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Hepatic Levels (hepatic + level)

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Medical Sciences	90%

Selected Abstracts

Mild zinc deficiency and dietary phytic acid accelerates the development of fulminant hepatitis in LEC rats

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2 2007
Akiko Saito
Abstract Background and Aim:, Restriction of copper intake delays hepatic copper accumulation in Long,Evans Cinnamon (LEC) rats, which are animal models of Wilson's disease. Involvement of zinc is suggested to develop hepatitis in the disease; however, this has not been clarified. The aims of this study were to investigate the effects of mild zinc deficiency on the development of hepatitis and to determine the relationship between the absorption and hepatic levels of copper, zinc and iron. Methods:, Male LEC and F344 (wild type atp7b) rats were fed a low zinc, phytate-containing or control diet. The onset of hepatitis (Experiment 1), and absorptive rates of copper, zinc and iron and hepatitis indices in 4 weeks (Experiment 2) were observed. Results:, The onset of fulminant hepatitis in LEC rats was much earlier in the low zinc and phytate groups (mean 94.6 ± 2.74 days and 82.8 ± 3.56 days old, respectively) than in the control group (136 ± 2.11 days old) with worse hepatitis indices. Hepatic copper levels were much higher in LEC rats than F344 rats, but were not largely different among the diet groups without prominent changes in copper absorption. Hepatic levels and intestinal absorption of zinc and iron were lower in the phytate group than in the control group. Conclusion:, Mild zinc deficiencies caused by a low zinc or phytate-containing diet accelerate the onset of hepatitis in LEC rats without increasing copper absorption, and zinc and iron metabolism may be involved in the earlier onset of jaundice of LEC rats. [source]

Vitamins A1 and A2 in hepatic tissue and subcellular fractions in mink feeding on fish-based diets and exposed to Aroclor 1242

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2002
Anne Käkelä
Abstract Two-month-old female mink were fed diets based on either Baltic herring (Clupea harengus membras) or freshwater smelt (Osmerus eperlanus) for 21 weeks. A portion of the smelt-fed mink were exposed orally to polychlorinated biphenyls (PCBs), Aroclor 1242 (1 mg/d). Retinol (vitamin A1), 3,4-didehydroretinol (vitamin A2), and their different fatty acyl esters were studied in hepatic tissue, microsomes, and cytosol by argentated reversed-phase high-performance liquid chromatography. As a result of Aroclor exposure, concentrations of the fatty acyl esters of vitamins A1 and A2 were about one-tenth and those of unesterified A2 one-fourth those of the control levels. In the fatty acyl esters, percentages of stearates (A1 -18:0 and A2 -18:0) increased at the expense of the other fatty acyl esters. The Aroclor exposure decreased concentrations of alcoholic and esterified forms of the A2 analog more than those of the corresponding A1 analog. In microsomes, Aroclor decreased the alcoholic and esterified vitamin analogs to the same extent (to 9,17%). In the cytosol compared to the control, the concentrations of the vitamin esters fell below 10%, but the alcoholic analogs remained at 30 to 40%. Despite equal dietary supply, in mink fed on Baltic herring, the hepatic levels of vitamin A1 were only about one-third of the values found in the smelt-fed mink. The organochlorines also altered hepatic lipid composition and impaired breeding and kit growth. In the kits of the females fed on Baltic herring, blood hemoglobin was decreased. [source]

Effect of transition metal ions (cobalt and nickel chlorides) on intestinal iron absorption

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2004
G. O. Latunde-Dada
Abstract Background, Haem biosynthesis may regulate intestinal iron absorption through changes in cellular levels of ,-aminolaevulinic acid (ALA), haem and perhaps other intermediates. CoCl2 and NiCl2 are activators of haem oxygenase, the rate-limiting enzyme in haem catabolism. Co2+ and Ni2+ may also regulate and increase iron absorption through a mechanism that simulates hypoxic conditions in the tissues. Design, We assayed intestinal iron absorption in mice dosed with CoCl2 or NiCl2. The effects of these metal ions on splenic and hepatic levels of ALA synthase and dehydratase as well as urinary levels of ALA and phosphobilinogen were also assayed. Results, While Co2+ enhanced iron absorption when administered to mice at doses of 65, 125 and 250 µmoles kg,1 body weight, Ni2+ was effective only at the highest dose. Ni2+ but not Co2+ at the highest dose reduced urinary ALA in the treated mice. Both metals ions increased splenic expression of haem oxygenase 1 and iron regulated protein 1, proteins involved, respectively, in haem degradation and iron efflux. Co2+ induced erythropoietin expression. Conclusions, The data suggest that while the effect of Ni2+ on iron absorption could be explained by effects on ALA, the effect of Co2+ may not be explained simply by changes in haem metabolism; therefore, effects mediated by alterations of specific haemoproteins by mechanisms that simulate tissue hypoxia could be important. [source]

Interplay of hepatic and myeloid signal transducer and activator of transcription 3 in facilitating liver regeneration via tempering innate immunity,

HEPATOLOGY, Issue 4 2010
Hua Wang
Liver regeneration triggered by two-thirds partial hepatectomy is accompanied by elevated hepatic levels of endotoxin, which contributes to the regenerative process, but liver inflammation and apoptosis remain paradoxically limited. Here, we show that signal transducer and activator of transcription 3 (STAT3), an important anti-inflammatory signal, is activated in myeloid cells after partial hepatectomy and its conditional deletion results in an enhanced inflammatory response. Surprisingly, this is accompanied by an improved rather than impaired regenerative response with increased hepatic STAT3 activation, which may contribute to the enhanced liver regeneration. Indeed, conditional deletion of STAT3 in both hepatocytes and myeloid cells results in elevated activation of STAT1 and apoptosis of hepatocytes, and a dramatic reduction in survival after partial hepatectomy, whereas additional global deletion of STAT1 protects against these effects. Conclusion: An interplay of myeloid and hepatic STAT3 signaling is essential to prevent liver failure during liver regeneration through tempering a strong innate inflammatory response mediated by STAT1 signaling. (HEPATOLOGY 2010.) [source]

Earlier expression of the transcription factor HFH-11B diminishes induction of p21CIP1/WAF1 levels and accelerates mouse hepatocyte entry into S-phase following carbon tetrachloride liver injury

HEPATOLOGY, Issue 6 2001
Xinhe Wang
Partial hepatectomy (PH) or toxic liver injury induces the proliferation of terminally differentiated hepatic cells to regenerate the original size of the adult liver. Previous PH liver regeneration studies showed that premature transgenic expression of the Forkhead Box M1b (FoxM1b, HFH-11B) transcription factor accelerated hepatocyte entry into DNA replication (S-phase). In this study, we used carbon tetrachloride (CCl4) liver injury to induce a different type of mouse liver regeneration and show that premature hepatic HFH-11B levels also accelerate the onset of hepatocyte S-phase in this injury model. Unlike PH liver regeneration, earlier hepatocyte proliferation after CCl4 liver injury is correlated with diminished transgenic hepatic levels of p21CIP1/WAF1 at the G1/S transition of the cell cycle. Differential hybridization of cDNA arrays and RNase protection studies determined that CCl4 regenerating liver of transgenic mice displayed early stimulated expression of the S-phase promoting cyclin D1 and cyclin E and sustained levels of Cdc25a phosphatase genes. Compared with previous PH liver regeneration studies, our data suggest that premature expression of HFH-11B activates distinct S-phase promotion pathways in the CCl4 liver injury model. Although proliferating transgenic hepatocytes induced by either PH or CCl4 liver injury displayed early expression of identical M-phase cyclin genes (cyclin B1, B2, A2, and F), only CCl4 regenerating transgenic liver exhibited earlier expression of the M-phase promoting Cdc25b. These studies suggest that CCl4 injury of transgenic liver not only uses the same mechanisms as PH to mediate accelerated hepatocyte entry into mitosis, but also promotes M-phase entry by stimulating Cdc25b expression. [source]

Estrogen is involved in early alcohol-induced liver injury in a rat enteral feeding model

HEPATOLOGY, Issue 1 2000
Ming Yin
The aim of this study was to investigate whether reduction in blood estrogen by removal of the ovaries would decrease the sensitivity of female rats to early alcohol-induced liver injury using an enteral ethanol feeding model, and if so, whether estrogen replacement would compensate. Livers from ovariectomized rats with or without estrogen replacement after 4 weeks of continuous ethanol exposure were compared with nonovariectomized rats in the presence or absence of ethanol. Ethanol increased serum alanine transaminase (ALT) levels from 30 ± 6 to 64 ± 7 U/L. This effect was blocked by ovariectomy (31 ± 7) and totally reversed by estrogen replacement (110 ± 23). Ethanol increased liver weight and fat accumulation, an effect that was minimized by ovariectomy and reversed partially by estrogen replacement. Infiltrating leukocytes were increased 6.7-fold by ethanol, an effect that was blunted significantly by ovariectomy and reversed by estrogen replacement. Likewise, a similar pattern of changes was observed in the number of necrotic hepatocytes. Blood endotoxin and hepatic levels of CD14 messenger RNA (mRNA) and protein were increased by ethanol. This effect was blocked in ovariectomized rats and elevated by estrogen replacement. Moreover, Kupffer cells isolated from ethanol-treated rats with estrogen replacement produced more tumor necrosis factor , (TNF-,) than those from control and ovariectomized rats. It is concluded, therefore, that the sensitivity of rat liver to alcohol-induced injury is directly related to estrogen, which increases endotoxin in the blood and CD14 expression in the liver, leading to increased TNF-, production. [source]

Mild zinc deficiency and dietary phytic acid accelerates the development of fulminant hepatitis in LEC rats

Anti-Inflammatory and Anti-Apoptotic Roles of Endothelial Cell STAT3 in Alcoholic Liver Injury

ALCOHOLISM, Issue 4 2010
Andrew M. Miller
Background:, It is generally believed that the hepatoprotective effect of interleukin-6 (IL-6) is mediated via activation of signal transducer and activator of transcription 3 (STAT3) in hepatocytes. IL-6-deficient mice are more susceptible to alcohol-induced hepatocyte apoptosis and steatosis and elevation of serum alanine transaminase (ALT); however, whereas hepatocyte-specific STAT3 knockout mice are more susceptible to alcohol-induced hepatic steatosis, they have similar hepatocyte apoptosis and serum ALT after alcohol feeding compared with wild-type mice. This suggests that the hepatoprotective effect of IL-6 in alcoholic liver injury may be mediated via activation of STAT3-independent signals in hepatocytes, activation of STAT3 in nonparenchymal cells, or both. We have previously shown that IL-6 also activates STAT3 in sinusoidal endothelial cells (SECs). Thus, the purpose of this study was to investigate whether STAT3 in endothelial cells also plays a protective role in alcoholic liver injury. Methods:, Wild-type and endothelial cell-specific STAT3 knockout (STAT3E,/,) mice were pair-fed and fed ethanol containing diet for 4 weeks. Liver injury and inflammation were determined. Results:, Feeding mice with ethanol-containing diet for 4 weeks induced greater hepatic injury (elevation of serum ALT) and liver weight in STAT3E,/, mice than wild-type control groups. In addition, ethanol-fed STAT3E,/, mice displayed greater hepatic inflammation and substantially elevated serum and hepatic levels of IL-6 and TNF-, compared with wild-type mice. Furthermore, ethanol-fed STAT3E,/, mice displayed a greater abundance of apoptotic SECs and higher levels of serum hyaluronic acid than wild-type controls. Conclusions:, These data suggest that endothelial cell STAT3 plays important dual functions of attenuating hepatic inflammation and SEC death during alcoholic liver injury. [source]

Molecular Mechanisms of Alcoholic Fatty Liver

ALCOHOLISM, Issue 2 2009
Vishnudutt Purohit
Alcoholic fatty liver is a potentially pathologic condition which can progress to steatohepatitis, fibrosis, and cirrhosis if alcohol consumption is continued. Alcohol exposure may induce fatty liver by increasing NADH/NAD+ ratio, increasing sterol regulatory element-binding protein-1 (SREBP-1) activity, decreasing peroxisome proliferator-activated receptor-, (PPAR-,) activity, and increasing complement C3 hepatic levels. Alcohol may increase SREBP-1 activity by decreasing the activities of AMP-activated protein kinase and sirtuin-1. Tumor necrosis factor-, (TNF-,) produced in response to alcohol exposure may cause fatty liver by up-regulating SREBP-1 activity, whereas betaine and pioglitazone may attenuate fatty liver by down-regulating SREBP-1 activity. PPAR-, agonists have potentials to attenuate alcoholic fatty liver. Adiponectin and interleukin-6 may attenuate alcoholic fatty liver by up-regulating PPAR-, and insulin signaling pathways while down-regulating SREBP-1 activity and suppressing TNF-, production. Recent studies show that paracrine activation of hepatic cannabinoid receptor 1 by hepatic stellate cell-derived endocannabinoids also contributes to the development of alcoholic fatty liver. Furthermore, oxidative modifications and inactivation of the enzymes involved in the mitochondrial and/or peroxisomal ,-oxidation of fatty acids could contribute to fat accumulation in the liver. [source]

The cytoprotective effects of addition of activated protein C into preservation solution on small-for-size grafts in rats

LIVER TRANSPLANTATION, Issue 1 2010
Naohisa Kuriyama
Small-for-size liver grafts are a serious obstacle for partial orthotopic liver transplantation. Activated protein C (APC), a potent anticoagulant serine protease, is known to have cell-protective properties due to its anti-inflammatory and antiapoptotic activities. This study was designed to examine the cytoprotective effects of a preservation solution containing APC on small-for-size liver grafts, with special attention paid to ischemia-reperfusion injury and shear stress in rats. APC exerted cytoprotective effects, as evidenced by (1) increased 7-day graft survival; (2) decreased initial portal pressure and improved hepatic microcirculation; (3) decreased levels of aminotransferase and improved histological features of hepatic ischemia-reperfusion injury; (4) suppressed infiltration of neutrophils and monocytes/macrophages; (5) reduced hepatic expression of tumor necrosis factor , and interleukin 6; (6) decreased serum levels of hyaluronic acid, which indicated attenuation of sinusoidal endothelial cell injury; (7) increased hepatic levels of nitric oxide via up-regulated hepatic endothelial nitric oxide synthesis expression together with down-regulated hepatic inducible nitric oxide synthase expression; (8) decreased hepatic levels of endothelin 1; and (9) reduced hepatocellular apoptosis by down-regulated caspase-8 and caspase-3 activities. These results suggest that a preservation solution containing APC is a potential novel and safe product for small-for-size liver transplantation, alleviating graft injury via anti-inflammatory and antiapoptotic effects and vasorelaxing conditions. Liver Transpl 16:1,11, 2010. © 2009 AASLD. [source]

Further studies on the hepatoprotective effects of Anoectochilus formosanus,

PHYTOTHERAPY RESEARCH, Issue 3 2008
Hsun-Lang Fang
Abstract The purpose of this study was to investigate the hepatoprotective effects of Anoectochilus formosanus effective fraction (AFEF) on chronic liver damage induced by carbon tetrachloride (CCl4) in mice. CCl4 (5%; 0.1 mL/10 g body weight) was given twice a week for 9 weeks, and mice received AFEF throughout the whole experimental period. Plasma GPT, hepatic levels of hydroxyproline and malondialdehyde were significantly lower in mice treated with AFEF compared with those treated with CCl4 only. Liver pathology in the AFEF-treated mice was also improved. RT-PCR analysis showed that AFEF treatment increased the expression of methionine adenosyltransferase 1A and decreased the expression of collagen(,1)(I) and transforming growth factor-,1. These results clearly demonstrated that AFEF reduced the hepatic damage induced by CCl4 in mice. Copyright © 2007 John Wiley & Sons, Ltd. [source]