Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Minocycline has anti-inflammatory and antiapoptotic effects on cartilage, neurons and periodontal tissues, and both properties are central to the pharmaceutical treatment of liver diseases. We investigated the effects of minocycline on fulminant hepatitis in C57BL/6J mice induced by lethal challenge of the activating anti-Fas antibody, Jo2. 2. Intraperitoneal injection of Jo2 (0.6 microg g(-1)) to mice resulted in fulminant hepatitis, as evidenced by increase of serum alanine/aspartate transaminase activities and histopathological alterations in liver sections, as well as animal death. Nevertheless, mice pretreated with three doses of minocycline (5 mg kg(-1)) resisted this lethal effect significantly. Minocycline treatment improved the survival kinetics, although to a lesser extent, when mice were challenged simultaneously with Jo2 or even treated 30 min after the lethal challenge. 3. Jo2-induced activation of caspase-3 or -9 in liver tissues was inhibited by minocycline pretreatment, and yet the direct addition of minocycline to liver extracts from Jo2-challenged mice failed to block caspase activation in vitro. Moreover, minocycline efficiently suppressed the release of cytochrome c from mitochondria of the liver tissues from Jo2-challenged mice. In contrast, caspase-8 activation and Bid truncation triggered by Jo2 were not diminished by minocycline pretreatment in mouse livers. 4. Our results suggest that easing of Fas-triggered fulminant hepatitis by minocycline may involve a mitochondrial apoptotic pathway, probably through preventing cytochrome c release and thereby blocking downstream caspase activation.
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PMID:Effects of minocycline on Fas-mediated fulminant hepatitis in mice. 1566 64

The normalization of plasma alanine aminotransferase (ALT) has been proved to be a strategy for preventing the development of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-infection. Glycyrrhizin, a plant medicine, normalizes plasma ALT and prevents HCC. However, glycyrrhizin is administered intravenously and thereby chemical which is effective on oral administration is required. Coumarin compounds are active components of herbs used for the treatment of various diseases. The ability of coumarin compounds to lower plasma ALT were examined using mice concanavalin A-induced hepatitis and mice anti-Fas antibody-induced hepatitis. Furanocoumarins pd-Ia, pd-II and pd-III lower plasma ALT, but they are large molecules that are hardly absorbed on oral administration. Furocoumarin effectively lowers plasma ALT, but the safety range between the effective and toxic dosages is narrow. In contrast, osthole, a simple coumarin, causes strong reduction of plasma ALT and also inhibits caspase-3 activation. Furthermore, this chemical is quite safe upon large dose administration. In the structure of osthole, the methoxy group at position-7 and the 3-methyl-2-butenyl group at position-8 were elucidated to be essential for the beneficial effect of this chemical. We conclude that osthole will become a leading chemical for synthesizing a compound which prevents HCC on oral administration.
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PMID:Chemical aspects of coumarin compounds for the prevention of hepatocellular carcinomas. 1572 Feb 60

Nan-Chai-Hu, the root of Bupleurum scorzonerifolium, is a traditional Chinese herb used in treatment of liver diseases such as hepatitis and cirrhosis. We recently reported that the acetone extract of B. scorzonerifolium (BS-AE) could inhibit proliferation and induce apoptosis in A549 human lung cancer cells. We further examined its anti-proliferative mechanisms and in vivo anticancer effect. Our results showed that BS-AE had the ability to cause cell cycle arrest in G2/M phase, inducing tubulin polymerization, and activating caspase-3 and -9 in A549 cells. BS-AE-induced apoptosis could be blocked by the broad caspase inhibitor z-VAD-fmk in majority. The result of in vivo study showed that BS-AE could suppress growth in A549 subcutaneous xenograft tumors. These results indicate that BS-AE exerts antiproliferative effects on A549 cells in vitro and in vivo, and prompted us to further evaluate and elucidate the chemical composition profile of BS-AE.
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PMID:Anti-proliferative activity of Bupleurum scrozonerifolium in A549 human lung cancer cells in vitro and in vivo. 1586 67

NKT cells expressing phenotypic markers of both T and NK cells seem to be pivotal in murine models of immune-mediated liver injury, e.g., in Con A-induced hepatitis. Also alpha-galactosylceramide (alpha-GalCer), a specific ligand for invariant Valpha14 NKT cells, induces hepatic injury. To improve the comprehension of NKT-cell mediated liver injury, we investigated concomitants and prerequisites of alpha-GalCer-induced hepatitis in mice. Liver injury induced by alpha-GalCer injection into C57BL/6 mice was accompanied by intrahepatic caspase-3 activity but appeared independent thereof. alpha-GalCer injection also induces pronounced cytokine responses, including TNF-alpha, IFN-gamma, IL-2, IL-4, and IL-6. We provide a detailed time course for the expression of these cytokines, both in liver and plasma. Cytokine neutralization revealed that, unlike Con A-induced hepatitis, IFN-gamma is not only dispensable for alpha-GalCer-induced hepatotoxicity but even appears to exert protective effects. In contrast, TNF-alpha was clearly identified as an important mediator for hepatic injury in this model that increased Fas ligand expression on NKT cells. Whereas intrahepatic Kupffer cells are known as a pivotal source for TNF-alpha in Con A-induced hepatitis, they were nonessential for alpha-GalCer-mediated hepatotoxicity. In alpha-GalCer-treated mice, TNF-alpha was produced by intrahepatic lymphocytes, in particular NKT cells. BALB/c mice were significantly less susceptible to alpha-GalCer-induced liver injury than C57BL/6 mice, in particular upon pretreatment with d-galactosamine, a hepatocyte-specific sensitizer to TNF-alpha-mediated injury. Finally, we demonstrate resemblance of murine alpha-GalCer-induced hepatitis to human autoimmune-like liver disorders. The particular features of this model compared with other immune-mediated hepatitis models may enhance comprehension of basic mechanisms in the etiopathogenesis of NKT cell-comprising liver disorders.
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PMID:Alpha-galactosylceramide-induced liver injury in mice is mediated by TNF-alpha but independent of Kupffer cells. 1603 92

Wilson's disease (WD) is an inherited disorder, characterized by selective copper deposition in liver and brain, chronic hepatitis and extra-pyramidal signs. In this study, we investigated changes of biochemical markers of oxidative stress and apoptosis in liver, striatum and cerebral cortex homogenates from Long-Evans Cinnamon (LEC) rats, a mutant strain isolated from Long Evans (LE) rats, in whom spontaneous hepatitis develops shortly after birth. LEC and control (LE) rats at 11 and 14 weeks of age were used. We determined tissue levels of glutathione (GSH/GSSG ratio), lipid peroxides, protein-thiols (P-SH), nitric oxide metabolites, activities of caspase-3 and total superoxide-dismutase (SOD), striatal levels of monoamines and serum levels of hepatic amino-transferases. We observed a decrease of protein-thiols, GSH/GSSG ratio and nitrogen species associated to increased lipid peroxidation in the liver and striatum - but not in the cerebral cortex - of LEC rats, accompanied by dramatic increase in serum amino-transferases and decrease of striatal catecholamines. Conversely, SOD and caspase-3 activity increased consistently only in the cortex of LEC rats. Hence, we assume that enhanced oxidative stress may play a central role in the cell degeneration in WD, at the main sites of copper deposition, with discrete pro-apoptotic conditions developing in distal areas.
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PMID:Oxidative stress and pro-apoptotic conditions in a rodent model of Wilson's disease. 1608 Dec 51

It is well-documented that alcohol drinking together with hepatitis viral infection accelerates liver injury; however the underlying mechanisms remain unknown. In this paper, we demonstrated that primary hepatocytes from transgenic mice overexpressing hepatitis B virus X protein (HBX) were more susceptible to ethanol- and TNF-alpha-induced apoptotic killing. Compared to normal control mouse hepatocytes, ethanol and/or TNF-alpha treatment led to a significant increase in reactive oxygen species, mitochondrial permeability transition, cytochrome C release, caspase-3 activity, and poly (ADP-ribose) polymerase degradation in hepatocytes from HBX transgenic mice. Blocking caspase-3 activity antagonized ethanol- and TNF-alpha-induced apoptosis in primary hepatocytes from HBX transgenic mice. Taken together, our findings suggest that HBX sensitizes primary mouse hepatocytes to ethanol- and TNF-alpha-induced apoptosis by a caspase-3-dependent mechanism, which may partly explain the synergistic effects of alcohol consumption and hepatitis B virus infection on liver injury.
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PMID:Hepatitis B virus X protein sensitizes primary mouse hepatocytes to ethanol- and TNF-alpha-induced apoptosis by a caspase-3-dependent mechanism. 1621 10

Scutellaria barbata has long been used as a Chinese medicine for the treatment of liver diseases such as hepatitis and hepatocellular carcinoma. In the present study, a bioassay-guided method was used to isolate the most active components from Scutellaria barbata. The anti-proliferative effects on human hepatoma HepG2 and Hep3B cells of each fraction at every stage of the purification were monitored. An active component, which is 97% pure by high performance liquid chromatographic analysis, was isolated. Based on nuclear magnetic resonance (NMR) and mass spectrophotometric (MS) analysis, this active component was identified to be pheophorbide a (C35H36N4O5). Mechanistic studies showed that pheophorbide a induced apoptosis in Hep3B cells, a viral-induced hepatoma cell line. However, it was found to be non-toxic in normal human liver cells WRL-68. DNA fragmentation, sub-G1 cell cycle arrest, as well as suppression of the anti-apoptotic protein Bcl-2, release of cytochrome c to the cytosol, and activation of pro-caspase 3 and pro-caspase 9 were observed when Hep3B cells were treated with 40 microg/mL (i. e., 67.5 microM) pheophorbide a for 48 hours. In conclusion, this is the first report describing the isolation of pheophorbide a from Scutellaria barbata using a bioassay-guided isolation method. The anti-proliferative activity and possible mechanisms of action of pheophorbide a on hepatoma Hep3B cells are also discussed.
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PMID:Pheophorbide a, a major antitumor component purified from Scutellaria barbata, induces apoptosis in human hepatocellular carcinoma cells. 1645 Feb 92

We studied inhibition of histone deacetylases (HDACs), which results in the unraveling of chromatin, facilitating increased gene expression. ITF2357, an orally active, synthetic inhibitor of HDACs, was evaluated as an anti-inflammatory agent. In lipopolysaccharide (LPS)-stimulated cultured human peripheral blood mononuclear cells (PBMCs), ITF2357 reduced by 50% the release of tumor necrosis factor-alpha (TNFalpha) at 10 to 22 nM, the release of intracellular interleukin (IL)-1alpha at 12 nM, the secretion of IL-1beta at 12.5 to 25 nM, and the production of interferon-gamma (IFNgamma) at 25 nM. There was no reduction in IL-8 in these same cultures. Using the combination of IL-12 plus IL-18, IFNgamma and IL-6 production was reduced by 50% at 12.5 to 25 nM, independent of decreased IL-1 or TNFalpha. There was no evidence of cell death in LPS-stimulated PBMCs at 100 nM ITF2357, using assays for DNA degradation, annexin V, and caspase-3/7. By Northern blotting of PBMCs, there was a 50% to 90% reduction in LPS-induced steady-state levels of TNFalpha and IFNgamma mRNA but no effect on IL-1beta or IL-8 levels. Real-time PCR confirmed the reduction in TNFalpha RNA by ITF2357. Oral administration of 1.0 to 10 mg/kg ITF2357 to mice reduced LPS-induced serum TNFalpha and IFNgamma by more than 50%. Anti-CD3-induced cytokines were not suppressed by ITF2357 in PBMCs either in vitro or in the circulation in mice. In concanavalin-A-induced hepatitis, 1 or 5 mg/kg of oral ITF2357 significantly reduced liver damage. Thus, low, nonapoptotic concentrations of the HDAC inhibitor ITF2357 reduce pro-inflammatory cytokine production in primary cells in vitro and exhibit anti-inflammatory effects in vivo.
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PMID:The histone deacetylase inhibitor ITF2357 reduces production of pro-inflammatory cytokines in vitro and systemic inflammation in vivo. 1655 34

In traditional oriental medicine, Yin-Chen-Hao decoction is used for the remedy of liver diseases such as hepatitis, fatty liver, hepatocirrhosis and jaundice. However, despite extensive pharmacological study, the molecular mechanism of the anti-inflammatory effect of Yin-Chen-Hao decoction is poorly understood. In this study, we have investigated the pharmacological action on the mechanism of concanavalin A-induced T cell-dependent hepatitis in mice. Concanavalin A administration resulted in a severe liver injury. This was shown through increased levels of serum transaminase and lactic dehydrogenase, and increased liver DNA fragmentation and caspase-3 activity. Pretreatment with the aqueous extract from Yin-Chen-Hao decoction dose-dependently inhibited the elevation in transaminase and lactic dehydrogenase activity, and reduced liver DNA fragmentation and caspase-3 levels. There was an improvement in histological changes including inflammatory infiltration, hepatocyte necrosis and degeneration, and Kupffer cell hyperplasia. In addition, Yin-Chen-Hao decoction significantly inhibited tumour necrosis factor-alpha (TNF-alpha) production in-vitro and in-vivo. Moreover, the activation of nuclear factor kappa B (NF-kappaB), which regulates TNF-alpha production, was blocked by Yin-Chen-Hao decoction in-vitro and in-vivo. In conclusion, Yin-Chen-Hao decoction was capable of regulating T-cell-mediated liver injury in-vivo. This event may have depended on the decrease of TNF-alpha production through the inhibition of NF-kappaB activation.
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PMID:Aqueous extract of Yin-Chen-Hao decoction, a traditional Chinese prescription, exerts protective effects on concanavalin A-induced hepatitis in mice through inhibition of NF-kappaB. 1664 Aug 37

The effects of dietary corn bran hemicellulose (CBH) and neomycin (Neo) on hepatic caspase-3 activity and glycoprotein concentration were investigated to explore the possible mechanism of the alleviative action of dietary CBH and Neo on the development of D-galactosamine (GalN)-hepatitis. Rats were fed a diet containing 5% CBH with or without neomycin (Neo) for 7 or 14 d. On the last day of feeding, the rats were treated with GalN (400 mg/kg body weight, i.p.), and their plasma transaminase activities, hepatic glycoprotein concentrations and hepatic caspase-3 activities were determined 6 or 24 h later. Although the elevations of plasma transaminase activities were suppressed by CBH or Neo 24 h after GalN-treatment, the activities were not affected by CBH or Neo at an early stage (6 h) of GalN action. At 6 h, hepatic caspase-3 activity was elevated by CBH diet alone as high as that of the GalN-injected control-diet group, and the activity was not elevated further by GalN. At the same time, both GalN-treatment and CBH feeding reduced the hepatic glycoprotein (Mw. 64,000-74,000) concentration, but Neo did not affect the caspase activity or the glycoprotein concentration. These results suggest that dietary CBH elevates hepatic caspase-3 activity and reduces hepatic glycoprotein concentration, and may imply that CBH would suppress GalN-hepatitis not at the early- or middle-step of apoptosis but at the late-step of apoptosis or necrosis, although the relation between these phenomena and the alleviative effects of CBH and Neo on GalN-induced hepatitis is yet to be clarified.
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PMID:Effects of dietary corn bran hemicellulose and neomycin on hepatic caspase-3 activity and glycoprotein concentration in rats treated with or without D-galactosamine. 1680 89


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