Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper reviews phytonutrients from rice bran that have shown promising disease-preventing and health-related benefits in experimental research studies. Candidate products studied and under investigation include: inositol and related compounds, inositol hexaphosphate (IP6 or phytate), rice oil, ferulic acid, gamma-oryzanol, plant sterols, tocotrienols and RICEO, a new rice-bran-derived product. Diseases in which preventive and/or nutraceutical effects have been detected include: cancer, hyperlipidemia, fatty liver, hypercalciuria, kidney stones, and heart disease. In addition, rice-bran products may have potential applications as nutritional ingredients in the context of their utility in functional foods.
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PMID:Rice-bran products: phytonutrients with potential applications in preventive and clinical medicine. 1127 26

The mechanism of hepatocarcinogenesis in hepatitis C virus (HCV) infection is still undefined. One possibility is the involvement of oxidative stress, which can produce genetic mutations as well as gross chromosomal alterations and contribute to cancer development. We recently showed that after a long period, the core protein of HCV induces hepatocellular carcinoma (HCC) in transgenic mice with marked hepatic steatosis but without inflammation, indicating a direct involvement of HCV in hepatocarcinogenesis. To elucidate the biochemical events before the development of HCC, we examined several parameters of oxidative stress and redox homeostasis in a mouse model of HCV-associated HCC. For young mice ages 3-12 months, there was no significant difference in the levels of hydroperoxides of phosphatidylcholine (PCOOH) and phosphatidylethanolamine in liver tissue homogenates between transgenic and nontransgenic control mice. In contrast, the PCOOH level was increased by 180% in old core gene transgenic mice > 16 months old. Concurrently, there was a significant increase in the catalase activity, and there were decreases in the levels of total and reduced glutathione in the same mice. A direct in situ determination by chemiluminescence revealed an increase in hydroperoxide products by 170% even in young transgenic mice, suggesting that hydroperoxides were overproduced but immediately removed by an activated scavenger system in young mice. Electron microscopy revealed lipofuscin granules, secondary lysosomes carrying various cytoplasmic organelles, and disruption of the double membrane structure of mitochondria, and PCR analysis disclosed a deletion in mitochondrial DNA. Interestingly, alcohol caused a marked increase in the PCOOH level in transgenic mice, suggesting synergism between alcohol and HCV in hepatocarcinogenesis. The HCV core protein thus alters the oxidant/antioxidant state in the liver in the absence of inflammation and may thereby contribute to or facilitate, at least in part, the development of HCC in HCV infection.
Cancer Res 2001 Jun 01
PMID:Oxidative stress in the absence of inflammation in a mouse model for hepatitis C virus-associated hepatocarcinogenesis. 1138 61

It is not known whether obesity increases the risk for hepatocellular carcinoma (HCC) simply because it promotes cirrhosis, a general risk factor for HCC, or via some other mechanism that operates independently of cirrhosis. If the latter occurs, then hepatocyte hyperplasia, an early event during the neoplastic process, might begin before liver cirrhosis develops. Genetically obese, leptin-deficient ob/ob mice are models for nonalcoholic fatty liver disease (NAFLD), a type of liver disease that is strongly associated with obesity and type 2 diabetes. Similar to obese, diabetic patients, ob/ob mice have an increased incidence of HCC. However, unlike humans with NAFLD, they rarely, if ever, develop cirrhosis spontaneously. To determine whether the noncirrhotic livers of ob/ob mice with NAFLD exhibit hepatocyte hyperplasia, parameters of proliferation and apoptosis were compared in adult ob/ob mice and their healthy litter mates. Adult ob/ob mice have an increase in liver mass relative to body mass. This hepatomegaly cannot be explained solely by lipid accumulation and is accompanied by significant increases in hepatocyte proliferative activity (as evidenced by increased Erk activation, cell-cycle related gene expression, bromodeoxyuridine incorporation, and hepatic DNA content) with concomitant inhibition of hepatocyte apoptosis (as evidenced by decreased numbers of apoptotic hepatocytes, induction of several antiapoptotic mechanisms, and decreased activation of procaspase 3). Thus, liver hyperplasia is evident at the earliest stage of NAFLD in ob/ob mice, which supports the concept that obesity-related metabolic abnormalities, rather than cirrhosis, initiate the hepatic neoplastic process during obesity.
Cancer Res 2001 Jul 01
PMID:Hepatic hyperplasia in noncirrhotic fatty livers: is obesity-related hepatic steatosis a premalignant condition? 1143 35

Development of hepatocellular carcinomas in rats caused by a choline-deficient, L-amino acid-defined (CDAA) diet, usually associated with fatty liver, fibrosis, cirrhosis and oxidative DNA damage, has been recognized as a useful model of hepatocarcinogenesis caused by endogenous factors. In the present study, in order to further explore involved factors and genes, we established an equivalent model in spontaneous liver tumor-resistant C57BL/6J mice. Six-week-old males and females were continuously fed the CDAA diet and histological liver lesions and oxidative DNA damage due to 8-hydroxydeoxyguanosine (8-OHdG) were examined after 22, 65 and 84 weeks. In male mice, fatty change and fibrosis were evident at 22 weeks, and preneoplastic foci of altered hepatocytes were seen at an incidence of 8/8 (100%) and a multiplicity of 6.6 +/- 4.0 per mouse at 65 weeks. Hepatocellular adenomas and carcinomas developed at incidences of 16/24 (66.7%) and 5/24 (20.8%), and multiplicities of 1.42 +/- 1.32 and 0.29 +/- 0.62, respectively, at 84 weeks. The female mice exhibited resistance to development of these lesions. The CDAA diet also increased 8-OHdG levels in male but not female mice. These results indicate that a CDAA diet causes hepatocellular preneoplastic foci, adenomas and carcinomas associated with fibrosis and oxidative DNA damage in mice, as in rats, providing a hepatocarcinogenesis model caused by endogenous factors in mice.
Jpn J Cancer Res 2002 Feb
PMID:Development of hepatocellular adenomas and carcinomas associated with fibrosis in C57BL/6J male mice given a choline-deficient, L-amino acid-defined diet. 1185 75

C75, a known inhibitor of fatty acid synthase is postulated to cause significant weight loss through decreased hypothalamic neuropeptide Y (NPY) production. Peripherally, C75, an alpha-methylene-gamma-butyrolactone, reduces adipose tissue and fatty liver, despite high levels of malonyl-CoA. To investigate this paradox, we studied the effect of C75 on fatty acid oxidation and energy production in diet-induced obese (DIO) mice and cellular models. Whole-animal calorimetry showed that C75-treated DIO mice had a 50% greater weight loss, and a 32.9% increased production of energy because of fatty acid oxidation, compared with paired-fed controls. Etomoxir, an inhibitor of carnitine O-palmitoyltransferase-1 (CPT-1), reversed the increased energy expenditure in DIO mice by inhibiting fatty acid oxidation. C75 treatment of rodent adipocytes and hepatocytes and human breast cancer cells increased fatty acid oxidation and ATP levels by increasing CPT-1 activity, even in the presence of elevated concentrations of malonyl-CoA. Studies in human cancer cells showed that C75 competed with malonyl-CoA, as measured by CPT-1 activity assays. Thus, C75 acts both centrally to reduce food intake and peripherally to increase fatty acid oxidation, leading to rapid and profound weight loss, loss of adipose mass, and resolution of fatty liver. The pharmacological stimulation of CPT-1 activity is a novel finding. The dual action of the C75 class of compounds as fatty acid synthase inhibitors and CPT-1 agonists has therapeutic implications in the treatment of obesity and type II diabetes.
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PMID:C75 increases peripheral energy utilization and fatty acid oxidation in diet-induced obesity. 1209 27

Diffuse fatty degeneration often occurs after pancreaticoduodenectomy due to altered lipid metabolism and nutritional malabsorption. Focal fatty change of the liver is characterized by a well-demarcated region, and the pathogenesis remains unclear. A 60-year-old woman underwent pancreaticoduodenectomy for bile duct cancer 10 years before. During follow-up, an intrahepatic tumor was detected in the lateral segment in the liver. The differential diagnosis included cholangiocarcinoma and metastatic tumor on images of plain computed tomography, ultrasonography, and magnetic resonance angiography. The patient underwent lateral segmentectomy of the liver. The tumor was a soft yellow mass, and histological examination indicated focal fatty liver. It was thought that the fatty liver was caused by localized low blood supply and dysabsorption of lipoprotein after pancreaticoduodenectomy.
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PMID:Focal fatty liver after pancreaticoduodenectomy: a case report of a rare entity of intrahepatic tumor. 1214 8

Non-alcoholic steatohepatitis (NASH), is a critical link in the chain of metabolic fatty liver disorders that spans steatosis to cryptogenic cirrhosis. It is the hepatic manifestation of the insulin resistance (or metabolic) syndrome, and provides a clue to understanding fibrotic progression of other chronic liver diseases, particularly hepatitis C. Non-alcoholic steatohepatitis is often the first clinical indication of insulin resistance, with its complications of high blood pressure, coronary heart disease and type 2 diabetes. Among those with risk factors, NASH is common: present in at least 20% of obese adults or children with or without type 2 diabetes, and at least 5% of those overweight. With emerging urbanization, increasing affluence and behavioral changes of physical inactivity and high fat/energy-excessive diet, type 2 diabetes has become common in Asia and the western Pacific rim. The rates range from 7-40%, which in countries like Japan represents a 3-20-fold increase (depending on age) over the last 20 years. The increase is associated with central adiposity, insulin resistance, hepatic steatosis and NASH. After cancer, cirrhosis from NASH is now the second most common age-related cause of death in type 2 diabetes. Reversing these trends must become a public health priority; the first awakenings were evident in Taiwan at the time of this meeting. In order to stimulate clinicians to think more about the importance of metabolic liver disease for development of cirrhosis, this review will cover clinical and laboratory features, natural history and an approach to diagnosis and management of NASH. Some emerging concepts on pathogenesis will be mentioned briefly, but the emphasis will be on the potency of lifestyle adjustments (physical activity and diet) to prevent or reverse fatty liver disorders.
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PMID:Non-alcoholic steatohepatitis: what is it, and why is it important in the Asia-Pacific region? 1254 95

Herpes simplex virus thymidine kinase (HSV-tk) converts ganciclovir (GCV) into an active compound, which can be incorporated into DNA molecules and terminate DNA synthesis. Gene transfer of HSV-tk followed by GCV administration has been used with success to treat experimental cancer and this strategy has entered into clinical trials. Although it is thought that the cytotoxic effect occurs mainly in tumoral dividing cells, where mitotic activity favors integration of the genotoxic compound into nuclear DNA, there are concerns of potential damage to normal nondividing cells. In the present work we have explored the mechanisms of HSV-tk/GCV toxicity and in particular whether this therapy may cause lesions of mitochondrial DNA (mtDNA) and mitochondrial dysfunction. We found that the administration of GCV to rats injected with adenovirus encoding HSV-tk induced hepatocellular damage characterized by the presence of apoptotic bodies, ballooning of hepatocytes, and severe hepatic steatosis with mitochondria enlargement and cristae dissolution at the ultrastructural level. Remarkably, Southern blot analysis showed substantial reduction in the amount of mtDNA in the liver. Using radiolabeled GCV we could demonstrate incorporation of this compound into both nuclear and mtDNA in HSV-tk-transduced rat hepatocytic cell line MCA-RH7777 and subsequent alteration of mitochondrial function. Our observations confirm that GCV can damage both nuclear and mtDNA in cells transduced with HSV-tk and that this effect could be responsible for severe mitochondrial dysfunction and toxicity in normal nondividing cells. These data are relevant for the design of clinical trials using adenoviral vectors encoding HSV-tk.
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PMID:Liver failure caused by herpes simplex virus thymidine kinase plus ganciclovir therapy is associated with mitochondrial dysfunction and mitochondrial DNA depletion. 1269 11

There is a great deal of concern regarding the hazard potential of human exposure to toxic substances and carcinogens as well as infectious agents in the environment. For monitoring purposes fish are well established with regard to aquatic pollution. However, for the human environment, mammalian species might be considered more relevant. As the various types of rats are one of the most common animals sharing human habitants they are natural candidates. In the present study, numbers of such wild rats were trapped in the metropolis of Bangkok and country regions of Thailand for comparison of lesions in the liver and lung which might provide indicators of carcinogens or other hazardous agents in the environment. Glutathione S transferase P form positive foci could be detected in livers, comparable to the laboratory rat case, but without any significant link to site of capture. In contrast, fatty liver and inflammation/cirrhosis were significantly more frequent in animals from the metropolis. Parasite infection also tended to be more prevalent, along with leptospirosis. Inflammatory change was similarly found in the lungs but without any variation between the city and countryside groups. These results suggest that wild rats could be employed as monitors of environmental agents of toxicological significance.
Asian Pac J Cancer Prev 2002
PMID:Use of Wild Rodents for Environmental Monitoring - Comparison of Rats in Bangkok and Rural Areas of Thailand. 1271 96

The fatty liver Shionogi (FLS) mouse is an inbred strain that develops spontaneous fatty liver (hepatic steatosis) chronically without obesity. Here, we reported that the mice develop spontaneous hepatocellular tumors with high incidences. The mice with age of over 1 year frequently developed whitish protuberant nodules in the livers, which were histologically diagnosed as hepatocellular adenoma and/or carcinoma (HCC). An incidence of HCC was 12/30 (40%) in males at 15-16 months of age, while in females that was 0/36 at 13-16 months and 4/42 (9.5%) at 20-24 months. Furthermore, histological examinations showed that after 2-4 months of age mononuclear cell infiltration and clusters of foamy cells appear in the fatty liver with elevated serum alanine aminotransferase, suggesting presence of inflammatory responses and liver injury. These observations show that the FLS mice develop hepatocellular tumors following steatohepatitis. The mouse might be a good animal model for investigating liver tumor and non-alcoholic steatohepatitis.
Cancer Lett 2003 Jun 30
PMID:Spontaneous development of hepatocellular carcinomas in the FLS mice with hereditary fatty liver. 1286 Feb 88


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