Fatty Liver Changes Research Articles

Opisthorchis viverrini infection causes liver and biliary cirrhosis in gerbils

Opisthorchis viverrini infection causes many hepatobiliary diseases, including cholangiocarcinoma. Hence, the study of O. viverrini infection in humans is subject to ethical limitations, so an animal model, the Syrian hamster, is often used. O. viverrini can develop into the adult stage not only in Syrian hamsters but also in other animals, including gerbils, but until now, there has been no report on pathology and susceptibility in gerbils. The present study revealed the pathology of O. viverrini infection in gerbils through gross appearance, histopathology, and worm recovery at various time points. Gerbils were infected with 50 O. viverrini metacercariae and then sacrificed at the time of observation. The gross appearance of the liver showed micronodules at the liver surface, suggesting liver and biliary cirrhosis. Light microscopic observation was correlated to the gross appearance with cholecystitis, fatty liver changes, fibrous septa, and generalized cirrhosis. The range of worm burden fluctuated from 1 to 25 worms with large body size, which was correlated with pathology. These novel findings indicate that O. viverrini infection can cause liver and biliary cirrhosis in gerbils, depending on the worm burden, worm size, and habitat.

Obesity, insulin and chemoresistance in colon cancer.

Obesity, insulin and chemoresistance in colon cancer.

Sitagliptin prevents the development of metabolic and hormonal disturbances, increased β-cell apoptosis and liver steatosis induced by a fructose-rich diet in normal rats

The aim of the present study was to test the effect of sitagliptin and exendin-4 upon metabolic alterations, β-cell mass decrease and hepatic steatosis induced by F (fructose) in rats. Normal adult male Wistar rats received a standard commercial diet without (C) or with 10% (w/v) F in the drinking water (F) for 3weeks; animals from each group were randomly divided into three subgroups: untreated (C and F) and simultaneously receiving either sitagliptin (CS and FS; 115.2mg/day per rat) or exendin-4 (CE and FE; 0.35 nmol/kg of body weight, intraperitoneally). Water and food intake, oral glucose tolerance, plasma glucose, triacylglycerol (triglyceride), insulin and fructosamine concentration, HOMA-IR [HOMA (homoeostasis model assessment) for insulin resistance], HOMA-β (HOMA for β-cell function) and liver triacylglycerol content were measured. Pancreas immunomorphometric analyses were also performed. IGT (impaired glucose tolerance), plasma triacylglycerol, fructosamine and insulin levels, HOMA-IR and HOMA-β indexes, and liver triacylglycerol content were significantly higher in F rats. Islet β-cell mass was significantly lower in these rats, due to an increase in the percentage of apoptosis. The administration of exendin-4 and sitagliptin to F animals prevented the development of all the metabolic disturbances and the changes in β-cell mass and fatty liver. Thus these compounds, useful in treating Type2 diabetes, would also prevent/delay the progression of early metabolic and tissue markers of this disease.

Aflatoxin in Chicken's Feed and it's Effects on Apoptosis

One hundred samples of ration, protein, corn, soybean, and wheat were collected from poultry houses in Baghdad and suburbs to examine Aflatoxin occurrence in chicken's diet. ALISA technique was used for this purpose.The results revealed presence of high level of Aflatoxin in ration (P< 0.05) compared with other contents of diet fallowed by soybean (P< 0.05) then corn, wheat, and protein respectively .These contents were mixed and tested by ELISA and presented to the experiment chicks. One hundred and twenty, one day old chicks, were divided to four groups, first group (G1) was fed contaminated Aflatoxin feed and did not vaccinated. The second group (G2) was fed contaminated feed and vaccinated with Newcastle Disease vaccine (NDV) and Infectious Bursal Disease vaccine (IBDV), whereas the third group (G3) was fed uncontaminated feed and vaccinated with NDV and IBDV, and the forth group (G4) -Control group- was fed uncontaminated feed and didn't vaccinated.After four days of the beginning of the experiment, blood, liver, and kidney samples were collected, and this procedure was repeated every four days to estimate total protein, haemagglutination inhibition (HI) test, ELISA test to detect (ND) antibody titer. Results showed decrease in total protein and (ND) antibodies in the groups which were fed contaminated feed.Liver and kidney samples were collected for histopathologic examination which showed vacculation, fatty change and hemorrhage in liver and kidney samples in addition to accumulation of lymphocytes. Condensing of Bauman capsule's tufts in kidney. Increased Kupher's cell in the liver. Apoptosis was noticed significantly in group one and group two, compared with group three and control. It was concluded that Aflatoxin in high concentration in chicken feed and feed contents was present, with negative impact of the toxin on ND vaccination and blood total protein, also affects the histology of liver and kidney.

Grape seed extract to improve liver function in patients with nonalcoholic fatty liver change

Background/Aim:Therapeutic interventions in nonalcoholic fatty liver disease are limited, while antioxidative materials have shown benefi ts in animal models. This study aimed to evaluate grape seed extract as an anti-oxidative material in this process. Therapeutic effects of grape seed extract were evaluated in comparison to vitamin C in a double-blind setting.Materials and Methods:Fifteen patients were enrolled in each group. Liver function tests were done; also, grade of steatosis and pattern of echogenicity of the liver were determined. Patients were followed up by the same evaluation repeated in first, second and third months.Results:Mean age ± standard deviation was 43.2 ± 10.3 years. Grape seed extract (GSE) significantly improved the grade of fatty liver change; and resulted in significant decrease in alanine aminotransferase in patients receiving the concentrate compared to those receiving vitamin C independently, from the initial grade of steatosis.Conclusions:This study describes the beneficial effect of using grape seed extract for three months in patients with nonalcoholic fatty liver disease. These results may improve with a longer period of follow-up.

Lindera erythrocarpa Makino extract reduces obesity induced by high-fat diet in rats

Lindera erythrocarpa Makino (LE) is widely distributed on Jeju Island, where it has been used for various traditional therapies. Effects of a crude extract of LE were examined in rats with obesity induced by a high-fat diet (HFD). Anti-obesity effects were followed in rats receiving orally administered vehicle, 100mg/kg extract, or 250 mg/kg LE extract, for 56 days. LE extract (250 mg/kg) suppressed increases in body weight and epididymal fat, with amelioration of fatty changes in the liver. Additionally, serum levels of alanine aminotransferase, aspartate aminotransferase, and total cholesterol were significantly decreased compared with those of vehicle-treated groups (p

Oral Toxicity of Agro-Fungicides: Tilt (Propiconazole), Bayleton (Triadimefon) And Their Mixture to Nubian Goats

Introduction: The hazard use of pesticides, emergence of many diseases with high prevalence e.g (cancer, kidney failure and hepatic problems) urged the need for research on fungicides which are continuously received by human in Sudan via fruit and vegetables.Objective: To detect the toxicity of these fungicides in experimental animals. Methods: Twelve Nubian goats were used in these experiments; they were grouped into three groups (and one control group) and dosed orally with two fungicides [Propiconazole (100mg/kg/day), Triadimefon (100mg/kg/day)] and their mixture (50:50 mg/kg/day). Animals were closely observed for clinical signs and behavior. Dead or slaughtered animals underwent postmortem examination and lesions were recorded. Samples from different organs were preserved for histopathological studies. Freshblood was collected for heamatological and Serobiochemical analysis.Results: Five minutes post-dosing, the animals showed some clinical signs which recovered after four hours. Death occurred in days 12- 25 in the animals dosed with the mixture. The most prominent feature in postmortem lesions was the congestion in different organs. Histopathological changes were the fatty change of liver and kidneys. In Triadimefon dosed group, the values of PCV, Hb and MCHC decreased significantly (p

Serum α-fetoprotein levels in liver steatosis

Nonalcoholic fatty liver disease (NAFLD) is a common disorder and becoming a leading cause of cirrhosis in the western world. The monitoring of the disease is challenging and the prognostic importance of α-fetoprotein (AFP) level elevation in NAFLD remains uncertain. Eighty-four patients were evaluated in the study. Patients with evidence of fatty liver in an abdominal ultrasonography performed for any reason were enrolled in the study. Degree of liver steatosis was graded into three groups. As a control group, patients without fatty liver or other liver diseases were included. All patients and controls were asked about prior hepatic diseases, consumption of alcohol, smoking, drug use, and a physical examination, biochemical analyses including liver function tests, different components of the metabolic syndrome, and the homeostasis model assessment-estimated insulin resistance (HOMA-IR) score were also performed. Body mass index, aspartate aminotransferase, alanine aminotransferase, glucose, insulin, and HOMA-IR in patients with NAFLD were higher than in control group. Triglyceride, total cholesterol, low-density lipoprotein, and high-density lipoprotein cholesterol levels were higher in NAFLD group than in control group. A statistically significant increase in AFP levels was noted in patients with NAFLD (4.09±1.68) when compared with healthy controls (2.95±0.41) (P<0.05). A statistically significant increase in AFP levels was noted in patients with grade 3 NAFLD (5.43±1.51) when compared with grade 1 (2.92±1.06) and grade 2 NAFLD groups (3.97±1.45). Also, AFP was significantly higher in grade 2 NAFLD group than in grade 1 NAFLD group. AFP was correlated with NAFLD grade, but neither ALT nor AST showed correlation. According to multivariate analysis, correlation between NAFLD grade and serum AFP levels was independent from the other factors. Patients with NAFLD have higher AFP levels than those without fatty liver changes. AFP levels rise as grade of liver steatosis increases. NAFLD should be among the differential diagnosis of elevated serum AFP levels.

Sonographic hepatic-renal ratio as indicator of hepatic steatosis: comparison with 1H magnetic resonance spectroscopy

The aim of this study was to determine the diagnostic performance of ultrasound (US) in the quantitative assessment of steatosis by comparison with proton magnetic resonance spectroscopy ( 1H-MRS) as a reference standard. Three liver echo-intensity indices were derived: US hepatic mean gray level, hepatic-renal echo-intensity ratio (H/R), and hepatic-portal blood echo-intensity ratio. The 1H-MRS degree of steatosis was determined as percentage fat by wet weight. Regression equations were used to estimate quantitatively hepatic fat content. The hepatic fat content by 1H-MRS analysis ranged from 0.10% to 28.9% (median value, 4.8%). Ultrasound H/R was correlated with the degree of steatosis on 1H-MRS ( R 2= 0.92; P < .0001), whereas no correlation with 1H-MRS was found for hepatic mean gray level and hepatic-portal blood echo-intensity ratio. A receiver operating characteristic curve identified the H/R of 2.2 as the best cutoff point for the prediction of 1H-MRS of at least 5%, yielding measures of sensitivity and specificity of 100% and 95%, respectively. In this pilot study, US H/R exhibits high sensitivity and specificity for detecting liver fatty changes. Our results indicate that quantitative evaluation of hepatic fat content can be performed using US H/R and could therefore be a valuable analytic tool in clinical investigation.

Quantification of Degree of Steatosis in Extended Criteria Donor Grafts With Standardized Histologic Techniques: Implications for Graft Survival

The gap between the availability of livers from organ donors and the increased demand has led many centers to apply strategies to reduce this deficit. Splitting of cadaveric organs for use in 2 recipients; domino transplantation; and organs from living donors, non–heart-beating donors, and extended-criteria donors (ECDs) are all currently used in orthotopic liver transplantation (OLT). Fatty changes in the donor liver are a risk factor for poor function after OLT; however, the presence of steatosis, frequently present in livers from ECDs, does not exclude the use of these organs. Since January 2000 at our institution, we observed 39 steatotic grafts that were stratified istologically as follows: low steatosis, 5% to 15%; mild steatosis, 16% to 30%; moderate steatosis, 31% to 60%; and severe steatosis (>60%). Histologic techniques can enable identification of the type of fatty change as macrovesicular and microvesicular. These alterations have different effects on primary nonfunction and primary dysfunction. Fifteen grafts, all with severe or moderate, macrovesicular changes were discarded. Twenty-four fatty grafts with low to moderate steatosis were utilized for transplant. Sections from 2 liver biopsies (1 wedge in the left lobe and 1 needle in the right lobe) were stained with hematoxylin-eosin, Masson trichrome, Gomori reticulin, and oil red O. The OLT was performed only in patients with a MELD (Model for End-Stage Liver Disease) score lower than 27. The rate of primary dysfunction was 12.5%, and of primary nonfunction 8.4%. The 6-month graft survival for all fatty livers was 80%. We encourage the careful use of grafts with low to moderate steatosis in recipients without additional risks.

Fatty liver in children.

The aim of this study is to investigate the clinical and laboratory characteristics of nonalcoholic fatty liver disease (NAFLD) in a referral center of pediatrics in the northwest of Iran. In this cross-sectional study all subjects aged between six months to 15 years that were referred to the sonography unit, were investigated for fatty liver from March 2005 to August 2006. Patients with fatty liver change underwent detailed clinical and laboratory evaluation. From 1500 children who were investigated, 34 subjects with sonographic evidence of fatty liver were enrolled in this study (2.3%). The mean age was 6.53 +/- 3.07 years. Elevated aspartate aminotransferase and alanine aminotransferase was detected in 38.2% and 47.1% of patients, respectively. The mean level of cholesterol was 461 +/- 182.23 mg/dl and 94.1% of patients had hypercholesterolemia. Total cholesterol level and serum aminotransferase levels had a significant positive correlation with severity of fatty liver (p < 0.05). Mean body mass index was significantly higher in patients with severe fatty liver (p < 0.05). The epidemiology of pediatric NAFLD should inform future attempts to develop evaluated screening protocols. Moreover, these data should guide efforts to delineate the pathophysiology of fatty liver in children.

Association between central venous pressure and blood loss during hepatic resection in 984 living donors

Although low central venous pressure (CVP) anesthesia has been used to minimize blood loss during hepatectomy, the efficacy of this technique remains controversial. We therefore assessed the association between blood loss and CVP during hepatic resection, and examined significant determinants associated with intraoperative hemorrhage during hepatectomy in living donors. Between April 2004 and April 2008, 984 living donors who underwent a hepatic resection were assessed retrospectively. Univariate and multivariate analyses were performed to explore the relationships between intraoperative blood loss and several variables including CVP. The mean intraoperative blood loss was 691.3 +/- 365.5 ml. Only four donors required packed red blood cell transfusions (mean, 1.5 U). The mean duration of hepatic resection was 92.1 +/- 26.3 min. The mean, maximum, and minimum values of CVP measured during hepatectomy were 4.6 +/- 1.7, 5.3 +/- 1.8, and 4.0 +/- 1.8 mmHg, respectively, and were not significantly correlated with intraoperative blood loss. On multivariate analysis, predictors of hemorrhage were liver fatty change, gender, and body weight, but none of the mean CVP, surgeons, anesthesiologists, anesthesia duration, resected liver volume, hepatectomy type, systolic blood pressure, heart rate, or body temperature were significant. CVP during hepatic resection was not associated with intraoperative blood loss in living liver donors, suggesting that CVP may not be an important factor in predicting blood loss during hepatectomy in healthy subjects.

The Correlation Between Sonographic Diagnosis and Laparoscopic Observations on Fatty Liver

Sonography is a comparatively cheap, convenient, and noninvasive testing on diagnosing fatty liver disease and with satisfied sensitivity and specificity. The sonographic diagnosis of fatty liver is usually made by radiologists who have few opportunities to observe the macroscopic changes on fatty liver. Having observed some obvious macroscopic changes of simple fatty liver in abdominal operations, we wanted to know how many morphological changes of the simple fatty liver there were in the end and what is the corresponding relationship between sonographic diagnosis and morphologic changes of the fatty liver. So, we designed this study for these destinations by using the intuitive and minimally invasive advantages of laparoscopy. For this study, we chose patients with benign cholecystic disease and simple fatty liver diagnosed by sonography. In the laparoscopic operations, the surface and periphery of the liver were observed and videotaped simultaneously. Liver biopsies were performed during the operations, and the specimen was analyzed by experienced pathologists postoperatively. The videos, histologic results, and the sonographic examinations on fatty liver were compared and tried to find some potential correlation among them. In this study, we found some common macroscopic changes of the fatty liver under laparoscopy, such as hepatomegaly, the dullness of the liver edge, the fatty infiltration of the liver surface, the texture of the liver changing from softness to tenacity, and the blood vessels of the liver surface becoming more fuzzy. According to the histologic results, the characteristics of different gradings of fatty liver under laparoscopy could be confimed. The statistical analysis revealed a higher consistency between sonographic diagnosis and laparoscopic macroscopic changes of the fatty liver. There are some typical features of the simple fatty liver under laparoscopy. These characteristics correspond to the sonographic diagnosis on the fatty liver. There is a high consistency between sonographic diagnosis and laparoscopic findings on the fatty liver. According to the macroscopic changes of the liver under laparoscopy, the extent of simple fatty liver could be evaluated under laparoscopy.

Qualitative and Quantitative Analysis of the Effects of Quinazolinones on Internal Organs of Newborn Balb/C Mice

Objective(s) Quinazolinones are heterocyclic compounds, with biological and pharmacological activities, such as inhibiting some proteins, enzymes and reducing blood lipids. Materials and Methods Following previous results of our group, effects of two new derivatives of quinazolinones 9(3)-quinazolinone-2-propyl-2-phenylethyl (QPPE) and 9(3)-quinazolinone-2-ethyl-2–phenylethyl (QEPE) on livers, intestines and kidneys of newborn Balb/C mice were investigated. Pregnant mice were divided into four groups of control, sham, experimental 1, treated with QPPE, and experimental 2, treated with QEPE. Experimental groups received 100 mg/kg body weight (most effective dose) of QPPE and QEPE, sham groups received methyl cellulose 0.05% (the solvent) and control groups received distilled water, intraperitoneally (IP), on day 8 of gestation. Five days after birth, livers, intestines and kidneys were removed, fixed in formalin 10%, stained with hematoxylene and eosin for histological and pathological studies. Results Results showed appearance of fatty changes in livers, an increase in diameters of hepatocytes and central veins of livers, and reduction in the lengths of villi of proximal, middle and distal segments of newborn Balb/C mice intestines. Furthermore, there was a diminished diameter of the lumen of the proximal tubules, and average diameter of the lumen of distal tubules which led to an increase in the number of glomeruli cells of newborn Balb/C mice kidneys. Conclusion Regarding inflammation in different parts of the kidneys, livers and intestines, our investigations suggest that quinazolinones may have some toxic effects on embryos.

Blood Lipid-Lowering and Antioxidant Effects of a Structured Lipid Containing Monoacylglyceride Enriched with Monounsaturated Fatty Acids in C57BL/6 Mice

We recently reported that a synthetic edible oil-containing monoacylglyceride (MAG) and diacylglyceride (DAG) exerted anti-atherosclerotic effects. In order to further investigate the activities and individual effects of MAG and DAG on the atherosclerotic process, we prepared a structured oil with various MAG and DAG contents and tested them both in vitro and in vivo, using C57BL/6 mice. The structured oil to be tested was mixed (final concentration 5%, wt/wt) with a high-cholesterol high-fat diet (1.2% cholesterol/15% fat/0.5% sodium cholate) and provided to the mice for 7 weeks. After administration, the mice consuming MAG97%-oil and DAG50%/MAG10%-oil evidenced 17% and 24% decreases in plasma total cholesterol (TC) level, respectively, as compared to a group of mice fed on lard. The experimental mice also had reduced plasma triglyceride concentrations and elevated high-density lipoprotein-cholesterol to TC ratios, by up to 31% in the case of the DAG50%/MAG10%-oil fed mice. The mice fed on MAG97%-oil exhibited elevated plasma antioxidant activity and lecithin:cholesterol acyltransferase activity. Histological assessments of the livers of the mice showed that the consumption of MAG-containing oil attenuated the adhesion of inflammatory cells and also ameliorated fatty liver changes, as compared to what was observed in the case of DAG85%-oil consumption. In conclusion, the MAG-containing oil exhibited anti-inflammatory and antioxidant activities in vivo, as well as in vitro inhibitory activity against human cholesteryl ester transfer protein. These results provide us with new insights into MAG-containing oil in terms of hypocholesterolemic effects and antioxidant activities.

Suppression of hepatic fat accumulation by highly purified eicosapentaenoic acid prevents the progression of d-galactosamine-induced hepatitis in mice fed with a high-fat/high-sucrose diet

The pathogenesis of non-alcoholic fatty liver disease (NAFLD) remains largely unknown. Here, we assessed the importance of hepatic fat accumulation on the progression of hepatitis. BALB/cA mice were fed with a standard diet (STD) or a high-fat and high-sucrose diet (HFHSD) for 14 days followed by intraperitoneal injection of d-galactosamine (DGalN) or vehicle. After 20–21 h, plasma and liver tissue were collected and analyzed. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in plasma were increased significantly in HFHSD-fed mice treated with DGalN compared to STD-fed mice treated with DGalN. This exacerbation by the HFHSD was also observed in the plasma soluble tumor necrosis factor receptor (sTNFR) levels, and hepatic levels of reactive oxygen species (ROS) and the fibrogenic gene expression, such as tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), connective tissue growth factor (CTGF) and osteopontin (OPN) in HFHSD-fed mice treated with DGalN. The triglyceride contents of the liver were significantly increased by the HFHSD. When eicosapentaenoic acid (EPA), a suppressor of sterol regulatory element binding protein 1 (SREBP-1), was administered to HFHSD-fed mice, the sensitivity of DGalN, as a result of plasma ALT and AST levels, was suppressed accompanied by reduced plasma sTNFR2 level and hepatic levels of triglyceride, ROS, and fibrogenic parameters, and by increased plasma adiponectin levels. These data suggest that the progression of steatotic liver injury closely depends on the accumulation of fat in the liver and is prevented by EPA through the suppression of the fatty liver change.

Analysis of hepatic gene expression during fatty liver change due to chronic ethanol administration in mice

Chronic consumption of ethanol can cause cumulative liver damage that can ultimately lead to cirrhosis. To explore the mechanisms of alcoholic steatosis, we investigated the global intrahepatic gene expression profiles of livers from mice administered alcohol. Ethanol was administered by feeding the standard Lieber–DeCarli diet, of which 36% (high dose) and 3.6% (low dose) of the total calories were supplied from ethanol for 1, 2, or 4 weeks. Histopathological evaluation of the liver samples revealed fatty changes and punctate necrosis in the high-dose group and ballooning degeneration in the low-dose group. In total, 292 genes were identified as ethanol responsive, and several of these differed significantly in expression compared to those of control mice (two-way ANOVA; p < 0.05). Specifically, the expression levels of genes involved in hepatic lipid transport and metabolism were examined. An overall net increase in gene expression was observed for genes involved in (i) glucose transport and glycolysis, (ii) fatty acid influx and de novo synthesis, (iii) fatty acid esterification to triglycerides, and (iv) cholesterol transport, de novo cholesterol synthesis, and bile acid synthesis. Collectively, these data provide useful information concerning the global gene expression changes that occur due to alcohol intake and provide important insights into the comprehensive mechanisms of chronic alcoholic steatosis.

Magnolia officinalis Reverses Alcoholic Fatty Liver by Inhibiting the Maturation of Sterol Regulatory Element–Binding Protein-1c

The generally accepted hypothesis for the pathogenesis of alcoholic liver disease (ALD) is the two-hit model, which proposes that fat accumulation in the liver increases the sensitivity of the liver to a second hit that leads to inflammatory liver cell damage. In this study we evaluated the effects of Magnolia officinalis (MO), which contains honokiol and magnolol as the primary pharmacological components, to eradicate fatty liver in rats fed an ethanol diet. In vitro studies showed that MO was able to protect RAW 264.7 cells from ethanol-induced production of tumor necrosis factor-α, reactive oxygen species, and superoxide anion radicals; the activation of NADPH oxidase; and subsequent cell death. We also investigated the therapeutic effects of MO on alcoholic fatty liver in Lieber-DeCarli ethanol diet–fed rats. MO treatment of the rats for the last 2 weeks of ethanol feeding completely reversed all the serum, hepatic parameters, and fatty liver changes. The increased maturation of sterol regulatory element– binding protein-1c in the liver by ethanol treatment was completely inhibited by treatment with MO. Therefore, MO may be a promising candidate for development as a therapeutic agent for ALD.[Supplementary Figures: available only at http://dx.doi.org/10.1254/jphs.08182FP]

Protective Effect of Dandelion Extracts on Ethanol-Induced Acute Hepatotoxicity in C57BL/6 Mice

Dandelion (Taraxacum officinale) has been widely used as an anti-inflammatory agent in oriental medicine. In the current study, we investigated the protective effect, and the possible mechanism, of dandelion extracts against ethanol-induced acute hepatotoxicity in C57BL/6 mice. Dandelion water and ethanol extract was administered at 2 g/㎏ body weight (BW) once daily for 7 consecutive days, whereas control and ethanol groups received water by gavage. Ethanol (50% ethanol; 6 g/㎏ BW) was administered 12 hr before sacrificing the mice in order to generate liver injury. Significantly increased serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities as well as liver triglyceride (TG) and cholesterol levels were attenuated by dandelion supplementation. In addition, dandelion extracts not only enhanced alcohol dehydrogenase (ADH) and anti-oxidative enzyme activities, but reduced lipid peroxidation. Cytochrome P450 2E1 (CYP 2E1), one of the critical enzymes xenobiotic metabolism, expression was lower with ethanol treatment but restored by dandelion supplementation. These results were confirmed by improved histopathological changes in fatty liver and hepatic lesions induced by ethanol. In conclusion, dandelion could protect liver against ethanol administration by attenuating of oxidative stress and inflammatory responses.

Temporal Changes in the Hepatic Fatty Liver in Mice Receiving Standard Lieber-DeCarli Diet.

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.