Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

2-Deoxy-D-galactose, in a dose of 3 mmol/kg, was administered intraperitoneally twice daily to young rats for periods up to 12 weeks. This dosage schedule resulted in recurrent phosphate trapping predominantly in liver. UTP deficiency was excluded by simultaneous uridine injections. Phosphate trapping was caused by the rapid accumulation of 2-deoxy-D-galactose 1-phosphate and was most pronounced in liver but also demonstrated in small intestine, brain, spleen, and thymus. The marked, although transient, drop in the hepatic content of inorganic phosphate triggered the catabolism of adenine nucleotides and a loss of ATP. Other metabolic pathways affected by phosphate deficiency include glycogenolysis and glycolysis. Increasing with time, repeated doses of the galactose analog led to retardation and arrest of growth, hepatomegaly, and splenomegaly. The average relative liver and spleen weights were elevated 2.5- and 4.5-fold, respectively, after 12 weeks of treatment. Liver damage was indicated by hyperbilirubinaemia and a progressive rise in the activity in plasma of sorbitol dehydrogenase, alkaline phosphatase, and gamma-glutamyltransferase. Examination by light and electron microscopy showed increasing numbers of vacuoles, surrounded by a single membrane, in hepatocytes, sinusoidal endothelial cells, and Kupffer cells. Focal cytoplasmic degeneration in hepatocytes was occasionally indicated by formation of autophagic vacuoles and finger print lysosomes. Hepatocytes of 2-deoxy-D-galactose-treated rats showed a dissociation and fragmentation of the rough endoplasmic reticulum. Sinusoidal endothelial cells and Kupffer cells were markedly enlarged, the latter contained a PAS-positive but amylase resistant substance. Extrahepatic changes included an increased occurrence of vacuolated cells in thymus. Phosphate trapping and its metabolic consequences are common phenomena in the experimental injury induced b 2-deoxy-D-galactose and in some hereditary diseases such as uridylyltransferase deficiency galactosaemia, fructose intolerance and glucose-6-phosphatase deficiency.
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PMID:Consequences of recurrent phosphate trapping induced by repeated injections of 2-deoxy-D-galactose. Biochemical and morphological studies in rats. 4 10

The effects of orotic acid consumption on hepatic lipid and nucleotide metabolism were examined concurrently in the rat. When orotic acid was fed at 1.0%, fatty liver development was evident by day 7 but not by day 3, whereas a decreased purine/pyrimidine ratio of hepatic acid-soluble nucleotides was noted by day 3. As nucleotide changes preceded hepatic fat accumulation, they could be a contributing factor in the etiology of fatty liver. When fed for 10 days, rats did not accumulate hepatic fat on a diet containing 0.1%, but did on 0.5 and 1.0%; similarly, the purine/pyrimidine ratio was not significantly affected on 0.1% but was decreased on both 0.5 and 1.0% orotic acid. These results indicate that orotic acid alters both hepatic lipid and nucleotides when consumed by rats at a level above 0.1%. As measured in these studies, hepatomegaly did not always accompany hepatic steatosis and appeared to be a subsequent development. In addition, L-dihydroorotate was shown to be as effective as orotic acid in increasing hepatic weight and lipid whereas uridine was ineffective.
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PMID:Orotic acid-induced metabolic changes in the rat. 736 48

Treatment of male Wistar rats with hexachlorobenzene (HCB) (1000 mg/kg b.w.) for 3-30 days decreases circulating levels of thyroxine (T4) but does not affect triiodothyronine (T3). Time courses were determined for 5' deiodinase type I (5' D-I) activity in thyroid, liver, and kidney and 5' deiodinase type II (5' D-II) activity in brown adipose tissue (BAT) to test the possibility that increased deiodinase activity might contribute to the maintenance of the serum T3 level. Specific 5' D-I activity was increased in the thyroid at 21 days and thereafter. No significant changes were observed in the liver, however, total 5' D-I activity in this tissue was increased at 30 days of treatment as a consequence of liver weight enhancement. HCB decreased kidney 5' D-I activity after 15 days, and BAT 5' D-II activity after 21 days of treatment. Total body 5' D-I activity was significantly increased by 30 days of HCB-treatment. HCB increased the activity of hepatic T4 uridine diphosphoglucuronosyl transferase (UDPGT) in a time-dependent manner, without changes in T3 UDPGT. We propose that increased T4 to T3 conversion in the thyroid and in the greatly enlarged liver may account for the maintenance of serum T3 concentration in hypothyroxinemic HCB-treated rats.
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PMID:The role of type I and type II 5' deiodinases on hexachlorobenzene-induced alteration of the hormonal thyroid status. 1566 63

Galactosemia is a rare autosomal recessive disorder of galactose metabolism, which occurs as a consequence of a deficiency of one of these three enzymes: galactokinase, galactose-1-phosphate uridyltransferase, and uridine diphosphate galactose-4-epimerase, leading to elevated level of galactose and its metabolites in blood. The presented case was a 2-month-old, Thai female infant with persistent cholestatic jaundice, bilateral posterior subcapsular cataracts, and hepatomegaly. Laboratory investigations showed slightly elevated serum aminotransferase, and increased urinary excretion of galactose, galactitol and galactonate (by urine gas chromatography/mass spectrometry). These findings indicated an error in galactose metabolism. Soy-based formula was introduced to the patient. Clinical and laboratory results were improved after a few months of treatment. Genetic counseling was provided to the family for 25% of recurrence risk. Prenatal diagnosis is not established in Thailand.
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PMID:Galactosemia in Thai patient at Phramongkutklao Hospital: a case report. 1685 69

Conazoles are a class of fungicides used as pharmaceutical and agricultural agents. In chronic bioassays in rats, triadimefon was hepatotoxic and induced follicular cell adenomas in the thyroid gland, whereas, propiconazole and myclobutanil were hepatotoxic but had no effect on the thyroid gland. These conazoles administered in the feed to male Wistar/Han rats were found to induce hepatomegaly, induce high levels of pentoxyresorufin-O-dealkylase, increase cell proliferation in the liver, increase serum cholesterol, decrease serum T3 and T4, and increase hepatic uridine diphosphoglucuronosyl transferase activity. The goal of the present study was to define pathways that explain the biologic outcomes. Male Wistar/Han rats (3 per group), were exposed to the 3 conazoles in the feed for 4, 30, or 90 days of treatment at tumorigenic and nontumorigenic doses. Hepatic gene expression was determined using high-density Affymetrix GeneChips (Rat 230_2). Differential gene expression was assessed at the probe level using Robust Multichip Average analysis. Principal component analysis by treatment and time showed within group sample similarity and that the treatment groups were distinct from each other. The number of altered genes varied by treatment, dose, and time. The greatest number of altered genes was induced by triadimefon and propiconazole after 90 days of treatment, while myclobutanil had minimal effects at that time point. Pathway level analyses revealed that after 90 days of treatment the most significant numbers of altered pathways were related to cell signaling, growth, and metabolism. Pathway level analysis for triadimefon and propiconazole resulted in 71 altered pathways common to both chemicals. These pathways controlled cholesterol metabolism, activation of nuclear receptors, and N-ras and K-ras signaling. There were 37 pathways uniquely changed by propiconazole, and triadimefon uniquely altered 34 pathways. Pathway level analysis of altered gene expression resulted in a more complete description of the associated toxicological effects that can distinguish triadimefon from propiconazole and myclobutanil.
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PMID:Transcriptional profiles in liver from rats treated with tumorigenic and non-tumorigenic triazole conazole fungicides: Propiconazole, triadimefon, and myclobutanil. 1717 89