Oral Administration Of Ethanol Research Articles

Caffeic acid alleviates the increased lipid levels of serum and tissues in alcohol‐induced rats

Ethanol is one of the most widely used and abused drugs that increases lipid levels in human and experimental animals. The objective of this study was to determine the effect of caffeic acid (CA) on alcohol-induced alterations of lipid levels in serum, liver and kindey of Wistar rats. The alcohol toxicity was induced by oral administration of ethanol (7.9 g/kg/bw) for 45 days through intragastric intubation. The elevation in the levels of lipids upon alcohol administration was accompanied by a significant increase in the levels of cholesterol, phospholipids (PL), free fatty acids (FFA) and triglycerides (TG) in serum, liver and kidney. Oral administration of CA (12 mg/kg/bw) to alcohol fed rats significantly decreased the serum and tissue lipid levels to near those of the control rats. In conclusion, our study suggests that oral administration of CA to alcohol fed rats markedly reduced the accumulation of cholesterol, TG, FFA and PL in circulation, liver and kidney.

Antiulcerogenic activity of bark extract of Tabebuia avellanedae, Lorentz ex Griseb

Tabebuia avellanedae is commonly used for the treatment of peptic ulcers. We carried out this study with the ethanolic extract of bark from Tabebuia avellanedae (EET) (30–1000 mg/kg) to determine its gastroprotective activity and to clarify the pathways involved in this effect. Acute gastric ulceration in rats was produced by oral administration of ethanol and ibuprofen. After ethanol administration, the gastric wall mucus was examined. Chronic gastric ulceration was produced by injection of acetic acid in rat gastric subserosa. Anti-secretory studies were undertaken using Shay rat pylorus ligature technique and measurement of enzymatic activity of H +, K +-ATPase in vitro. Administration of EET p.o. or i.p. significantly inhibited gastric mucosa damage induced by ethanol and ibuprofen. The anti-ulcer effect was further confirmed by enhanced gastric mucus production. In pylorus ligature rats, EET significantly reduced the basal gastric acid secretion and total acidity; moreover, it inhibited the increase in total acidity induced by histamine. In addition, EET reduced the activity of H +, K +, ATPase. The results obtained in the present pharmacological assay indicate that this plant has a protective action against gastric lesions, involving the maintenance of protective factors, such as mucus and prostaglandin, besides the reduction of gastric total acidity.

Gastroprotective Effects of Melastoma malabathricum Aqueous Leaf Extract against Ethanol-Induced Gastric Ulcer Iin Rats

The gastro-protective effects of the aqueous leaf extract of Melastoma malabathricum was investigated against ethanol-induced gastric mucosal injuries in rats. There were four groups of adult sprague dawley rats, consisting of six rats per group. Macroscopically, oral administration of absolute ethanol to rats that had been pre-treated with only distilled water significantly produced extensive lesions of the gastric mucosa. Oral pre-treatment with either 250 mg kg−1 of M. malabathricum extract, 500 mg kg−1 of M. malabathricum extract, or 20 mg kg−1 of omeprazole 60 minutes before administration of absolute ethanol significantly reduced the formation of gastric mucosal injuries. The observed protection was significant and dose dependent in inhibiting ethanol-induced gastric ulcers. Microscopically, rats that had been pre-treated with only distilled water showed marked damage of the gastric mucosa, induced submucosal edema and leucocytes infiltration. However, animals that had been pre-treated with aqueous leaf extracts or omeprazole showed marked reduction of gastric mucosal damage, reduction of oedema and less leucocyte infiltration of submucosal layer. The results indicated that 500 mg kg-1 aqueous leaf extract of M. malabathricum provided the best protection to the gastric mucosa in rats against ethanol-induced gastric ulcers.

Altered water–maze search behavior in adult guinea pigs following chronic prenatal ethanol exposure: Lack of mitigation by postnatal fluoxetine treatment

Ingestion of ethanol during pregnancy can result in teratogenic effects in humans, including significant and long-lasting neurobehavioral deficits. Similar results are seen in guinea pigs with chronic prenatal ethanol exposure (CPEE) via maternal ethanol administration, which produces deficits in Morris water–maze performance and impaired hippocampal functioning (e.g., decreased long-term potentiation, LTP). In this study, we tested whether postnatal treatment with fluoxetine, a selective serotonin reuptake inhibitor, decreases some of the neurobehavioral impairments produced by CPEE. Timed, pregnant guinea pigs received oral administration of ethanol (4g/kg maternal body weight) or isocaloric sucrose pair feeding (control) for 5 days/week throughout gestation. Offspring of the CPEE and control groups were randomly assigned to receive either fluoxetine (10mg/kg body weight/day) or saline intraperitoneally from postnatal day 10 to 48. Subsequent behavioral tests in the Morris water–maze revealed a significant increase in thigmotaxic swimming in CPEE offspring without apparent signs of impairment in spatial mapping of the hidden escape platform. Measures of hippocampal short- and long-term plasticity (paired-pulse facilitation, frequency facilitation, and LTP) were unaffected by CPEE, consistent with the behavioral data indicating normal hippocampal functioning. Postnatal fluoxetine administration resulted in a significant loss of body weight, but did not affect the increased thigmotaxic swimming following CPEE. These results indicate that changes in search strategies in the water–maze might be a highly sensitive index of CPEE-induced neurobehavioral toxicity that can occur in the absence of significant hippocampal dysfunction. Further, these data demonstrate that fluoxetine, at the selected treatment regime, does not mitigate the thigmotaxic swimming response to CPEE in the guinea pig.

Two kinds of behavioral evaluation of intoxication by oral administration of ethanol in mice

Evaluation of ethanol intoxication in humans has difficulties in individual differences and ethical considerations. Intraperitoneal injection of ethanol has been used in evaluation of ethanol intoxication in nonhuman animals. We have developed two kinds of behavioral evaluations of intoxication by oral administration of ethanol in mice. Oral administration of ethanol (1.6∼4.0g/kg as a single dose, 0.8∼1.6g/kg dosed twice) increased both the number of open-arm entries and the time spent in the open arm of the elevated plus-maze test, demonstrating an anxiolytic-like effect of ethanol. Oral administration of ethanol (1.6 or 4.0g/kg single dose, 1.2 or 2.4g/kg dosed twice) significantly decreased locomotor activity under fasting conditions. Under semi-fasting conditions, oral administration of ethanol (1.6g/kg single dose) transiently enhanced locomotor activity 1 h after administration but decreased subsequently for 48 h. Elevated plus maze and locomotor activity are useful for analyzing mild and mild-to-severe intoxicaton, respectively, caused by oral administration of ethanol on the condition used in this study.

アルコールと脳内微量元素

When men drink excessive amounts of alcohol over a prolonged period, they may develop neurological diseases, such as peripheral neuropathy, Wernicke encephalopathy, and alcohol-induced cerebellar degeneration. Trace elements in the brain can lead to the increased expression of receptors, enzymes for the synthesis and metabolism of the neurotransmitter, and proteins that modulate function, ets. It is possible that various neurological symptoms occur when trace elements in the brain are affected by excessive consumption of alcohol, even though the trace elements in the brain are maintained at a constant level. Drinking excessive levels of alcohol increases the level of zinc in the brain, while lower levels of zinc in blood are seen in men with signs of chronic excessive alcohol consumption, such as with alcoholic cirrhosis. It is speculated that increased free radicals by acute alcoholic intake, cause zinc to be increased in the brain in response to this phenomenon. Copper is closely related to neurological diseases, such as Wilson′s disease or Menkes disease, but there have been no reports regarding encephalopathy induced by changes in copper and its metabolites in the brain due to drinking. About 80% of manganese in the brain exists within the astrocytes, and is involved in glutamine metabolism. However, there have not been many reports concerning the relation between alcohol and manganese. Low levels of manganese in the blood are observed in chronic alcoholics and these patients exhibit delirium tremens, tetany, convulsions, athetosis and involuntary movement. The level of iron in the blood increases with chronic excessive alcohol drinking, but there have been no reports indicating that iron levels in the brain are modified by alcohol intake. Metal-lothionein (MT) contributes significantly to zinc and copper metabolism and functions as a protective protein, but MT in the brain is increased when the MT-I overexpressing transgenic mouse (MT-I*) is administered 4 g/kg of ethanol by a gastric tube. Acute ethanol administration can generate oxygen free radicals and cause oxidative stress in the brain. The mechanism of induction of MT in the brain after oral ethanol administration may be associated with oxidative stress caused by ethanol or its metabolites, and can be considered a protective mechanism against ethanol toxicity.

Gastro-Resistant Microparticles Containing Sodium Pantoprazole: Stability Studies and In Vivo Anti-Ulcer Activity

The aim of the present work was to verify the in vivo capacity of pantoprazole-loaded microparticles to protect the gastric mucosa against ulcer formation and to evaluate their stability under accelerated conditions. Pantoprazole- loaded microparticles were prepared by spray-drying in pilot scale, using Eudragit ® S100 as polymer. Transparent glass vials containing drug-loaded microparticles were stored for 6 months at 40°C and 75% RH. Photostability was tested un- der UVA light. Ulcers were induced by the oral administration of absolute ethanol to rats. Sodium bicarbonate solution, pantoprazole solution and drug-loaded microparticles were tested. Regarding the drug content during the accelerate stabil- ity study, samples showed complete encapsulation efficiency and were considered stable. The microencapsulation of pan- toprazole reduced its photodegradation. The in vivo evaluation showed that the microparticles presented ulcer index lower than the solutions. Enteric microparticles had acceptable stability under accelerated conditions and were efficient in pro- tecting the stomach against ulceration caused by ethanol.

Effects of Marjoram Volatile Oil and Grape Seed Extract on Ethanol Toxicity in Male Rats

Natural dietary antioxidants are extensively studied for their ability to protect cells from miscellaneous damages. Marjoram volatile oil (Origanum majorana L., Lamiaceae) and grape seed extract (Vitis vinifera L., Vitaceae) are potent antioxidants. Effects of administration of marjoram volatile oil or grape seed extract on oral administration of ethanol, simultaneously, daily for 10 weeks were studied through determining epididymal spermatozoal analysis, serum testosterone level, weight and histopathological examination of testis, liver and brain. Glutathione level and lipid peroxidation content as malondialdehyde in the testis, liver and brain were measured. The repeated intake of a great amount of ethanol (10 ml/kg body weight, 25% v/v) was followed by fertility disturbances with low sperm count, impaired sperm motility and decrease in serum testosterone level. Moreover, ethanol toxicity induced significant alterations in the histological structures of the testis, liver and brain. The results revealed a significant increase in lipid peroxidation and decrease in the level of glutathione in the testis, liver and brain in the ethanol-treated group. However, co-administration of the extracts of protective plants resulted in minimizing the hazard effects of ethanol toxicity on male fertility, liver and brain tissues. It may be concluded that marjoram volatile oil and grape seed extract are useful herbal remedies, especially for controlling oxidative damages.

Protective Effect of Collagen Derivates on the Ulcerative Lesions Caused by Oral Administration of Ethanol

The protective effect of beef and pig collagen hydrolysates and their fractions were tested as anti-ulcerogenic agents in rats (weighing 250-350 g) against ulcerative lesions caused by ethanol. Beef and pig collagen hydrolysates were fractionated by ultrafiltration into different molecular weight fractions. The protocol employed a negative and a positive control and a single dose of the experimental samples given by intragastric intubation. The beef collagen did not present a dose-response correlation in the ethanol model, whereas pig collagen showed a logarithmic dose-response relationship. Beef collagen hydrolysate decreased the ulcerative lesion index of 55% versus a 61% decrease for pig collagen hydrolysate at the same dosage (750 mg/kg of body weight). No significant differences were found (P > .05) between the hydrolysates and their fractions.

Different patterns in the induction of metallothionein mRNA synthesis among isoforms after acute ethanol administration

The induction of metallothionein (MT) isoform synthesis was investigated in mouse cerebral cortex 18 h after oral ethanol administration. The expression of MT-I isoform mRNA increased in a dose-dependent manner after ethanol loading at doses between 2 g/kg (ethanol/body weight) and 8 g/kg. Lipid peroxide formation, measured as the amount of malondialdehyde- reactive substances, remained at the control level after all of the administered ethanol doses. The expression of MT-III isoform mRNA remained at the control level up until an ethanol loading dose of 4 g/kg and then finally increased to a significant level at a dose of 8 g/kg, which is almost the LD50 for oral ethanol in mice. The different patterns of MT synthesis induction among MT isoforms suggests that the MT-I isoform, which is ubiquitous in mammalian tissues, plays a significant role as an antioxidant. On the other hand, the MT-III isoform, which has a limited tissue distribution, especially in the central nervous system, seems to be implicated in tissue repair and/or protection against critical tissue injury.

Chronic Prenatal Ethanol Exposure Increases Glucocorticoid‐Induced Glutamate Release in the Hippocampus of the Near‐Term Foetal Guinea Pig

Exposure to high cortisol concentration can injure the developing brain, possibly via an excitotoxic mechanism involving glutamate (Glu). The present study tested the hypothesis that chronic prenatal ethanol exposure (CPEE) activates the foetal hypothalamic-pituitary-adrenal axis to produce high cortisol exposure in the foetal compartment and alters sensitivity to glucocorticoid-induced Glu release in the foetal hippocampus. Pregnant guinea pigs received daily oral administration of ethanol (4 g/kg maternal body weight/day) or isocaloric-sucrose/pair-feeding from gestational day (GD) 2 until GD 63 (term, approximately GD 68) at which time they were euthanised, 1 h after their final treatment. Adrenocorticotrophic hormone (ACTH) and cortisol concentrations were determined in foetal plasma. Basal and electrically stimulated Glu and gamma-aminobutyric acid (GABA) efflux in the presence or absence of dexamethasone (DEX), a selective glucocorticoid-receptor agonist, were determined ex vivo in foetal hippocampal slices. Glucocorticoid receptor (GR), mineralocorticoid receptor (MR) and N-methyl-D-aspartate (NMDA) receptor NR1 subunit mRNA expression were determined in situ in the hippocampus and dentate gyrus. In the near-term foetus, CPEE increased foetal plasma ACTH and cortisol concentrations. Electrically stimulated glutamate, but not GABA, release was increased in CPEE foetal hippocampal slices. Low DEX concentration (0.3 microM) decreased stimulated glutamate, but not GABA, release in both CPEE and control foetal hippocampal slices. High DEX concentration (3.0 microM) increased basal release of Glu, but not GABA, in CPEE foetal hippocampal slices. GR, but not MR, mRNA expression was elevated in the hippocampus and dentate gyrus, whereas NR1 mRNA expression was increased in the CA1 and CA3 fields of the foetal hippocampus. These data demonstrate that CPEE increases high glucocorticoid concentration-induced Glu release in the foetal hippocampus, presumably as a consequence of increased GR expression. These effects of CPEE, coupled with increased glutamate release and increased NMDA receptor expression, may predispose the near-term foetal hippocampus to GR and Glu-NMDA receptor-mediated neurodevelopmental toxicity.

Effect of Cardiospermum halicacabum on ethanol-induced gastric ulcers in rats

Ethanol extract of Cardiospermum halicacabum Linn. (Sapindaceae), in a concentration dependant manner (200–600 mg/kg) inhibited gastric ulcers induced by oral administration of absolute ethanol. Further, the extract administration to rats resulted in an increase in levels of gastric glutathione and a decrease in alkaline phosphatase activity. The extract also exhibited potent in vitro hydroxyl radical scavenging and inhibition of lipid peroxidation activities. The extract was found to be devoid of any conspicuous acute and short-term toxicity in rats.

Roles of nitric oxide in protective effect of berberine in ethanol-induced gastric ulcer mice1

To investigate the protective effects of berberine on ethanol-induced gastric ulcer in mice. Gastric ulcers were induced by oral ingestion of ethanol. Nitric oxide (NO) content was measured, and mRNA expression of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). The ulcer index (UI) at 1 h, 2 h, 3 h and 6 h after oral administration of ethanol was 23.8+/-1.4, 23.3+/-2.2, 22.3+/-1.2 and 20.8+/-1.1, respectively. The UI in the berberine-treated groups (5 mg/kg and 50 mg/kg) was less than the control group. The content of NO in the control group was 73.3+/-7.3 microL/L, 94.0+/-9.2 microL/L, 109.6+/-6.4 microL/L and 138.2+/-10.2 microL/L in gastric juice and 5.8+/-1.1 micromol/g protein, 8.3+/-1.1 micromol/g protein, 9.8+/-1.1 micromol/g protein and 11.9+/-1.2 micromol/g protein in gastric tissue at 1 h, 2 h, 3 h and 6 h, respectively, after the oral administration of ethanol. The content of NO in the berberine-treated groups (5 mg/kg and 50 mg/kg) was higher than the control group at 1 h after the oral administration of ethanol (P<0.05), and was lower at 6 h (P<0.05). Analysis by RT-PCR showed that expression of eNOS was inhibited but iNOS expression was enhanced by ethanol. However, the expression of eNOS could be enhanced and iNOS expression could be inhibited by berberine (P<0.01). Berberine could significantly protect gastric mucosa from damage by ethanol. This effect may be related to the increased expression of eNOS mRNA and inhibited expression of iNOS mRNA.

Alcohol- and Light-induced Electro-oculographic Responses in Age-related Macular Degeneration &amp; Central Serous Chorioretinopathy

The non-photic electro-oculographic (EOG) response induced by alcohol has been proposed as an indicator of retinal pigment epithelial (RPE) integrity, and reported to be abnormal in age-related macular degeneration (ARMD). To evaluate this proposal, we have measured the alcohol-EOG as well as the ISCEV-standard EOG in patients with ARMD (n=11 patients, 4 eyes with drusen, 8 eyes with 'dry' and 7 eyes with 'wet' lesions) and central serous chorioretinopathy (CSC, n=11 patients, 7 eyes with active and 6 eyes with inactive lesions), compared with 29 normal controls. We recorded the alcohol-induced EOG response after a single oral administration of ethanol at 160 mg/kg, followed by an ISCEV-standard EOG. Blood alcohol levels were monitored with a breath analyzer. We found that neither the alcohol-EOG nor the light-induced EOG response showed any difference between either ARMD or CSC patients and normal controls. Nor was there difference among eyes of different ARMD or CSC subgroups. In addition, blood alcohol concentrations near the time of the alcohol-EOG peak showed no obvious relationship with peak/baseline ratios. These data suggest that neither the alcohol- nor the light-induced EOG is a sensitive indicator of these diseases.

Memory enhancing and neuroprotective effects of selected ginsenosides

The effects of ginsenosides Rg3(R), Rg3(S) and Rg5/Rk1 (a mixture of Rg5 and Rk1, 1:1, w/w), which are components isolated from processed Panax ginseng C.A. Meyer (Araliaceae), on memory dysfunction were examined in mice using a passive avoidance test. The ginsenosides Rg3(R), Rg3(S) or Rg5/Rk1, when orally administered for 4 days, significantly ameliorated the memory impairment induced by the single oral administration of ethanol. The memory impairment induced by the intraperitoneal injection of scopolamine was also significantly recovered by ginsenosides Rg3(S) and Rg5/Rk1. Among the three ginsenosides tested in this study, Rg5/Rk1 enhanced the memory function of mice most effectively in both the ethanoland scopolamine-induced amnesia models. Moreover, the latency period of the Rg5/Rk1-treated mice was 1.2 times longer than that of the control (no amnesia) group in both models, implying that Rg5/Rk1 may also exert beneficial effects in the normal brain. We also evaluated the effects of these ginsenosides on the excitotoxic and oxidative stress-induced neuronal cell damage in primary cultured rat cortical cells. The excitotoxicity induced by glutamate or N-methyl-D-aspartate (NMDA) was dramatically inhibited by the three ginsenosides. Rg3(S) and Rg5/Rk1 exhibited a more potent inhibition of excitotoxicity than did Rg3(R). In contrast, these ginsenosides were all ineffective against the H2O2- or xanthine/xanthine oxidase-induced oxidative neuronal damage. Taken together, these results indicate that ginsenosides Rg3(S) and Rg5/Rk1 significantly reversed the memory dysfunction induced by ethanol or scopolamine, and their neuroprotective actions against excitotoxicity may be attributed to their memory enhancing effects.

Radioprotective activities of beer administration for radiation-induced acute toxicity in mice

We previously found that drinking beer reduces chromosome aberrations in blood lymphocytes that were collected and irradiated in vitro. In this study, we investigated the radioprotective activities of beer-administration for bone marrow and intestine in mice. C3H/He female mice received an oral administration of beer, ethanol or saline at a dose of 1 ml/mouse 30 min before whole body irradiation with 137Cs gamma rays or LET 50 keV/microm carbon ions. Radioprotective activities were estimated using a LD(50/30) (The dose required to kill 50% of the mice within 30 days) and a microcolony technique for intestine. The LD(50/30) for the beer-administered mice was significantly increased in comparison with saline administered mice. The LD(50/30) of gamma-ray was 7.8 Gy (p < 0.05), 7.6 Gy and 7.3 Gy for beer-, ethanol- and saline-administered group, respectively. The LD(50/30) of carbon ions was 6.6 Gy (p < 0.05), 6.2 Gy and 5.9 Gy for the beer-, ethanol- and saline-administered groups, respectively. The crypt survivals that were semi-logarithmically plotted against dose were well fitted to a linear regression line. The dose reduction factor (DRF) (D10) of beer- and ethanol-administered mice for gamma rays was 1.09 and 1.08, respectively. The DRF (D10) of beer- and ethanol-administered mice for carbon ions was 1.08 and 1.07, respectively. The radioprotection by beer-administration is due to not only OH radical-scavenge action by the ethanol contained in beer.

Spatial acquisition in the Morris water maze and hippocampal long-term potentiation in the adult guinea pig following brain growth spurt–prenatal ethanol exposure

Previous work has demonstrated that in the guinea pig, chronic prenatal ethanol exposure throughout gestation can result in deficits in spatial learning in the Morris water maze and impaired hippocampal long-term potentiation (LTP). The behavioural effects are known to be dose dependent because water maze deficits occur at a dose of 4 g ethanol/kg maternal body weight/day, but not at a dose of 3 g/kg/day, administered throughout gestation. It is possible that the gradual, progressive development of tolerance to ethanol throughout gestation limits ethanol toxicity, especially for lower doses of ethanol. The present study examined whether neurobehavioural deficits are produced by prenatal ethanol exposure at a dose of 3 g/kg/day, administered only during the brain growth spurt (BGS), a regimen designed to limit the development of ethanol tolerance. Pregnant guinea pigs [term, about gestational day (GD) 68] received oral administration of ethanol (1.5 g/kg maternal body weight/day on GD 43 and 44 and then 3 g/kg maternal body weight/day from GD 45 to 62), isocaloric-sucrose/pair-feeding, or water. Offsprings were studied between postnatal days (PD) 40 and 80. The maternal blood ethanol concentration (BEC) on GD 57 or 58, at 1 h after the daily dose, was 245±19 mg/dl ( n=7). This BGS–prenatal ethanol exposure regimen did not affect spatial learning performance in the Morris water maze over a 7-day test period or in the LTP recorded in the CA1 region of the hippocampus. Thus, even when limiting the development of ethanol tolerance seen with chronic ethanol treatment throughout gestation, ethanol exposure during the BGS does not result in deficits in the behavioural and electrophysiological measures of hippocampal integrity assessed in the present study. These data indicate that in the guinea pig, the BGS may not constitute a critical period of vulnerability for ethanol-induced deficits in spatial learning or hippocampal synaptic plasticity in young adult offspring.

Liver asialoglycoprotein receptor levels correlate with severity of alcoholic liver damage in rats.

It has been demonstrated that the oral administration of ethanol (Lieber-DeCarli liquid diet) to rats results in a decreased expression and content of the asialoglycoprotein receptor (ASGP-R) in the resultant fatty liver. In the present study, we wanted to determine whether the extent of impaired receptor content was correlated with the severity of liver pathology by using the intragastric feeding model. When ASGP-R protein and mRNA levels were measured in animals infused with ethanol or dextrose in the presence of fish oil (FO) or medium-chain triglyceride as the source of fat, more significant impairments to the ASGP-R were observed in the FO-ethanol group compared with the medium-chain triglyceride-ethanol group. Furthermore, only the FO-ethanol group showed pathological liver changes. These results demonstrate that a correlation exists between the progression of alcohol-associated liver injury, as defined by the severity of liver pathology, and an ethanol-induced decline in ASGP-R content.

Protection by hot water extract of Panax notoginseng on chronic ethanol-induced hepatotoxicity.

The purpose of this study was to investigate the antioxidant effects of a hot water extract of Panax notoginseng (PNG) against chronic ethanol-induced hepatotoxicity. Fifty mice were divided into fi ve equal groups with 10 in each group. Group 1 (control) received saline, whereas group 2 received ethanol (70%, 0.1 mL, p.o.) once daily for 4 weeks, which induced hepatotoxicity, manifested biochemically by a significant elevation of serum enzyme activities, such as SGOT and SGPT. Hepatotoxicity was further evidenced by a significant increase in the hepatic lipid peroxidation measured. Groups 3-5 were administered a hot water extract of PNG at doses of 10, 25 and 50 mg/kg 2 weeks after initiating oral administration of ethanol, for a further 2 weeks. PNG ameliorated the rise in serum sGOT and sGPT induced by chronic ethanol administration. The mice were killed after PNG administration. In a separate study, PNG inhibited the lipid peroxidation in the mouse liver homogenate induced by ethanol in a dose-dependent manner. The findings indicate that PNG is an efficient cytoprotective agent against chronic ethanol-induced hepatotoxicity, possibly through inhibition of the production of oxygen-free radicals that cause lipid peroxidation.

Chronic prenatal ethanol exposure-induced decrease of guinea pig hippocampal CA1 pyramidal cell and cerebellar Purkinje cell density.

The brain is a key target of ethanol teratogenicity, in which ethanol can produce neurodegeneration in selected areas, including the hippocampus and cerebellum. The research objective was to test the hypothesis that chronic prenatal ethanol exposure, via maternal ethanol administration, produces differential time course of decreased linear density of hippocampal CA1 pyramidal cells and cerebellar Purkinje cells. Timed pregnant guinea pigs received chronic oral administration of ethanol, isocaloric-sucrose/pair-feeding, or water throughout gestation (term, about gestational day (GD) 68), and the offspring were studied at GD 62 (near-term fetus), postnatal day (PD) 1 (neonate), PD 5, and PD 12 (early postnatal life). Ethanol treatment, compared with isocaloric-sucrose/pair-feeding and water treatments, decreased brain, hippocampal, and cerebellar weights at GD 62, PD 1, PD 5, and PD 12. Hippocampal CA1 pyramidal cell linear density and cerebellar Purkinje cell linear density were unaffected at GD 62. Ethanol treatment produced 25, 30, and 30% decreases in linear density of hippocampal CA1 pyramidal cells at PD 1, PD 5, and PD 12, respectively, and a 30% decrease in linear density of cerebellar Purkinje cells at PD 12 only. At PD 5, Purkinje cell profile linear density remained unaffected; however, ethanol treatment appeared to increase linear density of apoptotic Purkinje cell nuclei, as determined by a modified TUNEL method. The data demonstrate that chronic prenatal ethanol exposure produces apparent differential time course of decreased linear density of hippocampal CA1 pyramidal cells and cerebellar Purkinje cells in the developing guinea pig.