Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Choline Deficiency”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 235 records · Page 13Linked to original sources
PubMed1998

Herbal medicine Sho-saiko-to (TJ-9) prevents liver fibrosis and enzyme-altered lesions in rat liver cirrhosis induced by a choline-deficient L-amino acid-defined diet.

BACKGROUND/AIM: A herbal medicine, Sho-saiko-to (TJ-9), has recently been orally administered to patients with chronic liver disease in Japan and has been reported to inhibit the development of hepatocellular carcinoma. The aim of this study was to investigate whether TJ-9 has an inhibitory effect on the development of preneoplastic lesions and liver fibrosis in rats. METHODS: The effects of the TJ-9 were examined using the choline-deficient L-amino acid-defined (CDAA) diet-induced liver fibrosis model in 16-week-old male Wistar rats. RESULTS: TJ-9 (1% w/w) prevented fibrosis, as indicated by reduced hydroxyproline content in the liver and inhibition of the increase in a serum marker of fibrosis (hyaluronic acid), without reducing the increase in serum alanine aminotransferase and aspartate aminotransferase. TJ-9 also reduced the expression of type III procollagen alpha 1 mRNA in the liver, as well as the proliferation of myofibroblast-like cells (activated stellate cells, activated Ito cells). Furthermore, TJ-9 reduced the number of preneoplastic lesions, detected as enzyme-altered (glutathione S-transferase placental form-positive) lesions, in the liver. CONCLUSIONS: These results indicate that the herbal medicine Sho-saiko-to (TJ-9) prevents fibrosis as well as preneoplastic lesions, not by inhibiting hepatocyte cell death but by inhibiting the activation of stellate cells, which are considered to be the main collagen-producing cells, leading to a reduction in the development of preneoplastic lesions.

Amino Acids↗
PubMed1989

Effect of feeding a choline-deficient diet on the hepatic nuclear response to tryptophan in the rat.

In earlier studies the acute administration of tryptophan (TRP) to rats was reported to induce enhanced in vivo [14C]orotate-labeled hepatic nuclear RNA release in vitro. This change was considered to possibly be related to the induction of more and larger gamma-glutamyl transpeptidase-positive foci in the livers of rats treated with diethylnitrosamine and fed long-term elevated TRP in a choline-supplemented (CS) but not in a choline-deficient (CD) diet (comparisons with respective controls). In this study we investigated whether feeding a CD compared to a CS diet for 1 week would affect selected hepatic nuclear responses to TRP. Rats fed the CS but not the CD diet and tube-fed TRP 10 min before being killed revealed enhanced labeled hepatic nuclear RNA release in vitro. In all experiments, comparisons were made with the control groups (rats fed the CS or stock diet). When rats were fed elevated TRP (2%) in the diets (CS or CD) for 1 week, labeled hepatic nuclear RNA release was increased with the CS + TRP but not with the CD + TRP diet group. [3H]TRP binding to hepatic nuclei in vitro revealed no change in the CS + TRP group, decreased in the CD group, and markedly increased in the CD + TRP group in comparison with the control (CS) group. Hepatic nuclear nucleoside triphosphatase activity was increased only in the CS + TRP group while hepatic nuclear poly(A) polymerase activity was increased in the CS + TRP and in the CD +/- TRP groups. Serum cholesterol and triglycerides were decreased in the CD group and increased to control levels in the CD + TRP group.

Animals↗
PubMed1981

The effects of ethionine administration and choline deficiency on protein carboxymethylase activity in mouse pancreas.

Protein carboxymethylase of mouse pancreas is both soluble (70%) and particulate (30%). The Km for S-adenosylmethionine is 7.5 x 10(-7) M and the Ki for S-adenosylethionine is 1.3 . 10(-5) M. Administration of an ethionine containing diet results in a decrease in protein carboxymethylase activity. Ethionine ingestion also increases pancreatic amylase content by interfering with digestive enzyme discharge. The reciprocal changes in amylase content and protein carboxymethylase activity can be detected within 12 h of commencing the ethionine administration and are enhanced by simultaneous choline deficiency. These studies support the hypothesis that protein carboxymethylase plays an important role in secretion of exportable material. Inhibition of pancreatic protein carboxymethylase activity in vivo may be one important mechanism by which ethionine interferes with digestive enzyme discharge.

Adenosine↗
PubMed1994

Inhibitory effects of 2-O-octadecylascorbic acid and other vitamin C and E derivatives on the induction of enzyme-altered putative preneoplastic lesions in the livers of rats fed a choline-deficient, L-amino acid-defined diet.

Effects of a lipophilic derivative of vitamin C, 2-O-octadecylascorbic acid (CV-3611), as well as its parent L-ascorbic acid (AscA), DL-alpha-tocopherol (alpha-T) and its hydrophilic derivative, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox), on the number and size of gamma-glutamyltransferase (GGT)-positive putative preneoplastic lesions were examined and compared with their influences on 8-hydroxyguanine formation in DNA and 2-thiobarbituric acid-reacting substance generation in the livers of rats fed a choline-deficient, L-amino acid-defined (CDAA) diet for 12 weeks. A total of 90 male Fischer 344 rats, 6 weeks old, were divided into 18 groups each consisting of five rats. Group 1 received the CDAA diet alone; Groups 2, 3 and 4 received the CDAA diet containing respectively 0.01, 0.05 and 0.10% CV-3611; Groups 5-7, 8-10 and 11-13 similarly received the CDAA diet containing AscA, alpha-T and Trolox, respectively, at these same low, middle and high concentrations; Group 14 received a choline-supplemented, L-amino acid-defined (CSAA) diet alone; Groups 15-18 were given the CSAA diet containing CV-3611, AscA, alpha-T and Trolox, respectively, all at the 0.10% level. While all four vitamin derivatives exerted inhibitory effects on all four parameters, in each case dose-dependently, CV-3611 demonstrated the most pronounced effects. The present results indicated that lipophilic vitamin C derivatives may be particularly effective chemopreventive agents against CDAA diet-associated, oxidative stress-related hepatocarcinogenesis via its superior antioxidative properties.

Amino Acids↗
PubMed2004

Pioglitazone prevents hepatic steatosis, fibrosis, and enzyme-altered lesions in rat liver cirrhosis induced by a choline-deficient L-amino acid-defined diet.

Non-alcoholic steatohepatitis (NASH) may progress to liver cirrhosis, and NASH patients with liver cirrhosis have a risk of development of hepatocellular carcinoma. Peroxisome proliferator-activated receptor (PPAR) gamma ligand has recently been reported to have improved the condition of patients with NASH. The aim of this study was to investigate whether pioglitazone, a PPARgamma ligand, has any influence on the animal model of NASH as well as isolated hepatic stellate cells. In vivo, the effects of pioglitazone were examined using the choline-deficient L-amino acid-defined (CDAA)-diet liver fibrosis model. After two weeks, pioglitazone improved hepatic steatosis, prevented liver fibrosis, and reduced preneoplastic lesions in the liver after 10 weeks. Pioglitazone reduced the expression of TIMP-1 and TIMP-2 mRNA without changing MMP-13 mRNA expression compared to the liver fed a CDAA diet alone. In vitro, pioglitazone prevented the activation of hepatic stellate cells resulting in reducing the expression of type I procollagen, MMP-2, TIMP-1, and TIMP-2 mRNA with increased MMP-13 mRNA expression. These results indicate that pioglitazone may be one of the candidates for the benefit drugs for the liver disease of patients with NASH.

Amino Acids↗
PubMed1985

Monoclonal antibodies recognizing oval cells induced in the liver of rats by N-2-fluorenylacetamide or ethionine in a choline-deficient diet.

In this paper, we describe the production of a panel of monoclonal antibodies which define antigens which distinguish between hepatocytes and oval cells. These antibodies were obtained from hybridomas constructed from the spleens of mice immunized by a novel protocol designed to suppress response to unwanted or immunodominant epitopes. Of the antibodies obtained, four, 258.7, 270.11, 258.34, and 270.38, were directed to antigens of morphologically defined oval cells, while two, 258.26 and 270.26, defined cytoplasmic antigens of hepatocytes. Examination of frozen sections of normal, regenerating adult and fetal liver and livers from rats fed 2-acetylaminofluorene or ethionine in a choline-deficient diet indicates that morphologically defined oval cells may in fact comprise a phenotypically complex set of cells composed of at least three antigenically distinct subpopulations. The patterns of expression of the antigens defined by these antibodies suggest two possible pathways of liver cell differentiation.

2-Acetylaminofluorene↗
PubMed1986

Suppression of choline-deficient diet-induced hepatocyte membrane lipid peroxidation in rats by the peroxisome proliferators 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio(N-beta-hydroxyethyl)- acetamide and di(2-ethylhexyl)phthalate.

Many hypolipidemic peroxisome proliferators have been shown to induce liver tumors in rats after long-term feeding. In short-term assays, however, some of them prevent the development of gamma-glutamyl transpeptidase-positive foci, the putative preneoplastic lesions, in the liver of carcinogen-initiated rats and inhibit the promoting effect of a choline-deficient (CD) diet on these lesions. The CD diet-induced lipid peroxidation in the liver has been implicated as one of the underlying mechanisms of the promoting effect. In the present study, the effects of 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio(N-beta-hydroxyethyl)acetamid e (BR931) and di(2-ethylhexyl)phthalate (DEHP) on CD diet-induced liver membrane lipid peroxidation were investigated by determining the extents of conjugated diene formation. No evidence of lipid peroxidation was detected in the microsomal lipids of the liver after administration of BR931 or DEHP at concentrations of 0.16% and 1%, respectively, for 1, 2, and 4 wk. When added to a CD diet, both BR931 and DEHP effectively protected against the diet-induced lipid peroxidation. There was an increase in cellular glutathione levels after 4 wk and an increase in catalase activity after 2 wk in the liver of rats fed BR931 or DEHP. The levels of activity of the glutathione peroxidases and glutathione-s-transferase were significantly reduced. The results suggest that, in the acute stage, hypolipidemic peroxisome proliferator-induced effects of excess production of H2O2 and potential lipid peroxidation are balanced by stimulation of some cellular detoxifying systems. The inhibition of lipid peroxidation by hypolipidemic peroxisome proliferators may account for their inhibitory effects on the CD diet-induced promotion of preneoplastic foci.

Animals↗
PubMed2006

Hepatic oval cell response to the choline-deficient, ethionine supplemented model of murine liver injury is attenuated by the administration of a cyclo-oxygenase 2 inhibitor.

Oval cell proliferation precedes neoplasia in many rodent models of hepatocellular carcinoma and prevention of this proliferative response can reduce the risk of subsequent carcinoma. This study aimed to determine whether a selective cyclo-oxygenase-2 (COX-2) inhibitor, SC-236, affects (i) the oval cell response to liver injury in a mouse model of hepatocarcinogenesis and (ii) an oval cell line. Four-week-old mice were fed either normal chow or a choline deficient, ethionine supplemented (CDE) diet in the presence or absence of SC-236. Liver histology and oval cell numbers were determined after 2, 4, 12 and 52 weeks of treatment. Oval cells were scored using morphological criteria and positive immuno-staining for the M(2)-isozyme of pyruvate kinase (M2PK) or A6. An immortalized oval cell line (PIL-2) was used to study the in vitro effects of SC-236 on oval cell proliferation, apoptosis and Akt phosphorylation. The percentage of M2PK-positive oval cells and COX-2-positive cells was reduced by 80% and 45%, respectively, in CDE-fed mice receiving SC-236 compared with CDE-fed animals not receiving SC-236. Some M2PK-positive oval cells were also COX-2 positive. The percentage of A6-positive cells was not affected by SC-236 administration to CDE-fed mice. Administration of SC-236 increased apoptosis as evidenced by a 73% increase in the number of TUNEL-positive cells at 2 weeks in CDE-fed mice. Primary oval cells and PIL-2 cells expressed COX-2. In vitro treatment of PIL-2 cells with SC-236 resulted in a dose-dependent preferential death of A6-negative cells. Administration of 25 and 50 microM Prostaglandin E(2) partially attenuated SC-236 induced cell death by 25%. In vitro oval cell death was associated with apoptosis and a 70% reduction in Akt phosphorylation. These results suggest that the SC-236 induced reduction of M2PK-positive oval cell numbers may be due to COX-2 dependent inhibition of Akt phosphorylation and induction of apoptosis.

Animals↗
PubMed1997

Choline deficiency selects for resistance to p53-independent apoptosis and causes tumorigenic transformation of rat hepatocytes.

The mechanisms which drive initiated cells to progress to form carcinomas are poorly understood. CWSV-1 rat hepatocytes, in which p53 protein is inactivated by SV40 large T antigen, respond by inducing p53-independent apoptosis when acutely switched to medium containing low choline (16% apoptotic at 48 h in 5 microM choline) as compared with controls (1% apoptotic at 48 h in 70 microM choline). The rate of apoptosis was inversely correlated with cellular phosphatidylcholine content. Choline deficiency (CD)-induced apoptosis is probably mediated by TGFbeta1 and reactive oxygen species, since immunoneutralization of TGFbeta1 in the medium or treatment with N-acetylcysteine (an antioxidant) or addition of neocuproine (a transition metal chelator) prevented CD-induced apoptosis. CWSV-1 hepatocytes could be gradually adapted to survive in 5 microM choline. CD-adapted cells had increased membrane phosphatidylcholine concentrations (compared with acute CD cells). Adapted cells acquired relative resistance to CD-induced apoptosis (7% of adapted cells compared with 19% of non-adapted cells were apoptotic at 48 h in 5 microM choline). They also became relatively resistant to another p53-independent form of apoptosis (TGFbeta1-induced). CD-adapted hepatocytes developed increased capability for anchorage-independent growth and formed tumors when transplanted into nude mice; passage-matched control hepatocytes did not possess these properties. Cell transformation was dependent on exposure to the selective pressure of CD apoptosis, as we observed that when CD apoptosis was inhibited with an antioxidant during adaptation, cells did not become anchorage independent. Acquisition by p53-deficient cells of resistance to p53-independent inducers of apoptosis (CD, TGFbeta1 and reactive oxygen species) may leave cells without another important apoptotic defensive barrier and may be responsible for the progression of initiated cells to frank carcinomas.

Animals↗
PubMed1998

Prevention by 1'-acetoxychavicol acetate of the induction but not growth of putative preneoplastic, glutathione S-transferase placental form-positive, focal lesions in the livers of rats fed a choline-deficient, L-amino acid-defined diet.

The effects of 1'-acetoxychavicol acetate (ACA) on endogenous rat liver carcinogenesis because of chronic feeding of a choline-deficient, L-amino acid-defined (CDAA) diet were examined. Male Fischer 344 rats, 6 weeks old, received the CDAA diet containing ACA at doses of 0, 0.005, 0.010 and 0.050% for 12 weeks and were then killed. ACA decreased the numbers of putative preneoplastic, glutathione S-transferase placental form (GST-P)-positive, focal lesions developing in the livers of rats fed the CDAA diet but did not alter their sizes. At the same time, ACA reduced the levels of 8-hydroxyguanine, a parameter of oxidative DNA damage, but did not significantly affect generation of 2-thiobarbituric acid-reacting substances, indicators of oxidative extra-DNA damage, or hepatocyte proliferation. Furthermore, ACA did not exert any significant effects on the numbers or sizes of GST-P-positive lesions in the livers of rats when administered between weeks 2 and 8 after initiation with a single i.p. dose of 200 mg/kg body wt of N-nitrosodiethylamine. These results indicate that ACA prevents the CDAA diet-associated induction of putative preneoplastic lesions by reduction of oxidative DNA damage but does not affect their subsequent growth.

Amino Acids↗
PubMed1990

Reduction in VLDL, but not HDL, in plasma of rats deficient in choline.

We have analyzed plasma lipoprotein levels in young male rats fed a choline-deficient diet for 3 days. We confirmed previous studies that choline deficiency promotes 6.5-fold accumulation of triacyglycerol in the liver (23.9 +/- 6.0 versus 3.69 +/- 0.92 mumol/g liver) and reduction of triacylglycerol concentration in plasma by 60% (0.17 +/- 0.04 versus 0.46 +/- 0.10 mumol/mL plasma). Agarose gel electrophoresis showed that the plasma very low density lipoprotein (VLDL) levels were reduced in choline-deficient rats, but the concentration of plasma high density lipoproteins (HDL) was not affected. Sodium dodecyl sulfate - polyacrylamide gel electrophoresis of fractionated plasma lipoproteins revealed that the concentrations of apolipoproteins (apo) BH, BL, and E in VLDL from choline-deficient rats were 37.1, 11.0, and 37.2% of normal levels, respectively. In contrast, the amount of apo A-I, the major one in HDL, was almost unchanged. Correspondingly, there were decreased lipid (mainly phosphatidylcholine and triacylglycerol) levels in VLDL from choline-deficient rats, but no change in the levels of phosphatidylcholine, cholesterol, and cholesterol ester in HDL. There were similar levels of apo B and E (components of VLDL) in homogenates of livers from normal and choline-deficient rats, as determined by immunoblotting. These results support the hypothesis that choline deficiency causes reduction of VLDL, but not HDL, levels in plasma as a consequence of impaired hepatic VLDL secretion.

Animals↗
PubMed2006

Effects of bezafibrate, PPAR pan-agonist, and GW501516, PPARdelta agonist, on development of steatohepatitis in mice fed a methionine- and choline-deficient diet.

We evaluated the effects of bezafibrate, a peroxisome proliferator-activated receptor (PPAR) pan-agonist, and GW501516, a PPARdelta agonist, on mice fed a methionine- and choline-deficient (MCD) diet, a model of non-alcholic steatohepatitis (NASH), to investigate (a) the efficacy of bezafibrate against non-alcholic steatohepatitis and (b) the relation between non-alcholic steatohepatitis and the functional role of PPARdelta. Bezafibrate (50 or 100 mg/kg/day) and GW501516 (10 mg/kg/day) were administered by gavage once a day for 5 weeks. Hepatic lipid contents, plasma triglyceride, high density lipoprotein (HDL)-cholesterol and alanine aminotransferase (ALT) concentrations were evaluated, as were histopathological changes in the liver and hepatic mRNA expression levels. Bezafibrate and GW501516 inhibited the MCD-diet-induced elevations of hepatic triglyceride and thiobarbituric acid-reactants contents and the histopathological increases in fatty droplets within hepatocytes, liver inflammation and number of activated hepatic stellate cells. In this model, bezafibrate and GW501516 increased the levels of hepatic mRNAs associated with fatty acid beta-oxidation [acyl-CoA oxidase (ACO), carnitine palmitoyltransferase-1 (CPT-1), liver-fatty acid binding protein (L-FABP) and peroxisomal ketothiolase], and reduced the levels of those associated with inflammatory cytokines or chemokine [transforming growth factor (TGF)-beta1, interleukin (IL)-6, IL-1beta, monocyte chemoattractant protein (MCP)-1, tumor necrosis factor (TNF) alpha and nuclear factor (NF)-kappaB1]. In addition, bezafibrate characteristically reduced the elevation in the level of plasma ALT, but enhanced that in plasma adiponectin and increased the mRNA expression levels of its receptors (adiponectin receptors 1 and 2). These results suggest that (a) bezafibrate (especially) and GW501516 might improve hepatic steatosis via an improvement in fatty acid beta-oxidation and a direct prevention of inflammation, (b) treatment with a PPARdelta agonist might improve non-alcholic steatohepatitis, (c) bezafibrate may improve non-alcholic steatohepatitis via activation not only of PPARalpha but also of PPARdelta, because bezafibrate is a PPAR pan-agonist.

Acyl-CoA Oxidase↗
PubMed1999

Hypomethylation of CpG sites and c-myc gene overexpression in hepatocellular carcinomas, but not hyperplastic nodules, induced by a choline-deficient L-amino acid-defined diet in rats.

We have investigated aberrant methylation of CpG nucleotides (CpG sites) and gene expression of c-myc during hepatocarcinogenesis induced by a choline-deficient, L-amino acid-defined (CDAA) diet in rats. Male Fischer 344 rats, 6 weeks old, were continuously given a CDAA diet for 50 and 75 weeks and then killed. Macroscopically detectable nodules, which were histologically confirmed to be hyperplastic nodules (HNs) or well-differentiated hepatocellular carcinomas (HCCs), were dissected free from the surrounding tissue. Normal control liver was obtained from 6-week-old rats. Methylation of CpG sites of the c-myc gene was investigated in bisulfite-treated DNA isolated from normal liver, HNs and HCCs. All 33 cytosines in the 5'-upstream region of the c-myc gene were fully methylated in control liver and the 4 HNs. In contrast, these cytosines were completely unmethylated in 5 HCCs. Examination of the c-myc expression by reverse transcription-polymerase chain reaction (RT-PCR) analysis also showed a marked increase as compared to the low levels in normal livers and HNs. These results suggest that hypomethylation of the c-myc gene might play a critical role in malignant transformation from HN to HCC during CDAA diet-induced hepatocarcinogenesis in rats.

Amino Acids↗