Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic administration of a soybean-derived polyenylphosphatidylcholine (PPC) extract prevents the development of cirrhosis in alcohol-fed baboons. To assess whether this phospholipid also affects earlier changes induced by alcohol consumption (such as fatty liver and hyperlipemia), 28 male rat littermates were pair-fed liquid diets containing 36% of energy either as ethanol or as additional carbohydrate for 21 d, and killed 90 min after intragastric administration of the corresponding diets. Half of the rats were given PPC (3 g/l), whereas the other half received the same amount of linoleate (as safflower oil) and choline (as bitartrate salt). PPC did not affect diet or alcohol consumption [15.4 +/- 0.5 G/(kg.d)], but the ethanol-induced hepatomegaly and the hepatic accumulation of lipids (principally triglycerides and cholesterol esters) and proteins were about half those in rats not given PPC. The ethanol-induced postprandial hyperlipemia was lower with PPC than without, despite an enhanced fat absorption and no difference in the level of plasma free fatty acids. The attenuation of fatty liver and hyperlipemia was associated with correction of the ethanol-induced inhibition of mitochondrial oxidation of palmitoyl-1-carnitine and the depression of cytochrome oxidase activity, as well as the increases in activity of serum glutamate dehydrogenase and aminotransferases. Thus, PPC attenuates early manifestations of alcohol toxicity, at least in part, by improving mitochondrial injury. These beneficial effects of PPC at the initial stages of alcoholic liver injury may prevent or delay the progression to more advanced forms of alcoholic liver disease.
 ...
PMID:Polyenylphosphatidylcholine attenuates alcohol-induced fatty liver and hyperlipemia in rats. 927 63

Socioeconomic development has led to a progressive increase of alcohol consumption in Taiwan, with an accompanying increase in alcohol-related psychiatric problems, traffic accidents, and liver disease. The prevalent rates of alcohol dependence for Han Chinese and Fomosan aborigines were 0.1% and 1%, respectively in 1950. The rate of alcohol dependence increased to 23% for aborigines in 1995. The number of cases of death and serious injuries due to alcohol-related traffic accident has decreased, and the number of fatalities resulting from these accidents has decreased from third to eighth since the inception of a program of random traffic stops with alcohol breath test in 1997. Alcohol liver disease (ALD) was defined as daily alcohol consumption of 60 g, for a duration of longer than 5 years. We classified ALD patients into two groups: (1) those whose average daily consumption of alcohol exceeded 120 g for a duration longer than 15 years (group A); and (2) all other patients (group B). The case records of 33 cases of biopsy-confirmed ALD were obtained for study. The average of daily alcohol consumption in these cases was 160 g. All but one of these patients were male, age ranged from 26 to 69 years, with an average of 43.1. Clinically, ill-defined gastrointestinal symptoms were the most common presentation (61%), and hepatomegaly was the main physical sign (73%). The average mean corpuscular volume values of ALD and non-ALD patients were 102.3 +/- 10.94 and 94.5 +/- 8.1, respectively (p < 0.01). The mean corpuscular volume values of group A and group B were 102.9 +/- 9.7 vs. 96.5 +/- 9.11 (p < 0.05). Result from serum SGOT/SGPT and gamma-glutamyltransferase/alkaline phosphatase for ALD and non-ALD revealed statistically significant differences between these groups. Using the avidin-biotin complex technique, tissue IgA deposition for ALD patients was found to be different from that of non-ALD patients. Ten of 13 ALD patients vs. 2 of 13 non-ALD patients had continuous-form IgA deposition. Histologically, 45.5% of ALD patients had alcoholic cirrhosis, whereas alcoholic hepatitis was present in only 9.1% of patients. Overall, 88% of cases showed various severity of fatty metamorphosis.
Alcohol Clin Exp Res 1998 05
PMID:Alcohol-related problems in Taiwan with particular emphasis on alcoholic liver diseases. 962 97

Compounds that cause peroxisome proliferation in rats and mice have been reported to interfere with mitochondrial (mt) bioenergetics and possibly biogenesis. The purpose of this investigation was to establish whether proliferation of peroxisomes and mitochondria are necessarily related. Perfluorooctanesulfonate (PFOS) and N-ethyl perfluorooctanesulfonamido ethanol (N-EtFOSE) were investigated as peroxisome proliferators in comparison to perfluorooctanoic acid (PFOA). Three parameters were chosen to assess peroxisome proliferation, stimulation of lauroyl CoA oxidase activity, reduction of serum cholesterol concentration, and hepatomegaly. mt Biogenesis was assessed through cytochrome oxidase activity, cytochrome content and mitochondrial DNA (mtDNA) copy number. PFOA, PFOS, or N-EtFOSE was administered via a single i.p. injection at 100 mg/kg in male rats, and measurements were made 3 days later. In this model, PFOS and PFOA share similar potencies as peroxisome proliferators, whereas N-EtFOSE showed no activity. mt Endpoints were altered only in the PFOA treatment group, which consisted of a decrease cytochrome oxidase activity in liver tissue and an increase in the mtDNA copy number. None of the perfluorooctanoates significantly altered mt cytochrome content following acute in vivo treatment. These data demonstrate that acute administration of PFOS or PFOA causes hepatic peroxisome proliferation in rats. However, stimulation of mt biogenesis is not a characteristic response of all peroxisome proliferators.
 ...
PMID:Perfluorooctanoate, perflourooctanesulfonate, and N-ethyl perfluorooctanesulfonamido ethanol; peroxisome proliferation and mitochondrial biogenesis. 1187 71

Diabetes is associated with ventricular dysfunction. Ethanol consumption increases the risk of cardiovascular disease among diabetics. Acetaldehyde (ACA), the main ethanol metabolite, depresses cardiac contraction and contributes to ethanol-induced cardiac dysfunction. This study examined the influence of gender and diabetes on ACA-induced myocardial dysfunction. Adult male and female rats were made diabetic with streptozotocin (55 mg/kg). Left ventricular papillary muscles were isolated and stimulated to contract at 0.5 Hz. The mechanical parameters measured were peak tension development, time-to-peak tension (TPT), time-to-90% relaxation (RT90), and maximum velocities of tension development and decline (+/-VT). TPT and RT90 were comparably similar between genders. The +/-VT appeared to be slower in myocardium from female rats when compared to that of male counterparts, although the difference was not significant. Experimental diabetes elicited severe hyperglycemia, cardiac hypertrophy, hepatomegaly, and renal hypertrophy in both male and female animals. Myocardial mechanical properties exhibited prolonged TPT and RT90 in diabetic myocardium from both genders. The +/-VT was significantly reduced by diabetes in male but not in female myocardium. Acute ACA exposure decreased myocardial tension development and the +/-VT and shortened TPT and RT90 in myocardium from normal and diabetic rats of both genders. The ACA-induced depressant response on tension development was slightly enhanced by the diabetic state. In conclusion, these data suggest that the development of diabetes-induced myocardial dysfunction is similar between male and female animals and that the ACA-induced myocardial depressant action may be affected by diabetes but not by gender.
 ...
PMID:The influence of gender, diabetes, and acetaldehyde on the intrinsic contractile properties of isolated rat myocardium. 1221 95

Adiponectin has recently been shown to be a promising candidate for the treatment of obesity-associated metabolic syndromes. Replenishment of recombinant adiponectin in mice can decrease hyperglycemia, reverse insulin resistance, and cause sustained weight loss without affecting food intake. Here we report its potential roles in alcoholic and nonalcoholic fatty liver diseases in mice. Circulating concentrations of adiponectin decreased significantly following chronic consumption of high-fat ethanol-containing food. Delivery of recombinant adiponectin into these mice dramatically alleviated hepatomegaly and steatosis (fatty liver) and also significantly attenuated inflammation and the elevated levels of serum alanine aminotransferase. These therapeutic effects resulted partly from the ability of adiponectin to increase carnitine palmitoyltransferase I activity and enhance hepatic fatty acid oxidation, while it decreased the activities of two key enzymes involved in fatty acid synthesis, including acetyl-CoA carboxylase and fatty acid synthase. Furthermore, adiponectin treatment could suppress the hepatic production of TNF-alpha and plasma concentrations of this proinflammatory cytokine. Adiponectin was also effective in ameliorating hepatomegaly, steatosis, and alanine aminotransferase abnormality associated with nonalcoholic obese, ob/ob mice. These results demonstrate a novel mechanism of adiponectin action and suggest a potential clinical application of adiponectin and its agonists in the treatment of liver diseases.
 ...
PMID:The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice. 1284 63

The mechanisms underlying alcoholic liver disease are not completely understood, but lipid accumulation seems to be central to the cause of this disease. The peroxisome proliferator-activated receptor alpha (PPARalpha) plays an important role in the control of lipid homeostasis, metabolism of bioactive molecules, and modulation of inflammatory responses. To investigate the roles of PPARalpha in alcoholic liver injury, wild-type and PPARalpha-null mice were continuously fed a diet containing 4% ethanol, and liver injury was analyzed. PPARalpha-null mice fed ethanol exhibited marked hepatomegaly, hepatic inflammation, cell toxicity, fibrosis, apoptosis, and mitochondrial swelling. Some of these hepatic abnormalities were consistent with those of patients with alcoholic liver injury and were not found in wild-type mice. Next, the molecular mechanisms of ethanol-induced liver injury in PPARalpha-null mice were investigated, and changes related to ethanol and acetaldehyde metabolism, oxidative stress, inflammation, hepatocyte proliferation, fibrosis, and mitochondrial permeability transition activation occurred specifically in PPARalpha-null mice as compared with wild-type mice. In conclusion, these studies suggest a protective role for PPARalpha in alcoholic liver disease. Humans may be more susceptible to liver toxicity induced by ethanol as PPARalpha expression in human liver is considerably lower compared to that of rodents.
 ...
PMID:Peroxisome proliferator-activated receptor alpha protects against alcohol-induced liver damage. 1538 58

Non-alcoholic fatty liver disease (NAFLD) is common in obesity. However, weight reduction alone does not prevent the progression of NAFLD to end-stage disease associated with the development of cirrhosis and liver disease. In a previous experiment, 50% ethanol extract of Acanthopanax senticosus stem bark (ASSB) was found to reduce body weight and insulin resistance in high fat diet-induced hyperglycemic and hyperlipidemic ICR mice. To evaluate the anti-steatosis action of ASSB, insulin-resistant ob/ob mice with fatty livers were treated with ASSB ethanol extract for an 8 week-period. ASSB ethanol extract reversed the hepatomegaly, as evident in reduction of % liver weight/body weight ratio. ASSB ethanol extract also specifically lowered circulating glucose and lipids, and enhanced insulin action in the liver. These changes culminated in inhibition of triglyceride synthesis in non-adipose tissues including liver and skeletal muscle. Gene expression studies confirmed reductions in glucose 6-phosphatase and lipogenic enzymes in the liver. These results demonstrate that ASSB ethanol extract is an effective treatment for insulin resistance and hepatic steatosis in ob/ob mice by decreasing hepatic lipid synthesis.
 ...
PMID:Acanthopanax senticosus reverses fatty liver disease and hyperglycemia in ob/ob mice. 1702 51

Chronic ethanol consumption is associated with serious and potentially fatal alcohol-related liver injuries such as hepatomegaly, alcoholic hepatitis and cirrhosis. Moreover, it has been documented that the clinical progression of alcohol-induced liver damage may be associated with an increase in hepatocellular death that involves apoptotic mechanisms. Although much information has been learned about the clinical manifestations associated with alcohol-related diseases, the search continues for a better understanding of the molecular and/or cellular mechanisms by which ethanol exerts its deleterious effects such as the induction of pro-apoptotic mechanisms and related cell damaging events. As part of the effort to enhance our understanding of those particular cellular pathways and mechanisms associated with ethanol toxicity, researchers over the years have utilized a variety of model systems. Recently, work has come forth demonstrating the utility of a hybrid cell line (WIF-B) as a cell culture model system for the study of alcohol-associated alterations in hepatocellular mechanisms. Success with such emerging model systems could aid in the development of potential therapeutic treatments for the prevention of alcohol-induced apoptotic cell death that may ultimately serve as a significant target in delaying the onset and/or progression of clinical symptoms of alcohol-mediated liver disease. This review article summarizes the current understanding of ethanol-mediated modifications in cell survival and thus the promotion of pro-apoptotic events with emphasis on analyses made in various experimental model systems, particularly the more recently characterized WIF-B cell system.
 ...
PMID:Effect of ethanol on pro-apoptotic mechanisms in polarized hepatic cells. 1785 38

Alcohol- and drug-related deaths remain a major problem in the UK. Although the pathological findings of cardio-, hepato- and splenomegaly are frequently and empirically associated with chronic alcohol and drug use, there is limited published evidence available. This study hypothesises that organomegaly is associated with chronic substance use, and may represent a prognostic indicator. The weights of hearts, livers and spleens from 280 chronic alcoholics (CA) and 33 chronic drug users (CD) were compared to those of 291 controls. Using a forensic pathology database, CA and CD subjects were identified from 4708 autopsies (January 2003-June 2006) by identifying adult cases with no known coexistent diseases. The controls were non-substance users and previously healthy adults who died of traumatic injuries. Alcohol misuse was associated with cardiomegaly (27% vs. 19%, male CA vs. control) and hepatomegaly (38% vs. 15%). Majority of cases had only one organ affected. In CA, occurrence of hepatomegaly was associated with death at a younger age (female mean age 47+/-9.4, p<0.009, male mean age 50+/-11.6, p<0.007). This study demonstrated an association between cardiomegaly and hepatomegaly with chronic alcohol misuse and identifies the potential role of hepatomegaly as a determinant of poorer outcome in chronic alcohol misusers.
 ...
PMID:Heart, liver and spleen pathology in chronic alcohol and drug users. 1831 8

All psychiatric and general medical male patients referred to 2 hospitals in Basra, Iraq from September 2000 to April 2001 were screened using the Alcohol Use Disorder Identification Test. A total of 189 men were identified as having alcohol-related problems. The majority were aged 30-49 years, and two-thirds had drunk alcohol for over 10 years. About 53% of patients exceeded 1 bottle (750 mL) of spirits daily, and 14.8% reported morning drinking. Elevation of liver enzymes, hepatomegaly, jaundice and cirrhosis were identified in 46.0%. Liver cirrhosis was more common in patients drinking locally made arak. Many of the patients suffered psychiatric disorders, including anxiety disorders, depression and suicide attempts, and 80.9% took other psychoactive drugs.
 ...
PMID:Clinical and biochemical profile of alcohol users in Basra. 2021 36


<< Previous 1 2 3 4 5 6 Next >>