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)

Different groups of rats suffering from galactosamine hepatitis or ANIT-cholestasis received 200 mg galactose either by 5 minutes intravenous infusion or via a gastric tube. Blood galactose concentrations were measured for a time period of 1.5 hrs. after intravenous administration and the galactose elimination capacity (GEC) was calculated. After oral administration the galactose blood concentrations were determined for a period of 3.5 hrs. and the oral galactose clearance was estimated. After termination of both types of galactose loading the activity of the galactokinase (EC 2.7.1.6.) was determined in total liver homogenate and compared either to the GEC or to the oral galactose clearance in vivo. Galactokinase activity in the liver increased in the group of animals with experimental cholestasis and was significantly reduced in the galactosamine treated group. In vivo these changes could be estimated much better by the GEC than by determination of the oral galactose clearance.
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PMID:[Intravenous and oral galactose loading of rats suffering from galactosamine hepatitis and ANIT-cholestasis; comparison of the kinetics in vivo and the galactose metabolism in the liver in vitro (author's transl)]. 52 47

Object of the investigation was to find out whether otherwise cholephilic metabolites are excreted via an alternative pathway into urine in experimental liver disease. Intraduodenal application of 14C-labelled hexobarbital in rats is followed by an immediate biliary excretion of metabolites in the range of 400 microgram/100 g bw/h. Using TLC these metabolites can be separated into a polar fraction (about 80% of total) and a non-polar fraction. Phenobarbital treatment leads to a decrease of the total biliary excretion of metabolites to about 200 microgram/100 g bw/h, the metabolite pattern remaining unchanged. Animals with a mild form of GalN-hepatitis had a moderate reduction of bile flow and a total metabolite output of 40 microgram/100/gbw/h. The metabolite pattern showed a decrease mainly of the polar fraction. In animals with an early stage of ANIT cholestasis a 50% reduction of bile flow was associated with a total metabolite excretion of only 20 microgram/100 g bw/h and polar metabolites were nearly absent. In both types of experimental liver disease in corresponding urine samples otherwise cholephilic metabolites appeared. The results obtained show that clinically moderate stages of experimental liver disease lead to a significantly diminished output especially of polar 14C-hexobarbital-metabolites into the bile, which can, therefore, appear in the urine instead.
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PMID:Alternative transport pathways of cholephilic 14C-hexobarbital metabolites in rats with experimental hepatitis and cholestasis. 54 23

Administrations of hepatotoxicants namely carbon tetrachloride (CCl4:0.4 ml in 1.2 ml of liquid paraffin) and ANIT (1 ml of 1.5% solution in liquid paraffin) in Charles foster rats (force fed) and D-galactosamine (8 mg in water per swiss albino mouse, ip) induce the release of TNF-alpha in case of CCl4 and D-galactosamine. High TNF-alpha level was observed up to 48 hr in CCl4 and up to 24 hr in D-galactosamine treated animals. Elevated levels of biochemical like ALP and SGPT are also recorded. TNF-alpha level can be measured of tissue damage and prognosis in case of hepatitis.
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PMID:Induction of tumour necrosis factor alpha in experimental animals treated with hepatotoxicants. 145 48

Each of 6 rats with a low grade of ANIT-cholestasis and a low grade of GalN-hepatitis received either 3 mg Lidocain i.v. or 24 mg Lidocain orally. The plasma concentrations of Lidocain were measured over a period of 3 1/2 hrs. The systemic clearance of Lidocain (Cli.v. = Di.v. divided by AUCi.v.) was significantly increased on ANIT-cholestasis (17 +/- 3) and GalN-hepatitis rats (13 +/- 2) (control rats: 7 +/- 1 ml/min x 100 g bw). Oral clearance of Lidocain (Clor = Dor divided by AUCor) was not significantly different in the three respective groups. In both groups with experimental liver disease the hepatic blood flow--calculated by comparing the systemic to the oral clearance--was significantly increased (22 +/- 4 and 19 +/- 3 vs 8 +/- 1 ml/min x 100 g bw). Due to this increase, the hepatic extraction ratio of Lidocain was significantly decreased (ANIT-cholestasis 0.73 +/- 0.07; GalN-hepatitis 0.74 +/- 0.05; controls 0.85 +/- 0.03). Because of an increase of systemic Lidocain clearance, no toxic plasma concentrations were observed.
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PMID:[Lidocain clearance after oral and intravenous application in rats with low grade ANIT-cholestasis and galactosamine-induced hepatitis (author's transl)]. 743 56

1-Naphthylisothiocyanate (ANIT), but not 2-naphthylisothiocyanate (BNIT), produces cholangiolitic hepatitis in rats after a single, oral administration. The mechanisms responsible for the disparate toxic outcomes for these closely related structural isomers are not fully understood. Recent reports suggest that ANIT-induced hepatotoxicity is dependent upon the formation and biliary excretion of a reversible glutathione-ANIT conjugate. To understand better the relationship between hepatic glutathione, secretion into bile and hepatotoxicity, the bile concentrations and hepatotoxicities of ANIT and BNIT were examined in rats with and without pretreatment with buthionine sulfoximine (BSO). ANIT (100 mg/kg, p.o.) caused a 3-fold elevation of plasma alanine aminotransferase activity (ALT), a 6-fold elevation of total plasma bilirubin, and a > 90% reduction in bile flow 24 hr after administration. BNIT, at this same dose and route of administration, did not alter significantly these markers of liver injury. Accumulation of ANIT and BNIT in bile occurred with the same temporal characteristics; however, BNIT accumulated to markedly larger concentrations (292 +/- 83 and 235 +/- 100 microM BNIT and 78 +/- 19 and 29 +/- 13 microM ANIT at 1 and 4 hr, respectively). The accumulation of ANIT and BNIT in bile was coincident with a > 2-fold elevation of reduced glutathione in bile. Pretreatment of rats with BSO decreased hepatic glutathione concentration and reduced the concentration of naphthylisothiocyanates in bile by 85%. Associated with this reduction was an attenuation of ANIT hepatotoxicity. Altogether, these findings indicate that both ANIT and BNIT accumulate in bile in a glutathione-dependent manner, yet they yield different hepatotoxic outcomes. Therefore, the disparity in hepatotoxicities observed with these isomers is not related to a difference in ability to enter bile. Other differences, such as in metabolism, chemical reactivity, conjugate stability and/or cytotoxic potential to bile duct epithelial cells may be more important determinants of hepatotoxicity.
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PMID:Naphthylisothiocyanate disposition in bile and its relationship to liver glutathione and toxicity. 750 98

1-Naphthylisothiocyanate (ANIT) produces cholangiolitic hepatitis in rats. This injury is characterized by periportal bile duct and hepatic parenchymal cell necrosis with inflammatory cell involvement. In contrast, 2-naphthylisothiocyanate (BNIT) does not induce cholangiolitic hepatitis. The mechanism(s) involved in ANIT-induced hepatic injury remain to be elucidated. To investigate this difference in toxicity further, we examined the cytotoxicity of ANIT and BNIT in primary rat hepatocyte cultures. Since neutrophils (PMNs) are required for the development of ANIT-induced cholangiolitic hepatitis in vivo, we also examined the potential for PMNs to modulate ANIT and BNIT cytotoxicity in rat hepatocyte-PMN cocultures. Both ANIT and BNIT injured rat hepatocytes within the range of concentrations examined (0-100 microM); however, BNIT was more potent. The presence of PMNs did not significantly influence the hepatocellular injury produced by either naphthylisothiocyanate (NIT). In an attempt to clarify the disparity between these results in vitro and observations reported in vivo, we examined, in hepatocyte PMN cocultures, the cytotoxic potential of bile collected from NIT-treated rats. Bile from BNIT-treated rats was markedly more cytotoxic to hepatocytes than was bile from ANIT-treated rats. As was observed in earlier experiments, the inclusion of PMNs had no effect on the hepatocellular toxicity of bile from NIT-treated rats. These findings prompted evaluation of the effect of NITs on rat PMNs. ANIT (1 and 10 microM) had no effect on phorbal myristate acetate (PMA)-induced superoxide production by PMNs, whereas BNIT (1 and 10 microM) markedly inhibited PMA-induced superoxide production. In contrast, ANIT and BNIT were equally effective at inhibiting f-met-leu-phe (fMLP)-induced PMN degranulation (beta-glucuronidase release). Altogether, the relative NIT toxicity observed in hepatocyte primary cultures is contrary to reports of hepatotoxic potential of these NITs in vivo. The PMN-dependence of ANIT hepatotoxicity in vivo was not reproduced in hepatocyte-PMN cocultures exposed to ANIT, suggesting that the PMN dependence in vivo involves factors not present in hepatocyte PMN cocultures. The greater PMN inhibitory effect of BNIT may, in part, underlie its inability to elicit the PMN-dependent liver injury in vivo that characterizes ANIT-induced cholangiolitic hepatitis.
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PMID:Cytotoxicity of naphthylisothiocyanates in rat hepatocyte-neutrophil cocultures. 970 17

The hepatoprotective effects of Tao-shang-tsao, Ixeris laevigata Sch.-Bip. var. oldhami Kitam., were studied on cholestatic hepatitis induced by alpha-naphthylisothiocyanate (ANIT, 100 mg/10 ml/kg, in olive oil, i.p.) and acute hepatitis induced by carbon tetrachloride (20% CCl4/olive oil, 1.5 ml/kg, i.p.) in rats by post-treatment with the crude methanolic extracts of I. laevigata (0.3, 1.0, and 2.0 g/kg) orally in the therapeutic model. Hepatoprotective activity was monitored by estimating the serum transaminases concentrations and histopathological changes in the livers of experimental rats. It was found that the I. laevigata extract significantly decreased the acute elevation of serum transaminases by biochemical examination. According to pathohistological studies in the liver of experimental rats, the crude I. laevigata extract ameliorates the central necrosis, fatty change or proliferation of bile duct epithelium focal necrosis caused by ANIT or CCl4-induced hepatitis rats.
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PMID:The evaluation of the therapeutic effect of tao-shang-tsao on alpha-naphthylisothiocyanate and carbon tetrachloride-induced acute liver damage in rats. 1115 49

The hepatoprotective effects of Ixeris laevigata Sch-Bip. var. oldhami Kitam. (IL) were studied on cholestatic hepatitis induced by alpha-naphthylisothiocyanate (ANIT, 100 mg/10 mL/kg, in olive oil, i.p.) and acute hepatitis induced by carbon tetrachloride (20% CCl(4)/olive oil, 1.5 mL/kg, i.p.) in rats. Hepatoprotective activity was monitored by estimating the serum transaminases levels and the histopathological changes in the livers of experimental rats. The pretreatment of animals with IL, extract (0.3-2.0 g/kg orally) significantly inhibited the acute elevation of serum transaminases, as well as the hepatotoxin-induced histopathological changes in the livers of the experimental rats.
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PMID:Preventive effect of the Taiwan folk medicine Ixeris laevigata var. oldhami on alpha-naphthyl-isothiocyanate and carbon tetrachloride-induced acute liver injury in rats. 1193 39

Metabonomics involves the quantitation of the dynamic multivariate metabolic response of an organism to a pathological event or genetic modification [J.K. Nicholson, J.C. Lindon, E. Holmes, Xenobiotica 29 (1999) 1181-1189]. The analysis of these data involves the use of appropriate multivariate statistical methods; Principal Component Analysis (PCA) has been documented as a valuable pattern recognition technique for 1H NMR spectral data [J.T. Brindle, H. Antti, E. Holmes, G. Tranter, J.K. Nicholson, H.W. Bethell, S. Clarke, P.M. Schofield, E. McKilligin, D.E. Mosedale, D.J. Grainger, Nat. Med. 8 (2002) 1439-1444; B.C. Potts, A.J. Deese, G.J. Stevens, M.D. Reily, D.G. Robertson, J. Theiss, J. Pharm. Biomed. Anal. 26 (2001) 463-476; D.G. Robertson, M.D. Reily, R.E. Sigler, D.F. Wells, D.A. Paterson, T.K. Braden, Toxicol. Sci. 57 (2000) 326-337; L.C. Robosky, D.G. Robertson, J.D. Baker, S. Rane, M.D. Reily, Comb. Chem. High Throughput Screen. 5 (2002) 651-662]. Prior to PCA the raw data is typically processed through four steps; (1) baseline correction, (2) endogenous peak removal, (3) integration over spectral regions to reduce the number of variables, and (4) normalization. The effect of the size of spectral integration regions and normalization has not been well studied. The variability structure and classification accuracy on two distinctly different datasets are assessed via PCA and a leave-one-out cross-validation approach under two normalization approaches and an array of spectral integration regions. The first dataset consists of urine from 15 male Wistar-Hannover rats dosed with ANIT measured at five time points, mimicking drug-induced cholangiolitic hepatitis [D.G. Robertson, M.D. Reily, R.E. Sigler, D.F. Wells, D.A. Paterson, T.K. Braden, Toxicol. Sci. 57 (2000) 326-337; J.P. Shockcor, E. Holmes, Curr. Top. Med. Chem. 2 (2002) 35-51; N.J. Waters, E. Holmes, A. Williams, C.J. Waterfield, R.D. Farrant, J.K. Nicholson, Chem. Res. Toxicol. 14 (2001) 1401-1412]. The second data is serum samples from young male C57BL/6 mice subjected to instillation of pancreatic elastase producing emphysema type symptoms [C. Kuhn, S.Y. Yu, M. Chraplyvy, H.E. Linder, R.M. Senior, Lab. Invest. 34 (1976) 372-380; C. Kuhn, R.M. Senior, Lung 155 (1978) 185-197]. This study indicates that independent of the normalization method the classification accuracy achieved from metabonomic studies is not highly sensitive to the size of the spectral integration region. Additionally, both datasets scaled to mean zero and unity variance (auto-scaled) have higher variability within classification accuracy over spectral integration window widths than data scaled to the total intensity of the spectrum. Of the top 10 latent variables for the ANIT dataset the auto-scale normalization has standard deviations larger than the total-scale in seven cases. In the case of the elastase all standard deviations are larger for the auto-scaling.
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PMID:A study of spectral integration and normalization in NMR-based metabonomic analyses. 1599 Feb 65

The protective effects of anthraquinones from Rhubarb, a Chinese herbal medicine, consisting of the root and rhizome of Rheum palmatum L., R. tanguticum Maxim. Ex Balf., or R. officinale Baill. (family Polygonaceae) were investigated and compared in rats with liver injury induced by alpha-naphthylisothiocyanate. alpha-Naphthylisothiocyanate was given intragastrically in rats, liver injury with cholestasis developed within 36 hrs, as indicated by characteristic serum levels of glutamate-pyruvate transaminase, glutamic oxaloacetic transaminase, total bilirubin, direct bilirubin, alkaline phosphatase, gamma-glutamyltransferase and total bile acid. The intragastrical administration of rhein, aloe-emodin and physione to alpha-naphthylisothiocyanate-treated rats reduced significantly the serum level of both glutamate-pyruvate transaminase, glutamic oxaloacetic transaminase and the serum total bilirubin, direct bilirubin, alkaline phosphatase, gamma-glutamyltransferase and total bile acid. For all hepatic biochemical markers and cholestasis index, rhein was most efficient. By comparison, the administration of emodin and chrysophanol did not reduce the serum levels of hepatic enzymes glutamate-pyruvate transaminase and glutamic oxaloacetic transaminase but decreased the levels of serum total bilirubin, direct bilirubin, alkaline phosphatase, gamma-glutamyltransferase, and total bile acid, showing their partial protective effects on cholestatic liver injury. The liver in alpha-naphthylisothiocyanate-treated rats showed cholangiolitic hepatitis characterized by intrahepatic cholestasis, necrosis of hepatocytes and biliary epithelial cells and bile obstruction. The concurrent intragastrical administration of rhein reduced the severity of all morphological alteration, especially the neutrophil infiltration and sinusoid congestion. Rhein, aloe-emodin, and physione all exhibited protective effects on hepatocytes and cholangiocytes against alpha-naphthylisothiocyanate-induced damage, whereas emodin and chrystophanol provided partial protection.
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PMID:Investigations of free anthraquinones from rhubarb against alpha-naphthylisothiocyanate-induced cholestatic liver injury in rats. 1938 47


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