Antioxidant effects of the chestnut (Castanea crenata) inner shell extract in t-BHP-treated HepG2 cells,and CCl4- and high-fat diet-treated mice

The antioxidant effects of chestnut inner shell extract (CISE) were investigated in a tert-butylhydroperoxide (t-BHP)-treated HepG2 cells, and in mice that were administered carbon tetrachloride (CCl₄) and fed a high-fat diet (HFD). Pre-incubation with CISE significantly blocked the oxidative stress induced by t-BHP treatment in HepG2 cells (P < 0.05) and preserved the activities of catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase compared to group treated with t-BHP only. Similarly, the CCl₄- and HFD-induced reduction of antioxidant enzymes activities in liver was prevented by CISE treatment compared to control groups. Furthermore, hepatic lipid peroxidation were remarkably lower (P < 0.05) in the CISE-treated groups with t-BHP or HFD. To determine the active compound of CISE, the fractionation of CISE has been conducted and scoparone and scopoletin were identified as main compounds. These compounds were also shown to inhibit the t-BHP-induced ROS generation and reduction in antioxidant enzyme activity in an in vitro model system. From these results, it was demonstrated that CISE has the ability to protect against damage from oxidative stressors such as t-BHP, CCl₄ and HFD in in vitro and in vivo models. The CISE might be useful for the prevention of oxidative damage in liver cells and tissues.     

Hepatoprotective potentials of Phyllanthus amarus against ethanol-induced oxidative stress in rats

The hepatoprotective effect of methanolic extract of the leaf of Phyllanthus amarus (P. amarus) against ethanol-induced oxidative damage was investigated in adult male Wistar albino rats. P. amarus (250 and 500 mg/kg/day) and ethanol (5 g/kg/day, 20% w/v) were administered orally to animals for 4 weeks and 3 weeks, respectively. Ethanol treatment markedly decreased the level of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) in the liver, which were significantly enhanced by P. amarus treatment. Glutathione-S transferase (GST), which was increased after chronic ethanol administration, was significantly reduced by P. amarus treatment in the liver. Also, P. amarus significantly increased the activities of hepatic alanine transaminase (ALT) and aspartate transaminase (AST) as well as alkaline phosphatase (ALP), with a concomitant marked reduction in the plasma activity of the transaminases in the ethanol-challenged rats. Lipid peroxidation level, which was increased after chronic ethanol administration, was significantly reduced in the liver by P. amarus co-treatment. Results show that P. amarus leaf extract could protect the liver against ethanol-induced oxidative damage by possibly reducing the rate of lipid peroxidation and increasing the antioxidant defence mechanism in rats.     

Hepatoprotective activity of Chhit-Chan-Than extract powder against carbon tetrachloride-induced liver injury in rats

The capability of Chhit-Chan-Than extract powder (CCTEP, 10% aqueous Ocimum gratissimum L. extract) to protect against carbon tetrachloride (CCl₄)-induced oxidative stress and hepatotoxicity in vivo was investigated. Wistar rats were divided into five groups. Group A was a normal control group given only vehicle; Group B, the hepatotoxic group, was injected intraperitoneally twice a week with repeated 8% CCl₄/olive oil (0.1 mL/100 g of body weight); Groups C–E, extract-treated groups received CCl₄ and different doses of CCTEP (100 mg/kg and 200 mg/kg) or silymarin (200 mg/kg of body weight) daily by gavage for 8 weeks, respectively. The results showed that the CCl₄-induced histopathogical changes may be prevented by CCTEP through reducing the intercellular collogen stack, dropping blood serum alanine aminotransferase and aspartate aminotransferase levels, and restoring the catalase activity and glutathione content. The hepatoprotective properties were further confirmed by the marked improvement in histopathological examination and by quantitative steatosis-fibrosis scoring. The above results suggest that CCTEP is able to prevent the liver inflammation and fibrosis induced by repeated CCl₄ administration, and the hepatoprotective effects might be correlated partly with its antioxidant and free radical scavenging effects.     

Vitamin E deficiency enhances pulmonary inflammatory response and oxidative stress induced by single-walled carbon nanotubes in C57BL/6 mice

Exposure of mice to single-walled carbon nanotubes (SWCNTs) induces an unusually robust pulmonary inflammatory response with an early onset of fibrosis, which is accompanied by oxidative stress and antioxidant depletion. The role of specific components of the antioxidant protective system, specifically vitamin E, the major lipid-soluble antioxidant, in the SWCNT-induced reactions has not been characterized. We used C57BL/6 mice, maintained on vitamin E-sufficient or vitamin E-deficient diets, to explore and compare the pulmonary inflammatory reactions to aspired SWCNTs. The vitamin E-deficient diet caused a 90-fold depletion of alpha-tocopherol in the lung tissue and resulted in a significant decline of other antioxidants (GSH, ascorbate) as well as accumulation of lipid peroxidation products. A greater decrease of pulmonary antioxidants was detected in SWCNT-treated vitamin E-deficient mice as compared to controls. Lowered levels of antioxidants in vitamin E-deficient mice were associated with a higher sensitivity to SWCNT-induced acute inflammation (total number of inflammatory cells, number of polymorphonuclear leukocytes, released LDH, total protein content and levels of pro-inflammatory cytokines, TNF-alpha and IL-6) and enhanced profibrotic responses (elevation of TGF-beta and collagen deposition). Exposure to SWCNTs markedly shifted the ratio of cleaved to full-length extracellular superoxide dismutase (EC-SOD). Given that pulmonary levels of vitamin E can be manipulated through diet, its effects on SWCNT-induced inflammation may be of practical importance in optimizing protective strategies.     

Role of Nrf2 in preventing ethanol-induced oxidative stress and lipid accumulation

Oxidative stress and lipid accumulation play important roles in alcohol-induced liver injury. Previous reports showed that, in livers of nuclear factor erythroid 2-related factor 2 (Nrf2)-activated mice, genes involved in antioxidant defense are induced, whereas genes involved in lipid biosynthesis are suppressed. To investigate the role of Nrf2 in ethanol-induced hepatic alterations, Nrf2-null mice, wild-type mice, kelch-like ECH-associated protein 1-knockdown (Keap1-KD) mice with enhanced Nrf2, and Keap1-hepatocyte knockout (Keap1-HKO) mice with maximum Nrf2 activation, were treated with ethanol (5 g/kg, po). Blood and liver samples were collected 6 h thereafter. Ethanol increased alanine aminotransferase and lactate dehydrogenase activities as well as thiobarbituric acid reactive substances in serum of Nrf2-null and wild-type mice, but not in Nrf2-enhanced mice. After ethanol administration, mitochondrial glutathione concentrations decreased markedly in Nrf2-null mice but not in Nrf2-enhanced mice. H₂DCFDA staining of primary hepatocytes isolated from the four genotypes of mice indicates that oxidative stress was higher in Nrf2-null cells, and lower in Nrf2-enhanced cells than in wild-type cells. Ethanol increased serum triglycerides and hepatic free fatty acids in Nrf2-null mice, and these increases were blunted in Nrf2-enhanced mice. In addition, the basal mRNA and nuclear protein levels of sterol regulatory element-binding protein 1(Srebp-1) were decreased with graded Nrf2 activation. Ethanol further induced Srebp-1 mRNA in Nrf2-null mice but not in Nrf2-enhanced mice. In conclusion, Nrf2 activation prevented alcohol-induced oxidative stress and accumulation of free fatty acids in liver by increasing genes involved in antioxidant defense and decreasing genes involved in lipogenesis.     

Naltrexone effects on ethanol consumption and response to ethanol conditioned cues in C57BL/6 mice

RATIONALE: The conditions under which naltrexone reduces ethanol consumption and its effect on behavior controlled by ethanol conditioned stimuli remain unclear. OBJECTIVES: The objectives were to determine the effects of naltrexone on ethanol consumption by C57BL/6 (B6) mice when injected subcutaneously (expt 1) or delivered by osmotic minipump (expt 2), and on ethanol conditioned cues (expt 3). METHODS: Naltrexone effects on ethanol consumption and preference were measured in a continuous access two-bottle choice paradigm in groups of mice implanted with osmotic minipumps delivering 0-3.0 mg/kg per day or injected subcutaneously with 0-6.0 mg/kg doses. Naltrexone's (0-3.0 mg/kg) effect on ethanol-conditioned cues was indexed by its effect on the expression of ethanol place conditioning (expt 3). RESULTS: Naltrexone produced a transient reduction in ethanol consumption and a consistent reduction in preference when injected; however, it had no effect on ethanol consumption or preference when delivered continuously by osmotic minipump. Naltrexone attenuated the expression of ethanol place conditioning in a U-shaped dose-response function. CONCLUSIONS: The transient reduction in ethanol consumption produced by injected naltrexone and the absence of an effect when continuously delivered confirms a report that maintaining naltrexone at steady state levels may antagonize its attenuation of ethanol consumption. The reduced expression of ethanol place conditioning in naltrexone-injected mice suggests that the drug can attenuate the reinforcing effects of ethanol conditioned stimuli as was recently reported for lever responding maintained by ethanol conditioned stimuli in rats. These effects were observed at naltrexone doses with no readily apparent adverse side-effects, supporting its usefulness for treating alcoholism.     

Protective effect of aqueous Curry leaf (Murraya koenigii) extract against cadmium-induced oxidative stress in rat heart

Treatment of rats with a low dose of cadmium chloride caused a significant damage in the rat cardiac tissue indicated by the increase in the level of serum glutamate oxaloacetate transaminase and lactate dehydrogenase1 activities. Histological studies confirmed the damage due to cadmium. That cadmium-induced tissue damage was caused due to oxidative stress was evident from the changes observed in the levels of lipid peroxidation and reduced glutathione, the protein carbonyl content, and the alterations in the activities of cardiac antioxidant and pro-oxidant enzymes. Treatment of rats with cadmium also caused alterations in the activities of mitochondrial Kreb’s cycle as well as respiratory chain enzymes. All these changes were ameliorated when the rats were pre-treated with an aqueous extract of Curry leaf (Murraya koenigii). The studies indicated that the aqueous extract of Curry leaf protects the rat cardiac tissue against cadmium-induced oxidative stress possibly through its antioxidant activity. As curry leaf is consumed by people as part of their diet in India and South-East Asian and some European countries as well, and, as it has no reported side-effects, the results seem to have relevance at places where humans are exposed to cadmium environmentally or occupationally.     

Protective effect of the Aralia continentalis root extract against carbon tetrachloride-induced hepatotoxicity in mice

The root of Aralia continentalis Kitagawa has been used in traditional Korean medicine to relieve pain and to treat inflammation. The purpose of this study was to investigate the protective effects of the extract of A. continentalis roots (AC) against hepatotoxicity induced by carbon tetrachloride (CCl₄) and the mechanism of its hepatoprotective effect. In mice, pretreatment with AC prior to the administration of CCl₄ significantly prevented the increased serum enzymatic activity of ALT and AST as well as the formation of hepatic malondialdehyde. Histopathological evaluation of the livers also revealed that AC reduced the incidence of liver lesions induced by CCl₄. In addition, pretreatment with AC significantly prevented both the depletion of reduced glutathione (GSH) content and the decrease in glutathione-S-transferase (GST) activity in the liver of CCl₄-intoxicated mice. Hepatic GSH levels and GST activity were increased by treatment with AC alone. Heme oxygenase-1 (HO-1) is known to be induced by oxidative stress and to confer protection against oxidative tissue injuries. Interestingly, AC markedly upregulated hepatic HO-1 expression in CCl₄-treated mice, which might provide anti-oxidative activity in the liver. These results indicate that AC plays a critical protective role in CCl₄-induced acute liver injury by promoting anti-oxidative protein expression.     

Beneficial effects of Undaria pinnatifida ethanol extract on diet-induced-insulin resistance in C57BL/6J mice

This study was performed to evaluate the beneficial effect of Undaria pinnatifida ethanol extract (UEFx) on insulin resistance in diet-induced obese mice. A high-fat diet was supplemented with the UEFx at 0.69% (wt/wt) dose, which contains an equivalent amount of 0.02% fucoxanthin (wt/wt), or with Fx at 0.02% (wt/wt) dose in diet. After 9 weeks, both UEFx supplement significantly lowered the amount of visceral fat, the size of adipocyte, the fasting blood glucose concentration, the plasma insulin and the insulin resistance index similar to pure as shown by Fx supplement, compared to the high-fat (HF) control group. Blood glucose level was negatively correlated with hepatic glucokinase activity (r = −0.533, p < 0.05), whereas positively correlated with hepatic gluconeogenic enzyme activities (r = 0.463, p < 0.05 for glucose-6-phosphatase; r = 0.457, p < 0.05 for phosphoenolpyruvate carboxykinase). Ratio of hepatic glucokinase/glucose-6-phosphatase and glycogen content were significantly elevated by the UEFx and Fx supplements. Supplementation of the UEFx as well as Fx seemed to stimulate the β-oxidation activity and inhibit the phosphatidate phosphohydrolase activity resulting in a decrease in the hepatic lipid droplet accumulation. The results indicate that the UEFx can prevent insulin resistance and hepatic fat accumulation that is partly mediated by modulating the hepatic glucose and lipid homeostasis in the high fat-induced obese mice.     

Raphanus sativus extract protects against Zearalenone induced reproductive toxicity, oxidative stress and mutagenic alterations in male Balb/c mice

Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by several species of Fusarium in cereals and agricultural products. It has been implicated in several mycotoxicosis in farm animals and in humans. There is unequivocal evidence of reproductive toxicity of ZEN in male mice although the mechanism of action is unknown. Several reports suggest that exposure to ZEN resulted in oxidative stress, genotoxicity and perturbation of reproductive parameters. Therefore, the aim of the current study was to evaluate the protective effects of aqueous extract of Raphanus sativus growing in Tunisia against ZEN-induced reproductive toxicity and oxidative stress. Fifty male Balb/c mice were divided into five groups and treated for 28 days as follows: the control group, olive oil-treated groups, another treated with ZEN (40 mg/kg b.w), the last one treated with R. sativus extract alone (15 mg/kg b.w) and the other with ZEN + R. sativus extract. Testis samples were collected for the epididymal sperm count, testosterone concentration, and MDA level, GPx, CAT and SOD activities. Blood samples were collected for different biochemical analyses. Also, RAPD-PCR method was performed to assess the antigenotoxic effect of the extract in germ cells. The results indicated that ZEN-induced toxicological effects in accordance to those reported in the literature: decreasing in the sperm number, testosterone level and antioxidant enzyme status. The RAPD-PCR analysis revealed an alteration in the DNA bands patterns between control and ZEN-treated mice. The extract alone, rich in many antioxidant compounds, was safe and succeeded in counteracting the oxidative stress and protect against the toxicity resulting from ZEN.     

Phenolic extract of soybean (Glycine max) attenuates cisplatin-induced nephrotoxicity in rats

The present study investigated the modulatory role of phenolic extract of soybean (PESB) in a rat model of nephrotoxic acute renal failure induced by cisplatin. Cisplatin (2 mg/kg/day) was administered to the rats for 5 days and the animals were pretreated with PESB (250–1000 mg/kg). Blood urea nitrogen reduced by 49.8% and 59.0%, serum creatinine by 34.7% and 62.1% and urinary N-acetyl-β-d-glucosaminidase also decreased by 37.7% and 49.2% following treatment with 250- and 500-mg/kg doses of the extract respectively in the cisplatin-treated rats. The extract also significantly increased renal myeloperoxidase activity by 26.8% and 40.6% at these doses. PESB also decreased renal xanthine oxidase activity and serum nitrate/nitrite in the cisplatin-treated rats. In addition, PESB significantly attenuated the marked renal oxidative damage that accompanied cisplatin treatment. The extract improved liver histology and significantly increased the activities of the antioxidant enzymes measured [superoxide dismutase, catalase, glutathione-S-transferase], prevented glutathione depletion and decreased malondialdehyde level following cisplatin treatment. Furthermore, cisplatin-induced decrease in the activities of glucose-6-phosphatase and 5′-nucleotidase in these rats was attenuated only at 250 mg/kg dose of the extract. We concluded therefore that PESB via antioxidant and possibly anti-inflammatory actions offered protective benefit against cisplatin-mediated acute toxic injury to the kidney.     

Stimulatory effects of ethanol in C57BL/6 mice

Although ethanol stimulation is well documented in several species including humans, there is some controversy about whether the stimulation occurs in the highly inbred mouse strain, C57BL/6. Since inbred mouse strains are frequently used to elucidate mechanisms for individual differences in reaction to alcohol, the present study was undertaken to more completely characterize the behavioral effects of ethanol and to help resolve some of the controversy regarding the drug's stimulatory effect on C57 mice. Activity of female C57BL/6cr mice was assessed in either a lighted or dark environment for 20 min after injections of water or ethanol at doses of 0.5, 1.0, 2.0, 4.0 g/kg. Elevated activity (stimulation) was observed in mice injected with relatively low ethanol doses and tested in the light. The 2.0 g/kg dose produced a transient elevation in activity which declined rapidly across time. Animals tested under the dark condition were not stimulated by the drug but had activity reductions to high doses of ethanol. The detection of ethanol-induced stimulation appears to be related to the performance of control mice rather than a light-related difference in ethanol sensitivity.     

Antioxidant potential of tea reduces arsenite induced oxidative stress in Swiss albino mice

Environmental arsenic (As) is a potent human carcinogen and groundwater As contamination is a major health concern in West Bengal, India. Oxidative stress has been one of the prime factors in As-induced carcinogenicity. Generation of reactive oxygen species (ROS), beyond the body’s endogenous antioxidant balance cause a severe imbalance of the cellular antioxidant defence mechanism. Tea, a popular beverage has excellent chemopreventive and antioxidant properties. In this study it was investigated whether these flavonoids could ameliorate the arsenite (As III) induced oxidative stress in Swiss albino mice. Bio-monitoring with comet assay elicited that the increase in genotoxicity caused by As III was counteracted by both black tea and green tea. Elevated levels of lipid peroxides and protein carbonyl by As III were effectively reduced with green as well as black tea. They also exhibited protective action against the As III induced depletion of antioxidants like catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST) and glutathione (GSH) in mice liver tissue. Thus the tea polyphenols by virtue of their antioxidant potential may be used as an effective agent to reduce the As III induced oxidative stress in Swiss albino mice.     

Effects of the chestnut inner shell extract on the expression of adhesion molecules,fibronectin and vitronectin,of skin fibroblasts in culture

The inner shell of the chestnut (Castanea crenata S. et Z., Fagaceae) has been used as an anti-wrinkle/skin firming agent in East Asia, and preliminary experiments have found that a 70% ethanol extract from this plant material can prevent cell detachment of skin fibroblasts from culture plates. In order to examine the molecular mechanisms underlying this phenomenon, its effects on the expression of adhesion molecules, such as fibronectin and vitronectin, were investigated using the mouse skin fibroblast cell line, NIH/3T3. Using fixed-cell ELISA, Western blotting and immunofluorescence cell staining, it was clearly demonstrated that the chestnut inner shell extract enhanced the expression of the cell-associated fibronectin and vitronectin. Scoparone (6,7-dimethoxycoumarin), isolated from the extract, also possessed similar properties. These findings suggest that the enhanced expression of the adhesion molecules may be one of the molecular mechanisms for how the chestnut inner shell extract preventing cell detachment and may be also responsible for its anti-wrinkle/skin firming effect.     

Chromium(VI) induces oxidative stress in the mouse brain

Potassium dichromate was given to female Swiss mice (25 mg/kg per day) orally in water for 1–3 days. Brain homogenates were prepared to evaluate the occurrence of oxidative stress in this organ through the measurement of the antioxidant defense levels, and the extent of lipid peroxidation. In addition, mitochondrial fractions were isolated from brain homogenates to determine the production of reactive oxygen species in this subcellular fraction. The administration of potassium dichromate for 3 days caused increases of 72 and 74% in superoxide dismutase and catalase activities, respectively, in the homogenates. The treatment with this metal for 3 days increased brain homogenate chemiluminescence and thiobarbituric acid-reactive substances by 34 and 29%, respectively. The brain contents of the non-enzymatic antioxidants -tocopherol and sulfhydryl groups decreased by 35 and 32%, respectively. Ascorbic acid levels were not modified by the administration of potassium dichromate. Finally, there was a significant increment in the mitochondrial production of oxidants in the brain of treated mice as compared with controls. These results suggest that chromium(VI) produces an increased formation of reactive oxygen species and brain lipid peroxidation. The increase in the antioxidant enzyme activities reflects an adaptive response against oxidative stress, while the reduction in the levels of non-enzymatic antioxidants might be due to their reaction with reactive oxygen species generated during the metabolism of chromium(VI).     

Hepatoprotective effect of mulberry water extracts on ethanol-induced liver injury via anti-inflammation and inhibition of lipogenesis in C57BL/6J mice

Many plant extracts and their bioactive substances are well recognized for their potential to exert as chemoprotective agents against common alcoholic liver injury. In this study, the effects of Mulberry water extracts (MWE) treatment in the prevention of alcohol-induced liver injury were investigated in mice. MWE contain many nutrients and bioactive substances, including fifteen types of polyphenols and anthocyanin compounds. The parameters of histopathology, immunohistochemistry, antioxidant defense and proinflammatory mediator demonstrated the inhibitory effect of MWE on alcohol-induced liver injury. Plasma and hepatic content analysis showed that MWE inhibited the levels of liver injury biomarkers (AST, ALT and ALP), triglyceride (TG) and cholesterol (TC). Furthermore, treatment with MWE lessened the expression of lipid synthesis-related proteins, increased the p-AMPK/AMPK ratio and PPAR-α. Fatty acid oxidation and export via microsomal triglyceride transfer protein (MTP) were both activated as well as carnitine palmitoyltransferase-1 (CPT1). These results suggested that MWE prevents alcohol-induced liver injury through the activation of the AMPK and PPAR-α signal. This may be mediated by multiple pathways, including reduced lipid accumulation and lipid synthesis, increased fatty acid transport and fatty acid oxidation responses, decreased oxidative stress and facilitated anti-inflammation.     

Agrimonia eupatoria protects against chronic ethanol-induced liver injury in rats

This study examined the hepatoprotective effects of Agrimonia eupatoria water extract (AE) against chronic ethanol-induced liver injury. Rats were fed a Lieber–DeCarli liquid diet for 8 weeks. Animals were treated orally with AE at 10, 30, 100, and 300 mg/kg/day. After chronic consumption of ethanol, serum aminotransferase activities and pro-inflammatory cytokines markedly increased, and those increases were attenuated by AE. The cytochrome P450 2E1 activity and lipid peroxidation increased after chronic ethanol consumption, while reduced glutathione concentration decreased. Those changes were attenuated by AE. Chronic ethanol consumption increased the levels of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 protein expression, inducible nitric oxide synthase and cyclooxygenase-2 protein and mRNA expression, and nuclear translocation of nuclear factor-kappa B, which was attenuated by AE. Our results suggest that AE ameliorates chronic ethanol-induced liver injury, and that protection is likely due to the suppression of oxidative stress and TLR-mediated inflammatory signaling.     

Effects of exogenous metallothionein against thallium-induced oxidative stress in rat liver

Metallothionein (MT) is a low-molecular weight sulfur-rich protein that plays role in metal homeostasis/detoxification and radical scavenging. The following study investigated the ability of exogenous MT to protect against oxidative damage induced by thallium (TI) in rat liver. Male Wistar rats were divided into four groups; a control and three experimental groups. The control group received physiological saline. Group 1 animals were injected with thallium acetate intraperitoneally (i.p.) at a single dose of LD₅₀ (32 mg/kg). In group 2 and group 3, metallothionein I was administrated once at two different doses (1 or 2.5 mg/kg i.p., respectively) 1 h before TI intoxication. Levels of endogenous antioxidants, oxidative stress markers were measured and histopathological examinations were performed 4 days after TI administration. TI accumulation in liver decreased related to the dose of MT. Mostly all of the alterations in the levels antioxidants restored to normal levels in MT administrated animals. H₂O₂ levels and lipid peroxidation decreased, integrity of hepatocytes and membranous structures inside the cells were preserved. The toxic effects of TI were modulated in MT administrated animals particularly at the dose of 2.5 mg/kg. These findings suggest an active role of exogenous MT against TI-induced oxidative stress in rat liver.     

Ethanol intoxication and withdrawal among three age groups of C57BL/6NNIA mice

Data have not been forthcoming on the effects of chronic ethanol administration on intoxication and severity of withdrawal using animals representative of the life-span of a particular species. The purpose of this study was to examine ethanol intoxication and withdrawal among three age groups (3, 14, 25 months) of C57BL/6NNIA male mice. Ethanol was administered in a liquid diet for 14 days. Pair-fed control groups and laboratory chow groups were also employed. Blood ethanol levels, signs of intoxication and withdrawal, liquid diet consumption, and body weight were measured. Old mice were significantly more intoxicated than younger mice. However, young mice consumed more ethanol as compared to the older mice. Blood ethanol levels did not differ among the three age groups, although variability was high within each age group. The ethanol liquid diet groups did not show a decrease in body weight. Withdrawal was more severe for old animals than younger animals. The greater effects of ethanol observed in the old animals do not appear to be attributable to age differences in blood ethanol levels, amount of ethanol consumed, or body weight loss.