• Toxicological Research
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• v.24 no.2
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• pp.113-117
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• 2008

Chronic exposure to ethanol induces cumulative damage to the liver starting from fatty infiltration to cirrhosis depending on the dose and duration of exposure. The whole process leading to the development of alcoholic liver disease is very complex and the mechanisms involved are not fully understood. Among many experimental animal models, Lieber-DeCarli liquid diet provides moderate to severe pathophysiological outcome depending on the compositional changes. In the present study, we investigated the temporal changes in the early phase hepatic disease in rats fed with standard Lieber-DeCarli diet. Male Wistar rats were fed with Lieber-Decarli ethanol diet for 6 weeks and the liver samples were obtained after 2, 4 and 6 weeks. Mild fatty infiltration was observed in 2 weeks of feeding and it became evident in 4 and 6 week samples. The level of hepatic triglyceride showed a good agreement with the data obtained in the pathological analysis. Feeding mice with ethanol diet resulted in the maturation and translocation of SREBP-1 to nucleus in the liver. Western blot analysis of the pooled liver sample of control and ethanol fed animals showed a clear-cut time-dependent increase in the expression of nSREBP-1. These data provide important information for selecting proper time point in experimental intervention study in the field of drug development for alcoholic liver disease.

• YAKHAK HOEJI
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• v.50 no.4
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• pp.254-262
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• 2006

This study had been done for the investigation of the effect of Vitis vinifera extract(V), Schisandra chinensis extract (S), Taraxacum officinale extract (T), Gardenia jasminoides extract (G), Angelica acutiloba extract (A) and Paeonia japonica extract (P), and their mixtures on the antioxidant and ethanol oxidation system which was induced by Lieber-DeCarli ethanol liquid diet. Male Sprague-Dawley rats were randomly divided into eight groups: ethanol diet (ED), normal diet (ND), ED+V (100 mg/kg/day), ED+S, ED+T, ED+G, ED+A and ED+P (300 mg/kg/day). We studied the effect on alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) after herbal extracts administration for 6 weeks in rats induced by Lieber-DeCarli ethanol liquid diet. The differences in ADH and ALDH activity of the rats treated with herbal extracts and ED group were not significant. Phase I enzyme activity was found to be significantly higher in the ED+V than the ED group. Phase II enzymes (glutathione-S-transferase, phenol sulfatransferase) activities were found to be higher in the herbal extracts than the ED group. Herbal extracts not only reduced ethanol-induced elevation of level malondialdehyde but also protected against ethanol-induced decrease of reduced glutathione, gluthione reducatse, glutathione peroxidase, catalase and superoxide dismutase activities. Therefore, they can be utilized as a health functional food or new drug candidate for fatty liver and hepatotoxicity which was induced by chronic alcohol consumption.

• Journal of Nutrition and Health
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• v.49 no.6
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• pp.420-428
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• 2016

Purpose: In this study, we investigated the effects of Cirsium setidens ethanolic extract (CS) on the development of alcoholic fatty liver and associated injury. Methods: Sprague-Dawley male rats were fed either Lieber-DeCarli control (C) or ethanol (35.5% of total calories) liquid diet with 0 (E), 100 mg/kgBW CS (E+LCS), or 500 mg/kgBW CS (E+HCS) for 8 weeks. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities as well as TG and cholesterol concentrations in the serum and liver tissues were measured by colorimetric assays. Liver histopathology was examined by Hematoxylin-eosin staining of the fixed liver tissues. Protein levels of phosphorylated-AMP activated protein kinase (p-AMPK), phosphorylated-acetyl CoA carboxylase (p-ACC), phosphorylated-nuclear factor kappa B (p-$NF{\kappa}B$), and $TNF{\alpha}$ were measured by Western blot analyses. Results: Both doses of CS markedly suppressed alcohol-induced lipid droplets accumulation in the liver tissues and significantly inhibited alcohol-induced increases in activities of serum ALT and serum AST. Similarly, CS significantly reduced hepatic and serum TG concentrations. Compared to groups fed alcohol only, CS supplementation strongly increased hepatic levels of p-AMPK and p-ACC. Further, CS significantly inhibited alcohol-induced phosphorylation of $NF{\kappa}B$, which was associated with reduced hepatic protein levels of $TNF{\alpha}$. Conclusion: Our data demonstrated that CS has a protective effect against alcoholic liver injury, which was associated with activation of AMPK and inhibition of $NF{\kappa}B$.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.1
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• pp.57-64
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• 2012

Cherry silverberry (Elaeagnus multiflora) contains bioactive phenolics. This study was conducted to determine whether feeding cherry silverberry wine (CSW) to rats would alleviate the progress of alcoholic fatty liver. Adult male Sprague-Dawley rats were divided by weight into the following three groups. Two groups of rats were fed 6.7% ethanol or the caloric equivalent Lieber-DeCarli diet containing maltose-dextrin, and the other group an isocaloric Lieber-DeCarli diet containing CSW at the same ethanol level for 6 weeks. CSW's flavonoids, its antioxidant and free radical scavenging activities, serum transaminases, serum and hepatic lipids, and liver histology were examined. Our results showed that CSW exerted significant antioxidant and radical scavenging activities. The serum activities of alanine and aspartate transminases were markedly decreased by CSW at 6 weeks. Also, CSW feeding resulted in significant reductions in blood cholesterol and triglyceride. The development of alcoholic fatty liver was significantly delayed by lowering fat accumulation. Taken together, these results indicate that CSW may help protect the liver against alcoholic fatty liver by improving serum and hepatic lipid status. This may be associated with the protective effect of CSW on alcoholic fatty liver via bioactive phenolic compounds.

• Journal of Ginseng Research
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• v.41 no.4
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• pp.503-512
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• 2017

Background: Chronic heavy alcohol consumption may raise the risk of developing type 2 diabetes mellitus. Saponins inhibit apoptosis of pancreatic islet cells and reduce lipid parameters. The present study was designed to investigate the effect of saponin on chronic ethanol-treated diabetic rats. Methods: Long-Evans Tokushima Fatty (LETO) and Otsuka Long-Evans Tokushima Fatty (OLETF) rats were pair-fed a Lieber-DeCarli diet with and without 5% ethanol for 12 wks. Two weeks after starting the pair-feeding with the Lieber-DeCarli diet, intraperitoneal injection of saponin was performed for 10 wks. To perform the experiments, rats were divided as follows: LETO-Control (LC), LETO-Ethanol (LE), LETO-Ethanol-Saponin (LES), OLETF-Control (OC), OLETF-Ethanol (OE), and OLETF-Ethanol-Saponin (OES). Results: The weights of epididymal and mesenteric fat tissue in LES and OES rats were the lightest from among the LETO and OLETF groups, respectively. The secretion of alanine aminotransferase and cholesterol in OES rats decreased significantly compared to their secretion in OC and OE rats, respectively. The islets of the pancreas in LE and OE rats showed clean, unclear, and smaller morphology compared to those of LC, LES, OC, and OES rats. In addition, the expression of insulin in the islets of the pancreas in LC, LES, OC, and OES rats was higher than in LE and OE rats. Conclusion: Saponin may not only be helpful in alleviating the rapid progress of diabetes due to chronic alcohol consumption in diabetic patients, but may also show potential as an antidiabetic drug candidate for diabetic patients who chronically consume alcohol.

• Journal of Nutrition and Health
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• v.29 no.7
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• pp.721-728
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• 1996

The level of oxidative tissue damage caused by free radicals generated from ethanol oxidation was determined in the myocardium of chronic ethanol fed-rats and the protective action of various radical scavenging enzymes was monitored, also. Adult male Sprague-Dawley rats were given ethanol in an amount of 36% of total calories via Lieber-DeCarli liquid diet for 6 weeks. Control group was pair-fed with the diet containing isocaloric amount of dextrin-maltose instead of ethanol. Chronic ethanol administration resulted in the increased amount of myocardial thiobarbituric acid reactive substance(TBARS), th parameter of lipid peroxidation, under our experimental condition. Chronic ethanol ingestion did not cause any change in activities of either glutathione peroxidase or glutathione reductase and glucose-6-phosphate dehydrogenase were decreased after ethanol treatment. Therefore, chronic ethanol administration seemed to cause considerble changes in cellular defense function against oxidative tissue damage in rat myocardium through glutathione utilizing system and radical generation system. However the ultimate net result of chronic ethanol inestion on the myocardium of rat was the oxidative tissue damage revealed by increased TBARS content.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.2
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• pp.187-193
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• 2014

This study investigated whether or not Citrus unshiu peel extract (CPE) affects fat accumulation in livers of rats fed an ethanol-containing liquid diet. Initially, male Sprague-Dawley rats were housed individually in stainless steel, wire-bottomed cages with free access to a Lieber-Decarli control liquid diet. Rats were divided by body weight into three groups of eight each: one group of rats was fed the Lieber-Decarli control liquid diet devoid of ethanol (control), another was fed the Lieber-Decarli ethanol diet (ethanol), and third was fed the same ethanol diet except containing CPE. All three groups were fed their respective diets for 6 weeks. Serum and liver lipids were analyzed and liver histology performed. Body weight did not differ among the groups over the 6-wk duration. Histology images showed that CPE administration significantly improved fat accumulation in livers, which was induced by ethanol diet. Serum levels of transaminases and lipids also were reduced by CPE consumption. Taken together, the results indicate that CPE may protect ethanol-induced fatty liver by lowering fat accumulation in both the liver and blood. The protective effects of CPE appear to be due to its phenolic contents.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.4
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• pp.467-473
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• 2016

This study was designed to investigate whether consumption of onion wine can reduce serum biomarkers of ethanol-induced fatty liver in rats. Male Sprague-Dawley rats were initially trained for meal feeding to prevent reduction of food intake. After the training period, rats were weight-matched and assigned to the following three groups: 1) a control group fed a control liquid diet containing maltose-dextrin, 2) an ethanol group fed an ethanol liquid diet with 95% ethanol, and 3) an onion wine group fed the same ethanol liquid diet but containing onion wine extract at 1 mL/d/group. All three groups were fed daily for 6 weeks. At 0, 3, and 6 weeks, blood was collected via the orbital sinus following overnight food deprivation and terminally organs collected. Blood lipids and transaminase activities significantly increased in the ethanol-fed group but significantly reversed in the onion wine-fed group. The hepatic levels of fat and cholesterol at 6 weeks were significantly elevated by ethanol administration but significantly reduced by onion wine. These findings indicate that onion wine may ameliorate ethanol-induced fatty liver by lowering hepatic and blood lipid levels.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.11
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• pp.1548-1555
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• 2011

Persimmons are shown to contain high levels of phenolics. The present study was designed to investigate if a sweet persimmon wine (SPW) would affect the development of alcoholic fatty liver in rats. Initially, male Sprague-Dawley rats were housed singly in stainless steel wire-bottomed cages in a room of controlled temperature and lighting. The rats had free access to a nutritionally adequate AIN-93G diet and deionized water. After the acclimatization period, rats were weight-matched and assigned to the following three groups: two groups were fed 6.7% ethanol or the caloric equivalent of maltose-dextrin in a Lieber-DeCarli diet and the other group was fed the isocaloric Lieber-DeCarli diet containing SPW at the same ethanol level. All three groups were fed their respective diets for 6 weeks. Serum transaminase, cholesterol, and triglyceride levels were measured. Liver lipids and histology were assessed at 6 weeks. The total phenolic content and the antioxidant and free radical scavenging activities of SPW were determined. SPW significantly increased antioxidant and free radical scavenging activities. As markers of liver injury, serum alanine and aspartate transminases were markedly lowered by SPW at 6 weeks. SPW significantly reduced the serum levels of serum cholesterol and triglyceride compared to ethanol treatment. SPW delayed the development of an alcoholic fatty liver by reversing fat accumulation in the liver, as evidenced in histological observations. Taken together, SPW seems to protect the liver from becoming fatty by alleviating fatty liver symptoms and lowering hepatic and serum lipid levels. Such a protective effect of SPW appears to be in part due to its phenolics.

• Journal of Nutrition and Health
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• v.40 no.5
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• pp.413-418
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• 2007

The present study was designed to observe the effect of chronically ingested ethanol on the level of fatty acid ethyl esters (FAEEs), which is a non-oxidative metabolite of ethanol metabolism in tissues, and its correlation to the status of oxidative stress in rats. Forty male Sprague Dawley rats weighing 145 - 155 g were divided into 2 groups, Control and EtOH. All rats were fed Lieber-DeCarli liquid diet for 4 weeks by pair-feeding. An isocaloric maltose dextrin was added in replace of 50 g ethanol (36%kcal) in the control diet. Chronically ingested ethanol significantly increased the content of FAEEs in pancreas and liver, but not in brain. The level of 2-thiobarbituric acid reactive substances (TBARS) was significantly increased, but ${\alpha}-tocopherol$ level was significantly decreased in pancreas and liver. However, the levels of TBARS and ${\alpha}-tocopherol$ in brain were not significantly affected by ethanol ingestion. Therefore, chronically ingested ethanol might cause tissue damage by increasing the levels of FAEEs and TBARS and dissipating more ${\alpha}-tocopherol$ in tissues.