Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The parallelism between xanthurenuria and liver affections caused by protein and choline deficiency was studied. At the stages marking the development of lipohepatosis and fibrosis there occurred an intensive passage of xanthurenic acid. The intensity of xanthurenuria at the stage marking the appearance of hyperplastic nodes continued to gain strength. With progressive advance of pathological changes, which by the 9--12th months of the experiment reached the stage of a fully developed nodular cirrhosis xanthurenuria gradually stopped.
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PMID:[Xanthurenuria at different stages of liver lesion induced by protein and choline deficiency]. 43 33

Serum and liver total cholesterol and cholesterol esters were studied in rats of different stages of pathological process induced by a prolonged protein and choline deficiency. Depending upon the time of its application the protein-choline deficiency produced in rats a moderate fatty infiltration, a developed lipohepatosis, fibrosis and nodular liver cirrhosis. Application of the diet resulted in an increase in total cholesterol starting from the first days of developing fatty degeneration of the liver. This increase in total liver cholesterol is at the expense of the increase in cholesterol esters, accumulation of which appeared to be maximum at the stage of the cirrhosis development. In choline-deficient rats the concentration of serum total cholesterol proves to be similar to that in control animal receiving the basic diet, and the content of serum cholesterol esters is considserably decreased. The addition of choline to the cirrhosis-producing diet prevented the development of fatty infiltration, but could not avert disorders in cholesterol metabolism which resulted in an increase in serum total cholesterol with the free cholesterol fraction and a decrease in the cholesterol esters fraction with some accumulation of cholesterol esters in rats liver.
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PMID:[Content of total and esterified cholesterol in liver tissue and blood with chronic protein-choline deficiency]. 120 65

1. Rats were given a purified folate-deficient diet containing 5 g succinylsulphathiazole/kg for 4-5 months in two experiments. Control rats were supplemented with folic acid in the drinking-water. 2. Weight gain was much below normal in the folate-deprived rats after the first month. Very low folate levels were recorded in blood, liver and peripheral nerve (12-33% of control). In the central nervous system, including the cerebrospinal fluid, the folate depletion was less conspicuous (50-80% of control). Only marginal signs of anaemia were found and no signs of neurological dysfunction were detected, using nerve conduction velocity measurement and co-ordination tests. 3. Light and electron microscopy of the folate deficient liver revealed fatty infiltration, and enlargement of liver parenchymal cells, nuclei and nucleoli. There was often a considerable amount of bile ductular cells in the lobuli but no cirrhosis. The morphological changes resembled those observed in choline deficiency. 4. Phospholipid N-methylation in liver was depressed in folate-deficiency. This was probably due to a decreased availability of S-adenosylmethionine caused by the low concentrations of methylated folate in liver. Intraperitoneal administration of methionine did not normalize phospholipid methylation. 5. In folate deficiency the proportion of ethanolamine phosphoglyceride in liver was increased at the expense of choline phosphoglyceride, which is consistent with a decreased phospholipid methylation. Also an increase in liver triacylglycerol was noted, in accordance with the morphological observations. Brain lipid composition was unchanged. 6. After the injection of labelled ethanolamine, isotope accumulated in liver phosphoethanolamine in folate deficiency, probably due to an impairment of the CTP:ethanolaminephosphate cytidylyltransferase (EC 2.7.7.14) reaction. The mechanism of this impairment is discussed. 7. Although the low concentrations of folate was the main nutritional change in the deprived animals, changes with respect to vitamin B12 and maybe also choline cannot be excluded. We conclude that some of the changes in folate deficiency, i.e. fatty liver and decreased biosynthesis of liver phospholipids may be due to a precipitated deficiency of lipotropic agents, whereas other differences may be specific for deficiency of folate per se, such as changes in liver phospholipid fatty acids and some of the morphological aberrations.
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PMID:Effect of experimental folate deficiency on lipid metabolism in liver and brain. 708 22

The effects of alcohol on hepatic iron uptake and intestinal iron transport were studied in rats fed a nutritionally replete liquid diet containing varying quantities of ethanol. Results were compared with those from animals exposed to carbon tetrachloride (CCl4) to produce hepatocellular necrosis or a choline-deficient diet to produce steatosis and cirrhosis. A high ethanol intake for 4 or 10 weeks produced hepatic steatosis. CCl4 produced hepatocellular necrosis. Choline deficiency was associated with steatosis +/- cirrhosis. Intestinal iron transport was unaffected by ethanol, CCl4, or choline deficiency. Hepatic iron uptake was significantly depressed in rats consuming 11.7 g/kg/day ethanol (p < 0.01) for 4 weeks. Choline-deficient animals studied at 14 weeks also had significantly decreased hepatic iron uptake (p < 0.01); results were similar in the cirrhotic and noncirrhotic animals. Conversely, CCl4 exposure produced a significant 5-fold increase in hepatic iron uptake (p < 0.001). Results suggest that ethanol consumption, fatty liver, and cirrhosis are not responsible for any increase in iron absorption or of hepatic iron uptake in the rat model. Acute hepatocellular injury is followed by increased hepatic iron uptake.
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PMID:Effects of alcohol, carbon tetrachloride, and choline deficiency on iron metabolism in the rat. 827 76

Carcinogenesis may be effected not only through exposure to exogenous stimuli but also by genetic and epigenetic influences derived from endogenous factors. In the latter case, the mechanisms are still largely obscure because of the limited availability of appropriate in vivo experimental models. However, continuous feeding of a diet deficient in choline and methionine is well known to cause hepatocellular carcinomas (HCC) in rats in the absence of any known exogenous carcinogens and can serve as a good research model. A semi-synthetic, choline-deficient, L-amino acid-defined (CDAA) diet, containing practically no choline and low methionine, induces HCC with a background of fatty liver and hepatocyte death, subsequent regeneration and fibrosis resulting in cirrhosis. Using the CDAA diet, we have revealed the participation of oxidative injury to DNA and other subcellular components and of alteration in intrahepatic signal transduction pathways in the mechanisms underlying this rat liver carcinogenesis model. In the present paper, the current understanding of endogenous rat liver carcinogenesis, due to dietary choline deficiency, is reviewed.
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PMID:Endogenous liver carcinogenesis in the rat. 1063 23

Two groups of adult rats fed a choline-deficient diet supplemented with neomycin in their drinking water for 250 or 350 days were protected against the development of liver fibrosis and cirrhosis. At the termination of the study these animals weighed more than others not receiving neomycin. This difference in weight did not appear to be caused by a growth-promoting effect of neomycin but rather reflected the increased severity of liver disease and a resultant weight loss in animals not receiving neomycin. Protection by neomycin was cancelled when Salmonella typhosa endotoxin was added to the drinking water. It was concluded that the protective effect of neomycin was mediated by an alteration in the intestinal microflora resulting in a reduction in the numbers of organisms contributing to intraluminal endotoxin. In the presence of choline deficiency, absorption of intraluminal endotoxin may contribute to the development of fibrosis and cirrhosis.
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PMID:INFLUENCE OF NEOMYCIN AND INGESTED ENDOTOXIN IN THE PATHOGENESIS OF CHOLINE DEFICIENCY CIRRHOSIS IN THE ADULT RAT. 1415 Nov 3

Intestinal failure-associated liver disease develops in 40% to 60% of infants who require long-term total parenteral nutrition (TPN) for intestinal failure and 15% to 40% of adults on home parenteral nutrition. The clinical spectrum includes hepatic steatosis, cholestasis, cholelithiasis, and hepatic fibrosis. Progression to biliary cirrhosis and the development of portal hypertension and liver failure occurs in a minority but is more common in infants and neonates than in adults. The pathogenesis is multifactorial. In infants it is related to prematurity, low birth weight, duration of PN, short bowel syndrome requiring multiple laparotomies, and recurrent sepsis. Other important mechanisms include lack of enteral feeding, which leads to reduced gut hormone secretion; reduction of bile flow and biliary stasis, which leads to the development of cholestasis; and biliary sludge and gallstones, which exacerbate hepatic dysfunction. In adults, IFALD is less common and related to age, length of time on PN, total caloric intake, and lipid or glucose overload. In preterm infants, a deficiency of taurine or cysteine may play a role, whereas in both adults and children, choline deficiency may exacerbate IFALD. Lipid emulsions, choline deficiency, and manganese toxicity are associated with both hepatic steatosis and cholestasis in adults and children. Management strategies for the prevention of intestinal failure-induced liver disease include early enteral feeding, a multidisciplinary approach to the management of parenteral nutrition, and aseptic catheter techniques to reduce sepsis. The addition of choline, taurine, and cysteine to PN solutions may also play a role. Oral administration of ursodeoxycholic acid may improve bile flow and reduce gallbladder stasis. Survival after either isolated small bowel or combined liver and small bowel transplantation is approximately 50% at 5 years, making this an acceptable therapeutic option in adults and children with irreversible liver and intestinal failure.
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PMID:Intestinal failure-associated liver disease: what do we know today? 1647 75

From the mid-1950s, it was observed that liver injury by a variety of toxins greatly sensitized the host to the effects of administered lipopolysaccharide. In the nutritional cirrhosis of choline deficiency, and in acute toxic injury as well, the need for the presence of enteric endotoxin was demonstrated. The universality of this association was striking for almost all agents associated with liver injury. In addition, the presence of endotoxemia in human liver disease was documented in the 1970s, when the hypothesis was first proposed, and correlated with the severity of the disease. Despite imposing evidence of the critical role of enteric endotoxin in liver injury, it did not excite much interest in investigators until the 1980s. With the ability to study effects of alcohol in newer delivery systems, and an increased understanding of the role of Kupffer cells in the process, the original hypothesis has been accepted. This historical review details the progress of this novel concept of disease initiation and suggests future directions to bring potential therapies to the bedside.
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PMID:The role of intestinal endotoxin in liver injury: a long and evolving history. 2203 Aug 39

Choline deficiency (CD) increases susceptability of (he rat liver to a number of hepatocellular carcinogens with a wide diversity of structure and potency. While severe CD results in micronodular cirrhosis and enhanced tumor induction, even a mild deficiency, without cirrhosis is sufficient to result in the increased carcinogenic response. The effects of CD are in part mediated via modulation of microsomal and, possibly, cytosolic enzymes responsible for activation/deactivation of carcinogens. The B6C3F1 hybrid mouse is remarkably sensitive to initiation/promotion of liver tumors by many substances or conditions. Choline deficiency or partial hepatectomy alone, or in concert, markedly enhances liver tumor induction in the absence of any known carcinogen. These data indicate that the liver of this strain of mouse is "initiated" at or shortly after birth and can be promoted by non-carcinogenic substances or conditions.
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PMID:Choline Deficiency, Partial Hepatectomy, and Liver Tumors in Rats and Mice. 2809 26