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)

Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear transcription factor that comprises the primary molecular target for thiazolidinedione (TZD) insulin-sensitizing drugs. Whilst expressed in many tissues in humans, its abundant expression in adipose tissue is believed to be the focal point through which TZDs regulate genes involved in glucose and lipid metabolism and via which these agents ultimately improve the hyperglycemia of type 2 diabetes. However, TZDs exhibit many additional properties, not least an array of effects which suggest a broad attack on the inflammatory process. Thus, TZDs have been shown to reduce plasma levels of the chemokine, monocyte chemotactic protein-1 (MCP-1), the anti-fibrinolytic protein, plasminogen activator inhibitor-1 (PAI-1), the endothelial cell adhesion molecules, e-selectin and inter-cellular adhesion molecule-1 (ICAM-1), the leucocyte-activating molecule, CD40L, and the tissue-remodeling enzyme, matrix metalloproteinase-9 (MMP-9). Further tangible evidence of a reduction by TZDs of systemic inflammation in patients with the classical metabolic syndrome stems from falls in the white blood cell count, P-selectin-positive platelets and in the acute-phase inflammatory proteins, C-reactive protein, serum amyloid A and fibrinogen. At the tissue level, TZDs improve vascular endothelial function, and reduce the rate of progression of intimal-medial thickening of the carotid artery and the microalbuminuria of type 2 diabetes. Further, TZDs have been shown to be efficacious in inflammatory diseases as wide-ranging as psoriasis, ulcerative colitis and non-alcoholic steatohepatitis (NASH). In the case of the latter, a broad spectrum of TZD-related properties is visible. Here, these drugs improve insulin sensitivity for glucose metabolism, reduce hyperinsulinemia, hepatic steatosis, inflammation and fibrosis, and lower the circulating levels of liver transaminases (ALT, AST), alkaline phosphatase and gamma glutamyl transferase. These effects in humans are also well-supported by investigative animal and in vitro studies. The ameliorative effects on liver fibrosis are of particular interest since they suggest that TZDs are able to activate a program of corrective tissue-remodeling. The basis for this action may be partly an ability to inhibit matrix protein secretion by hepatic stellate cells. An analogous action has also been seen in kidney mesangial cells. In conclusion, TZDs are important new drugs, presently indicated for the treatment of type 2 diabetes but with a spectrum of properties which suggests their potential for treating a number of degenerative inflammatory diseases, including NASH. However, full-scale, long-term clinical trials are needed with TZDs to test their potential to treat NASH, not least because of the (hepatotoxic) legacy of the prototype TZD, troglitazone, but also in view of the escalating burden of liver disease which is accompanying the increasing global prevalence of clinical obesity and type 2 diabetes.
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PMID:Thiazolidinediones: Pleiotropic drugs with potent anti-inflammatory properties for tissue protection. 1619 19

The behavior of hepatitis C in states of immunodeficiency is poorly understood and it is still unclear whether the characteristics of hepatitis C virus (HCV) infection in renal transplant patients differ from those observed in immunocompetent subjects. The aim of this study was to compare the biochemical and histologic characteristics of chronic HCV infection between renal transplant and immunocompetent patients. Forty-one HCV-RNA-positive renal transplant patients and 41 immunocompetent controls matched for gender, age at infection and time of infection were included in the study. The groups were compared regarding laboratory and histologic variables. Renal transplant patients showed lower alanine aminotransferase (ALT) levels (p = 0.005) and higher levels of gamma-glutamyltransferase (p = 0.003), alkaline phosphatase (p < 0.001), and direct bilirubin (p < 0.001) when compared with controls. Histologic analysis revealed less intense portal (p < 0.001) and periportal (p = 0.046) inflammatory infiltrate in renal transplant patients but a larger proportion of cases with confluent necrosis (p = 0.043). No difference in the presence of septal fibrosis, hepatic steatosis, bile duct injury and siderosis was observed. However, there was a difference in the presence of lymphoid aggregates, which were less frequent in the renal transplant group (p < 0.001). In conclusion, the characteristics of hepatitis C in renal transplant patients differ from that observed in immunocompetent patients. In renal transplant patients, HCV infection is biochemically characterized by lower ALT levels and higher frequency of cholestasis. Regarding histology, despite lower frequency of lymphoid aggregates and less intense portal/periportal inflammatory infiltrate, a greater lobular damage was observed. The impact of these differences on the progression of fibrosis remains to be established.
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PMID:Hepatitis C virus infection in renal transplant patients: a comparative study with immunocompetent patients. 1631 22

We tested the power of tumor necrosis factor (TNF)-alpha and/or leptin in predicting the degree of liver involvement in children with nonalcoholic fatty liver disease (NAFLD). We measured serum levels of TNF-alpha and leptin and computed NAFLD activity score (NAS) (NAS >or= 5, diagnostic of nonalcoholic steatohepatitis [NASH]) in 72 consecutive biopsy-proven NAFLD cases (training and validation sets, 36 cases each). Univariate analysis evaluated variables significantly associated with a diagnostic NAS. Receiver operating characteristic (ROC) curve analysis assessed the diagnostic value of selected variables in predicting a NAS of 5 or more.TNF-alpha (P < .0001), leptin (P = .001); triglycerides (P = .013), and alkaline phosphatase (P = .046) levels were significantly associated with a NAS of 5 or more. TNF-alpha and leptin levels predicted the risk of NAS of 5 or more. ROC analyses defined cutoff values for TNF-alpha, leptin, and risk score. They identified 90%, 83%, and 83% of the cases, respectively, with a NAS of 5 or more (true-positive cases) from the validation set.TNF-alpha alone or combined with leptin in a simple risk score can accurately predict a NAS of 5 or more. TNF-alpha seems to be a specific laboratory marker of NASH.
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PMID:Correlation of serum TNF-alpha levels and histologic liver injury scores in pediatric nonalcoholic fatty liver disease. 1750 93

This study investigated the effects of rimonabant (SR141716), an antagonist of the cannabinoid receptor type 1 (CB1), on obesity-associated hepatic steatosis and related features of metabolic syndrome: inflammation (elevated plasma levels of tumor necrosis factor alpha [TNFalpha]), dyslipidemia, and reduced plasma levels of adiponectin. We report that oral treatment of obese (fa/fa) rats with rimonabant (30 mg/kg) daily for 8 weeks abolished hepatic steatosis. This treatment reduced hepatomegaly, reduced elevation of plasma levels of enzyme markers of hepatic damage (alanine aminotransferase, gamma glutamyltransferase, and alkaline phosphatase) and decreased the high level of local hepatic TNFalpha currently associated with steatohepatitis. In parallel, treatment of obese (fa/fa) rats with rimonabant reduced the high plasma level of the proinflammatory cytokine TNFalpha and increased the reduced plasma level of the anti-inflammatory hormone adiponectin. Finally, rimonabant treatment also improved dyslipidemia by both decreasing plasma levels of triglycerides, free fatty acids, and total cholesterol and increasing the HDLc/LDLc ratio. All the effects of rimonabant found in this study were not or only slightly observed in pair-fed obese animals, highlighting the additional beneficial effects of treatment with rimonabant compared to diet. These results demonstrate that rimonabant plays a hepatoprotective role and suggest that this CB1 receptor antagonist potentially has clinical applications in the treatment of obesity-associated liver diseases and related features of metabolic syndrome.
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PMID:Rimonabant reduces obesity-associated hepatic steatosis and features of metabolic syndrome in obese Zucker fa/fa rats. 1759 67

Obstructive sleep apnea (OSA) causes chronic intermittent hypoxia (CIH) during sleep. OSA is associated with nonalcoholic steatohepatitis (NASH) in obese individuals and may contribute to progression of nonalcoholic fatty liver disease from steatosis to NASH. The purpose of this study was to examine whether CIH induces inflammatory changes in the liver in mice with diet-induced hepatic steatosis. C57BL/6J mice (n = 8) on a high-fat, high-cholesterol diet were exposed to CIH for 6 mo and were compared with mice on the same diet exposed to intermittent air (control; n = 8). CIH caused liver injury with an increase in serum ALT (461 +/- 58 U/l vs. 103 +/- 16 U/l in the control group; P < 0.01) and AST (637 +/- 37 U/l vs. 175 +/- 13 U/l in the control group; P < 0.001), whereas alkaline phosphatase and total bilirubin levels were unchanged. Histology revealed hepatic steatosis in both groups, with mild accentuation of fat staining in the zone 3 hepatocytes in mice exposed to CIH. Animals exposed to CIH exhibited lobular inflammation and fibrosis in the liver, which were not evident in control mice. CIH caused significant increases in lipid peroxidation in serum and liver tissue; significant increases in hepatic levels of myeloperoxidase and proinflammatory cytokines IL-1beta, IL-6, and CXC chemokine MIP-2; a trend toward an increase in TNF-alpha; and an increase in alpha1(I)-collagen mRNA. We conclude that CIH induces lipid peroxidation and inflammation in the livers of mice on a high-fat, high-cholesterol diet.
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PMID:Chronic intermittent hypoxia causes hepatitis in a mouse model of diet-induced fatty liver. 1800 63

The present study was conducted to evaluate the hepatoprotective effect of Andrographis lineata (Acanthaceae) extracts in carbon tetrachloride-induced liver injury in rats. Male Wistar rats with chronic liver damage, induced by subcutaneous injection of 50% v/v carbon tetrachloride in liquid paraffin at a dose of 3 mL/kg on alternate days for a period of 4 weeks, were treated with methanol and aqueous extracts of A. lineata orally at a dose of 845 mg/kg/day. The biochemical parameters such as serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, serum bilirubin and alkaline phosphatase were estimated to assess the liver function. Histopathological studies of the liver were also carried out to confirm the biochemical changes. Histopathological examinations of liver tissue corroborated well with the biochemical changes. The activities of extracts were comparable to a standard drug. Hepatic steatosis, hydropic degeneration and necrosis were observed in the carbon tetrachloride treated group, while these were completely absent in the standard and extract treated groups. A. lineata extracts exhibited hepatoprotective action against carbon tetrachloride-induced liver injury. The present investigation established pharmacological evidence to support the folklore claim that it is used traditionally as a hepatoprotective agent.
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PMID:Hepatoprotective effect of leaf extracts of Andrographis lineata nees on liver damage caused by carbon tetrachloride in rats. 1770 41

Morinda citrifolia L. (noni) has been used throughout the Pacific, Southeast Asia, Central America, and the Caribbean for a variety of health conditions, including heart and liver ailments. In this study, we examined the hepatoprotective effects of TAHITIAN NONI Juice (TNJ) against CCl(4)-induced chronic liver damage in female Sprague Dawley (SD) rats. Twelve female SD rats were divided into control, placebo and TNJ (6 mL/rat/day) groups. On day 15, animals in the placebo and TNJ groups received 0.25 mL/kg CCl(4) in corn oil once a week for 12 successive weeks. All animals were sacrificed at week 16. Blood and liver were collected for liver function, lipid panel tests, and histological observation. Histopathological examination revealed that liver sections from the TNJ + CCl(4) appeared similar to controls, whereas typical hepatic steatosis was observed in the placebo + CCl(4) group. Serum alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine transaminase (ALT), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) levels were increased in the placebo group compared with the TNJ group. In contrast, high-density lipoprotein (HDL) was increased in the TNJ group and decreased in the placebo group. Thus, TNJ juice appears to protect the liver from chronic exogenous CCl(4) exposures. Such protective mechanisms are supportive evidence for the utility of noni in traditional medicine for liver ailments.
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PMID:Hepatic protection by noni fruit juice against CCl(4)-induced chronic liver damage in female SD rats. 1865 53

This study is to investigate the long-term effects of nanodimension PEG-PLA artificial red blood cells containing hemoglobin and red blood cell enzymes on the liver and spleen after 1/3 blood volume top loading in rats. The experimental rats received one of the following infusions: Nano artificial red blood cells in Ringer lactate, Ringer lactate, stroma-free hemoglobin, polyhemoglobin, and autologous rat whole blood. Blood samples were taken before infusions and on days 1, 7, and 21 after infusions for analysis. Nano artificial red blood cells, polyhemoglobin, Ringer lactate and rat red blood cells did not have any significant adverse effects on alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatine kinase, amylase and creatine kinase. On the other hand, stroma-free hemoglobin induced significant adverse effects on liver as shown by elevation in alanine aminotransferase and aspartate aminotransferase throughout the 21 days. On day 21 after infusions rats were sacrificed and livers and spleens were excised for histological examination. Nano artificial red blood cells, polyhemoglobin, Ringer lactate and rat red blood cells did not cause any abnormalities in the microscopic histology of the livers and spleens. In the stroma-free hemoglobin group the livers showed accumulation of hemoglobin in central veins and sinusoids, and hepatic steatosis. In conclusion, injected nano artificial red blood cells can be efficiently metabolized and removed by the reticuloendothelial system, and do not have any biochemical or histological adverse effects on the livers or the spleens.
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PMID:Long-term effects on the histology and function of livers and spleens in rats after 33% toploading of PEG-PLA-nano artificial red blood cells. 1904 18

The physiological changes in liver function in pregnancy are commonly transient, rarely permanent. Disorders arising in pregnancy, such as pre-eclampsia and eclampsia, acute fatty liver of pregnancy (AFLP), haemolysis, elevated liver enzyme and low platelets (HELLP) syndrome, cholestasis, hyperemesis gravidarum and isolated cases of raised liver enzymes can have serious implications. Proper interpretation of liver function tests (LFTs) at an early stage can lead to timely management and may reduce complications in both mother and fetus. Normal LFTs do not always mean that the liver is normal. A number of pitfalls can be encountered in the interpretation of basic blood LFTs. The commonly used LFTs primarily assess liver injury rather than hepatic function. Abnormal LFTs may indicate that something is wrong with the liver, and they can provide clues to the nature of the problem but this is not always the case. The various biochemical tests, their pathophysiology, and an approach to the interpretation of abnormal LFTs are discussed in this review. Commonly available tests include alanine transaminase, aspartate transaminase, alkaline phosphatase, bile acid, serum bilirubin, serum albumin and prothrombin time.
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PMID:Liver function test and pregnancy. 1933 Jul 14

The purpose of this study was to investigate the level of plasma hepatic enzymes in obese women displaying the metabolically healthy but obese (MHO) phenotype. We studied 104 obese, sedentary, postmenopausal women. Subjects were classified as MHO or at risk based on insulin sensitivity as assessed with the oral glucose tolerance test-derived Matsuda index. Subjects were divided into quartiles according to insulin sensitivity values. Subjects in the upper quartile were categorized as MHO, whereas subjects in the lower 3 quartiles represented at-risk subjects. Outcome measures were hepatic enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase, and gamma-glutamyltransferase [GGT]], high-density lipoprotein cholesterol, triglycerides, triglycerides to high-density lipoprotein cholesterol ratio, apolipoprotein B, fatty liver index, body composition (dual-energy x-ray absorptiometry), and visceral adipose tissue (computed tomography). The MHO individuals had significantly lower concentrations of ALT, AST, and GGT as well as a lower fatty liver index compared with at-risk subjects (P < .05). In addition, lean body mass index and visceral adipose tissue were significantly lower in MHO individuals (P < .05). Moreover, stepwise regression analysis showed that ALT explained 17.9% of the variation in insulin sensitivity in our cohort, which accounted for the greatest source of unique variance. Results of the present study indicate that postmenopausal women displaying the MHO phenotype present favorable levels of ALT, AST, and GGT. Lower concentrations of hepatic enzymes, in particular, lower circulating ALT levels, in MHO individuals may reflect lower hepatic insulin resistance and lower liver fat content; and this could be involved, at least in part, in the protective profile of MHO individuals.
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PMID:Metabolically healthy but obese individuals: relationship with hepatic enzymes. 1970 95


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