benzofurans and Fatty-Liver

Obesity is one of the world's largest health problems, and 3-N-butylphthalide (NBP), a bioactive compound in celery, has been used in dieting and weight management programs. In this study, NBP prevented high-fat-diet-induced weight gain, reduced the food efficiency ratio, altered the blood biochemical profile, and reduced the obesity-related index. NBP reduced adiposity, white fat depots, liver weight, and hepatic steatosis in obese mice. NBP ameliorated the diabetic state by decreasing glucose levels and improving glucose and insulin tolerance. NBP increased uncoupling protein-1 expression in white adipose tissue and upregulated thermogenesis by enhancing mitochondrial respiration. NBP inhibited white adipocyte development by prohibiting lipid accumulation in human adipose-derived stem cells. NBP increased free fatty acid uptake and the oxygen consumption rate in beige adipocytes. Our results suggest that NBP could be used as functional natural supplement against obesity and its associated disorders.

Topics: Adipocytes; Adipose Tissue, White; Adiposity; Animals; Benzofurans; Blood Glucose; Cells, Cultured; Diet, High-Fat; Fatty Liver; Humans; Lipid Metabolism; Lipids; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Protective Agents; Thermogenesis

Environmental exposure to 2,3,7,8-tetrachlorodibenzofuran (TCDF), one of typical persistent organic pollutants (POPs) produced from municipal waste combustion, exerts toxic effects on human healthy. In the current study, we mainly used targeted metabolomics combined with untargeted

Topics: Animals; Benzofurans; Fatty Liver; Humans; Liver; Male; Metabolomics; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease

Topics: Animals; Benzofurans; Endoplasmic Reticulum Stress; Fatty Liver; Fluorescent Dyes; HeLa Cells; Humans; Lipid Droplets; Lipidoses; Mice; Microscopy, Fluorescence; Photons

Allantoin is known as the agonist of imidazoline receptor, especially the I₂ subtype. Effect of allantoin on imidazoline I₁ receptor (I₁R) relating to reduction of blood pressure and its merit in steatosis are still obscure. Also, farnesoid X receptor (FXR) plays an important role in lipid homeostasis related to I₁R activation. Thus, we administered allantoin into high fat diet (HFD)-fed mice showing hypertriglyceridemia and hypercholesterolemia. Allantoin significantly improved hyperlipidemia in HFD mice after 4 weeks of administration. Pretreatment with efaroxan, at a dose sufficient to inhibit I₁R activation, attenuated the action of allantoin. In addition, in cultured HepG2 cells, allantoin increased the expression of farnesoid X receptor (FXR). The allantoin-induced FXR expression was blocked by efaroxan. Similar changes were observed in the expressions of FXR-targeted genes. Otherwise, allantoin also lowered systolic blood pressure (SBP) in HFD mice that can be blocked by efaroxan. Taken together, allantoin has an ability to activate I₁R for improvement of metabolic disorders.

Topics: Allantoin; Animals; Anticholesteremic Agents; Antihypertensive Agents; Benzofurans; Diet, High-Fat; Fatty Liver; Hep G2 Cells; Humans; Hypercholesterolemia; Hypertriglyceridemia; Hypolipidemic Agents; Imidazoles; Imidazoline Receptors; Liver; Male; Mice; Mice, Inbred C57BL; Receptors, Cytoplasmic and Nuclear; Receptors, LDL; Up-Regulation

Cirrhotic portal hypertension is characterized by increased hepatic oxidative stress, AA (arachidonic acid)-derived TXA(2) (thromboxane A(2)) release and exaggerated hepatic response to the α-adrenergic agonist MTX (methoxamine). Besides promoting hepatic fibrosis, the role of hyperleptinaemia in the modulation of vascular response in NASH (non-alcoholic steatohepatitis) rat livers remains unknown. The aim of the present study was to explore the possible links between hyperleptinaemia and the disarrangement in the hepatic microcirculation. NASH-cirrhosis with hyperleptinaemia was induced in lean rats by feeding with an HF/MCD (high-fat/methionine-choline-deficient) diet. Portal haemodynamics, various substances, protein and mRNA expression and PUFA (polyunsaturated fatty acid) composition were measured. Finally, the effects of leptin pre-infusion on TXA(2) release and concentration-PPP (portal perfusion pressure) curves in response to MTX were evaluated by simultaneously pre-treatment with the Kupffer cell inactivators GdCl(3) (gadolinium chloride) or EC (encapsulated clodronate), the TXS (TXA(2) synthase) inhibitor furegrelate, the TP receptor (TXA(2) receptor) antagonist SQ29548 and the dual TXS/TP receptor antagonist BM567. In HF/MCD+leptin-lean rats, cirrhosis-induced PPP and MTX hyper-responsiveness were associated with increased hepatic TXA(2) production, TBARS (thiobarbituric acid-reacting substances) levels and the AA (arachidonic acid)/n-3 PUFA ratio, and up-regulation of hepatic leptin, FAS (fatty acid synthase), NADPH oxidase subunits, TXS, TP receptor, TGFβ(1) (transforming growth factor β(1)) proteins and mRNAs. Pre-infusion of leptin significantly enhanced MTX-stimulated PPP elevation and TXA(2) release, which were attenuated by GdCl(3) and EC pre-treatment. Concomitantly pre-incubation with BM567, but not furegrelate or SQ29548, significantly abolished the leptin-enhanced MTX-stimulated increase in PPP in NASH-cirrhotic rats. Hyperleptinaemia plays an important role in hyper-responsiveness to MTX in NASH-cirrhotic rat livers with portal hypertension. The leptin-enhanced MTX-stimulated increase in PPP is mediated by increased oxidative stress and Kupffer-cell-activated AA-derived TXA(2) release in NASH-cirrhotic rats.

Topics: Analysis of Variance; Animals; Arachidonic Acid; Benzofurans; Choline; Clodronic Acid; Diet, High-Fat; DNA Primers; Fatty Acids, Unsaturated; Fatty Liver; Gadolinium; Hemodynamics; Hypertension, Portal; Insulin Resistance; Kupffer Cells; Leptin; Methionine; Methoxamine; Microcirculation; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Rats; Receptors, Thromboxane A2, Prostaglandin H2; RNA, Messenger; Sulfonylurea Compounds; Thiobarbituric Acid Reactive Substances; Thromboxane A2

The relevance of oxidative stress in mice fed a choline-deficient diet (CDD) was investigated in relation to the oxidative stress marker, hydroxyoctadecadienoic acid (HODE) in comparison with F2-isoprostanes. Further, the protective effects of antioxidants against oxidative damage were assessed by using HODE.. We recently proposed total HODE as a biomarker for oxidative stress in vivo. Biological samples such as plasma, urine, and tissues were first reduced and then saponified to convert various oxidation products of linoleates to HODE. In the present study, this method was applied to measure oxidative damage in mice induced by CDD for 1 mo.. CDD, when compared with choline-controlled diet (CCD), increased liver weight and fatty acid accumulation but the increase in body weight was less significant. Remarkable increases in HODE and 8-iso-prostaglandin F(2alpha) in liver and plasma were observed when mice were fed with the CDD for 1 mo compared with the CCD. The HODE level was about two to three orders higher than the F2-isoprostane level. This increase was decreased to the level of the CCD when alpha-tocopherol or 2,3-dihydro-5-hydroxy-4,6-di-tert-butyl-2,2-dipentylbenzofuran, a potent synthetic antioxidant, was mixed with the CDD. The stereoisomer ratio of HODE (9-and-13 (Z,E)-HODE/9-and-13 (E,E)-HODE) was decreased by CDD compared with CCD, which was spared by the addition of alpha-tocopherol and 2,3-dihydro-5-hydroxy-4,6-di-tert-butyl-2,2-dipentylbenzofuran. However, the increase in plasma glutamic-pyruvic transaminase and fatty acids in liver induced by the CDD was not recovered by any antioxidant.. This study clearly demonstrated that oxidative stress was involved in fatty liver formation induced by the CDD and that HODE was a good biomarker for an oxidative stress in vivo.

Topics: Animals; Antioxidants; Benzofurans; Biomarkers; Choline; Choline Deficiency; Chromatography, High Pressure Liquid; Dinoprost; Fatty Acids, Unsaturated; Fatty Liver; Lipid Peroxidation; Male; Mice; Mice, Inbred C57BL; Organ Size; Oxidation-Reduction; Oxidative Stress; Random Allocation; Specific Pathogen-Free Organisms

Five patients had amiodarone hepatotoxicity detected on routine biochemical monitoring. Symptoms attributable to hepatotoxicity were minimal or absent; reversible hepatomegaly was seen in two patients, whereas three patients had signs of nonhepatic amiodarone toxicity before or with hepatotoxicity. Serum aminotransferase levels were elevated in all patients and alkaline phosphatase levels in four; no patient had hyperbilirubinemia or prolongation of the prothrombin time. Light microscopy showed steatosis, cellular degeneration, and cellular necrosis in the biopsy samples of four patients, whereas the fifth patient's sample had a granulomatous injury pattern. Electron microscopic study of liver tissue done in two patients showed phospholipid-laden lysosomal lamellar bodies. These findings suggest that both toxic and hypersensitivity liver injury can occur in response to amiodarone. The presence of phospholipid-laden lysosomal lamellar bodies may help differentiate amiodarone hepatotoxicity from alcoholic liver disease or other causes of hepatic steatosis.

Topics: Aged; Alanine Transaminase; Alkaline Phosphatase; Amiodarone; Aspartate Aminotransferases; Benzofurans; Chemical and Drug Induced Liver Injury; Fatty Liver; Female; Hepatomegaly; Humans; Liver; Liver Diseases; Male; Middle Aged

Topics: Amiodarone; Animals; Benzofurans; Fatty Liver; Heart; Liver; Lung; Male; Myocardium; Rats; Rats, Inbred Strains

Topics: Adult; Benzofurans; Blood Glucose; Blood Sedimentation; Colchicine; Creatinine; Diabetes Mellitus; Electrocardiography; Fatty Liver; Female; Gout; Humans; Hyperlipidemias; Hypertension; Lipids; Liver Function Tests; Male; Middle Aged; Uric Acid