memory with ethanol-treated animals exhibiting longer escape latencies in a Morris water maze, an effect partially attributed to the perseverance of ethanol-treated animals in exhibiting thigmotaxicity. No other ethanol-related behavioral impairment was noted. Neuroanatomically, ethanol-treated rats had thinner cortical mantles (6.3% and 6.6% reductions) within the frontoparietal cortex and had lower two-dimensional cell profile densities within the most caudal cortical region studied. Interestingly, control animals with thicker cortical mantles tended to perform better on the working memory task, whereas the opposite was true for ethanol-treated subjects. These data led to the conclusion that chronic ethanol consumption of a relatively short duration produces working memory impairments, albeit mild, that are partially related to an inability to abandon ineffectual behavioral strategies, and also produces neuroanatomical alterations within the cortex.

The effects of chronic ethanol consumption and ethanol withdrawal on serum cholinesterase activity in rats.

The effect of chronic ethanol consumption and ethanol withdrawal on serum cholinesterase (ChE) activity was investigated in female Wistar rats. Ethanol was administered by a modified liquid diet with 4.8% (v/v) ethanol for 3 days followed by 25 days on a liquid diet in which the ethanol concentration was increased to 7.2%. Control rats were pair-fed with an isocaloric liquid diet not containing ethanol. The blood ethanol concentration and serum ChE activity were measured at the end of the 4.8% ethanol consumption period; after 7, 14 and 35 days of ethanol (7.2%) consumption, and at 24 and 72 h after ethanol withdrawal following ethanol consumption of 35 days. Daily ethanol consumption of the rats ranged from 11.5 to 14.9 g/kg. Serum ChE activity was found significantly increased from the 3rd day of ethanol (4.8%) consumption. Serum ChE activities of the rats receiving 7.2% ethanol also increased significantly compared with rats ingesting 4.8% ethanol. Blood ethanol levels were measured as 121 and 0.88 mg/dl on the 35th day of ethanol (7.2%) consumption (just before ethanol withdrawal) and after 24 h of ethanol withdrawal, respectively. Increased serum ChE activity (1968 U/l) was still observed (1942 U/l) after 24 h of ethanol withdrawal. ChE activity returned to control levels (501 U/l) after 72 h of ethanol withdrawal. Audiogenic seizures indicating development of physical dependence on ethanol were also observed after 8 h of ethanol withdrawal in another individual group of ethanol-fed rats. Our results show that serum ChE activity is increased by chronic ethanol consumption in rats and that this increase is affected by ethanol concentration and duration of ethanol ingestion.

Sex differences in L-type calcium current after chronic ethanol consumption in rats

Chronic ethanol consumption elicits a progressive cardiac contractile dysfunction, and studies in rats suggest that this alcoholic heart muscle disease is more pronounced in males than females. Cellular changes associated with the ethanol-induced cardiotoxicity remain largely undefined; however, it is possible that L-type Ca 2+ channel current ( I Ca,L) is affected. Using whole-cell patch-clamp techniques, this study examined I Ca,L in adult ventricular myocytes isolated from male and female P-rats that had consumed drinking water (controls) or a 25% ethanol/water mixture for 14 months. The peak amplitude and maximum conductance of I Ca,L were 32 and 26% greater, respectively, in cardiomyocytes isolated from ethanol-consuming compared to control male rats. In contrast, no differences in the amplitude or conductance of I Ca,L were observed when comparing myocytes isolated from control and ethanol-consuming females. Ethanol treatment had no significant effects on the kinetics I Ca,L inactivation or on steady-state activation and inactivation in either gender. In conclusion, male but not female cardiomyocytes respond to chronic ethanol consumption with an increased I Ca,L that may represent a compensatory response to the depressed contractility.

Cytogenetic study of chronic ethanol consumption in rats.

Ethanol was supplied in the drinking water of Wistar rats at a concentration of 20% v/v for up to 30 days. The animals treated with ethanol demonstrated a nonsignificant increase in chromosomal aberration frequency when compared with control animals. The mitotic index values obtained indicated no significant differences between ethanol treatment and control groups. The final weights of control rats were significantly greater than those of the ethanol-treated group. Chronic administration of ethanol showed no clastogenic or cytotoxic effect. After chronic ethanol consumption, the cytochromes P450 activity increases, thus possibly preventing the ethanol that has entered the circulation from reaching excessive levels, leading to metabolic adaptation and/or tolerance.

Chronic ethanol consumption leads to destabilization of rat liver β-galactoside α2,6-sialyltransferase mRNA

Chronic ethanol consumption in rats is accompanied by decreased levels of Galβ1,4GlcNAc α2,6-sialyltransferase (2,6-ST) activity in the liver. Our previous studies have shown that there is a concomitant decrease in the levels of 2,6-ST mRNA. In this study, the alteration in the regulation of 2,6-ST expression by chronic ethanol consumption was assessed by Northern hybridization, nuclear run-on experiments, and 2,6-ST mRNA stability studies. 2,6-ST downregulation was found at 4 weeks of feeding an ethanol diet (36% of calories from ethanol) and remained up to 8 weeks. The decrease in 2,6-ST mRNA levels was found to be dose-dependent, with lower dose of ethanol (12% and 24% of total dietary calories from ethanol) being ineffective and the effects being manifested only when 36% of the dietary calories were from ethanol. The effects of chronic ethanol feeding could be completely reversed within 1 week after ethanol consumption was stopped, when 2,6-ST mRNA levels were restored to normal. The downregulation was not sensitive to actinomycin D, indicating that the regulation was not affected at the transcriptional level but at the posttranscriptional level. This was confirmed by nuclear run-on experiments showing that the rate of 2,6-ST mRNA transcription was unaffected by ethanol. Finally, mRNA stability experiments showed that the half-life of 2,6-ST mRNA was reduced 50% in ethanol-fed rat livers compared with control rat livers. Taken together, the results show that 2,6-ST mRNA is regulated at the posttranscriptional level and chronic ethanol intake downregulates 2,6-ST expression by destabilizing its mRNA.

Ursodeoxycholate protects against ethanol-induced liver mitochondrial injury

The purpose of this work was to examine whether ursodeoxycholate (UDC), a hydrophilic bile salt, could reduce mitochondrial liver injury from chronic ethanol consumption in rats. Animals were pair-fed liquid diets containing 36% of calories as ethanol or isocaloric carbohydrates. They were randomly assigned into 4 groups of 7 rats each and received a specific treatment for 5 weeks: control diet, ethanol diet, control diet + UDC, and ethanol diet + UDC. Respiratory rates of isolated liver mitochondria were measured using a Clark oxygen electrode with sodium succinate as substrate. Mitochondria from rats chronically fed ethanol demonstrated an impaired ability to produce energy. At the fatty liver stage, the ADP-stimulated respiration (V3) was depressed by 33%, the respiratory control ratio (RC) by 25% and the P O ratio by 15%. In ethanol-fed rats supplemented with UDC, both the rate and efficiency of ATP synthesis via the oxidative phosphorylation were improved: V3 was increased by 35%, P O by 8%. All the respiratory parameters were similar in control group and control + UDC group. On the other hand, the number and size of mitochondria were assessed by electron microscopy and computer-assisted quantitative analysis. The number of mitochondria from ethanol-treated rats was decreased by 29%, and they were enlarged by 74%. Both parameters were normalized to control values by UDC treatment. These studies demontrate that UDC has a protective effect against ethanol-induced mitochondrial injury by improving ATP synthesis and preserving liver mitochondrial morphology. These UDC positive effects may contribute to the observed decrease in fat accumulation and may delay the progression of alcoholic injury to more advanced stages.

Taurine: protective properties against ethanol-induced hepatic steatosis and lipid peroxidation during chronic ethanol consumption in rats.

Alcohol was administered chronically to female Sprague Dawley rats in a nutritionally adequate totally liquid diet for 28 days. This resulted in hepatic steatosis and lipid peroxidation. Taurine, when co-administered with alcohol, reduced the hepatic steatosis and completely prevented lipid peroxidation. The protective properties of taurine in preventing fatty liver were also demonstrated histologically. Although alcohol was found not to affect the urinary excretion of taurine (a non-invasive marker of liver damage), levels of serum and liver taurine were markedly raised in animals receiving alcohol + taurine compared to animals given taurine alone. The ethanol-inducible form of cytochrome P-450 (CYP2E1) was significantly induced by alcohol; the activity was significantly lower than controls and barely detectable in animals fed the liquid alcohol diet containing taurine. In addition, alcohol significantly increased homocysteine excretion into urine throughout the 28 day period of ethanol administration; however, taurine did not prevent this increase. There was evidence of slight cholestasis in animals treated with alcohol and alcohol + taurine, as indicated by raised serum bile acids and alkaline phosphatase (ALP). The protective effects of taurine were attributed to the potential of bile acids, especially taurine conjugated bile acids (taurocholic acid) to inhibit the activity of some microsomal enzymes (CYP2E1). These in vivo findings demonstrate for the first time that hepatic steatosis and lipid peroxidation, occurring as a result of chronic alcohol consumption, can be ameliorated by administration of taurine to rats.

Serum carbohydrate-deficient transferrin: Mechanism of increase after chronic alcohol intake

Carbohydrate-deficient transferrin (CDT) is now considered to be the most sensitive and specific biological marker of alcohol abuse. However, the mechanism by which chronic alcohol consumption causes an elevation of CDT levels in serum is still not understood. Therefore, we fed eight pairs of male rats a nutritionally adequate liquid diet containing either alcohol (36% of energy) or isocaloric dextrose (control) for 4 weeks, after which blood and liver samples were obtained. Serum CDT content in alcohol-treated rats increased by 45% ( P < .05) as assessed with an isoelectric focusing/Western blot method (IEF/WB) thereby mimicking the clinical condition. In particulate fractions (plasma membranes) prepared from the liver samples, the activity of sialidase was increased 1.62-fold ( P < .05) in ethanol-fed animals compared with their corresponding controls. In contrast, in rats fed ethanol, the activities of sialyltransferase (ST), galactosyltransferase (GT), and N-acetylglucosamine transferase ( N-AGT), which are glycosyltransferases involved in transferrin carbohydrate side chain synthesis, were diminished by 24% and 40% ( P < .05), 23% and 51% ( P < .05, .001), and 20% and 26% ( P < .05) in total liver homogenates and Golgi fraction (GF) 1, respectively, when expressed as units/100 g body weight. These enzymes were also significantly less active in hepatic GFs 2 and 3. The depression of the transferase activities in ethanol-fed rats appeared to be due, at least in part, to enzyme inactivation by acetaldehyde, whereas ethanol itself was without effect. Similar results were obtained in humans: five alcohol abusers were found to exhibit a 23% decrease in hepatic sialyltransferase and a 41% increase in sialidase activities, respectively, when compared with three nondrinking subjects. In conclusion, the increased activity of sialidase in liver particulate fractions, combined with the decrease in transferrin glycosyltransferases in GFs, mediated by ethanol (or acetaldehyde derived from ethanol) most likely accounts for the enhanced serum CDT in response to chronic ethanol consumption in rats as well as in humans.

Alterations in hepatic δ-aminolevulinic acid synthetase and heme oxygenase activities after chronic ethanol consumption in rats

In the present study, the effect of chronic ethanol consumption in rats on the hepatic heme metabolism was investigated. Male Wistar rats were fed a nutritionally adequate liquid diet containing ethanol as 36% of the total calories for 5 weeks. After an overnight fast, the livers were excised and centrifuged to obtain mitochondrial and microsomal fractions. Chronic ethanol feeding of rats resulted in about 19% hepatomegaly as represented by the increased liver/body weight ratio. There was no difference in the mitochondrial protein content between the ethanol-treated and control rats, but the microsomal protein content was significantly increased in the ethanol-treated rats. Hepatic microsomal content of cytochrome P-450 (P-450) was markedly enhanced by chronic ethanol ingestion. Microsomal contents of cytochrome b5 (b5) and total heme were also increased to a lesser extent. After chronic ethanol abuse, the hepatic activity of delta-aminolevulinic acid (ALA) synthetase, which is a rate-limiting enzyme for heme production, was significantly increased and that of the heme oxygenase was slightly increased. These data indicate that ALA synthetase activity is induced by the negative feedback mechanism in order to compensate the depletion of heme caused by the utilization of heme for P-450. It is also speculated that, in response to excessive production of heme as described above, heme oxygenase activity is secondarily induced to regulate the amount of heme.

Central histaminergic stimulation of corticosterone and hyperlipemic responses after chronic ethanol consumption in rats.

The consumption of ethanol in a 10% solution for 3 weeks produced a negligible increase in corticosterone secretion in the rat but raised the levels of free fatty acid (FFA) in the serum. Mepyramine insignificantly antagonized and cimetidine intensified the corticosterone response. Histamine and the H1- and H2-receptor agonists, 2-pyridylethylamine (PEA) and dimaprit significantly raised the serum corticosterone levels in chronically alcoholized rats. Mepyramine antagonized and cimetidine increased the ethanol-induced hyperlipemia. Histamine, PEA and dimaprit considerably increased the serum FFA levels in alcoholized rats. After withdrawal of ethanol, histamine and dimaprit induced a marked hyperlipemic effect, whereas PEA did not increase the serum FFA concentration. These results indicate that in chronically alcoholized rats the central histaminergic system interacts with ethanol in regulation of the serum FFA level. After the ethanol withdrawal central H1-receptors do not respond to H1-agonist stimulation.

Alcohol and cancer.

Alcohol and cancer.

The effect of chronic ethanol consumption on salivary gland morphology and function in the rat.

Chronic ethanol consumption in rats resulted in a striking fat accumulation in the acinar cells of the parotid gland demonstrated by light microscopy. In addition, a significant decrease in parotid wet weight (p greater than 0.02) and in protein content of the gland (p greater than 0.02) was observed following alcohol feeding. Wet weight, protein content, and morphology of the submaxillar gland were not affected by ethanol feeding. Alcohol metabolism, similar to that found in the pancreas, via a cytosolic alcohol dehydrogenase could be demonstrated in both the parotid and the submaxillar gland. However, the activity of this enzyme was not affected by chronic ethanol ingestion. Subsequently, chronic ethanol consumption significantly decreased salivary flow rate stimulated by pilocarpine hydrochloride (p greater than 0.02), salivary alpha-amylase activity (p greater than 0.02), and salivary sodium concentration (p greater than 0.01), whereas potassium concentration of the saliva was increased (p greater than 0.05). In contrast salivary total protein concentration was not affected by alcohol ingestion. The changes of salivary electrolyte composition observed after chronic ethanol feeding could be due to an altered aldosterone metabolism or to a change in aldosterone receptors of the parotid gland caused by ethanol administration. The reduced salivary flow could play a role in the pathogenesis of oropharyngeal cancer in the alcoholic.

Effect of acute and chronic ethanol consumption on hepatic tissue oxygen tension in rats

In vivo hepatic tissue oxygenation was investigated in chronically ethanol-treated rats using micro oxygen electrode and reflectance spectrophotometry. Effect of acute ethanol administration was also studied. Hepatic oxygen tension of rats treated with ethanol chronically (daily ethanol intake, 9∼12 g/kg for 9 months) was very low as compared with that of normal rats, the decrease being comparable to that of rats treated with carbon tetrachloride. The hepatic oxygen tension in normal controls shortly after ethanol ingestion increased from basal level (median, 23 mmHg) to 40∼70 mmHg, while in chronically ethanol-treated rats, the hepatic oxygen tension decreased transiently, followed by a gradual increase, but it still remained low. In CCl 4-treated rats, the hepatic oxygen tension decreased further after the ethanol ingestion. It is concluded that chronic ethanol consumption in rats resulted in hepatic hypoxia with decreased liver blood flow and volume. Also acute ethanol administration does not induce hepatic hypoxia in normal rats, while in rats with injured liver it induces hypoxia.

Female reproduction during chronic ethanol consumption in rats

This study was undertaken to ascertain ovarian function under the conditions of ethanol withdrawal and continued ethanol treatment to distinguish between a temporary delay in ovarian activity and a permanent suppression of ovarian function. Immature rats were fed the following diets for 16 weeks: a liquid diet containing 5% ethanol, a liquid diet without ethanol (pair-fed controls), a liquid diet with 5% ethanol for eight weeks followed by laboratory chow and water for eight weeks, or chow and water ad lib. Vaginal patency was significantly delayed in both groups of ethanol-treated rats compared to controls. The duration of an estrous cycle for the rats in the ad lib group was 5.0±0.3 days, while a “regular” estrous cycle was four to six days in duration. The rats which received ethanol for 16 weeks exhibited more irregular estrous cycles (both<4 and >6 days) than the rats with other treatments and the cycles were significantly longer. After 16 weeks of treatment, the rats were mated; ethanol was not given during pregnancy. The average number of pups per litter and body weight of the offspring were similar for all groups. These data show that although ethanol alters normal cyclic activity, it does not totally suppress ovarian function since alcohol-treated rats were capable of mating and delivering viable offspring.