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)

Recent results (3) indicate that 200 mg 3,4,3',4'-tetrachlorobiphenyl induces hepatomegaly accompanied by significant decreases in serum and hepatic retinoid content and hepatocyte morphologic alterations of proliferated and vesiculated endoplasmic reticulum and megamitochondria with paracrystalline inclusions. There was also an associated change in the number, size, and distribution of lipid droplets in hepatocytes and fat-storing cells. Electron microscopic autoradiographic techniques were utilized to determine the cellular and subcellular distribution of 3H-3,4,3',4'-tetrachlorobiphenyl (3H-TCB) in the adult rat liver and determine if there is any relationship between subcellular morphologic change and radiolabel localization. Adult female WAG/Rij rats received a single intraperitoneal injection of 200 mg TCB/kg containing 1.85 mCi of 3H-TCB and were sacrificed at 1, 3, 7, and 14 days following exposure. The vast majority of 3H-TCB-derived radioactivity was located in the hepatocyte at all time points examined, ranging from 79-86% of the total number of autoradiographic grains counted over the liver cells. Sequential order of radiolabel localization per liver cell type at 1, 3, and 7 days was hepatocyte much greater than Kupffer cell greater than fat-storing cell greater than endothelial cell. At day 14, the sequential order of radiolabel localization per liver cell type was hepatocyte much greater than fat-storing cell greater than Kupffer cell greater than endothelial cell, which indicates that there was some shift movement of label over time. The lipid droplet, mitochondria, and endoplasmic reticulum were the subcellular structures or organelles of hepatocytes having the highest number of 3H-TCB-derived grains at all time periods examined.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:3,4,3',4'-tetrachlorobiphenyl-induced effects in the rat liver. II. Electron microscopic autoradiographic localization of 3H-TCB. 251 43

Rats were treated for 5 to 14 days with perfluoroacetate, perfluorobutyrate and perfluorooctanoate. Alterations in hepatic morphology with special reference to the peroxisomal compartment were investigated by light and electron microscopy following cytochemical staining of catalase activity with the alkaline 3,3'-diaminobenzidine medium. All three compounds induced hepatomegaly and peroxisome proliferation. Perfluorobutyrate and perfluorooctanoate were found to be more active than perfluoroacetate. Perfluorooctanoate-induced peroxisome proliferation was more prevalent in centrilobular than in periportal hepatocytes. Peroxisomes in centrilobular liver cells frequently were of round shape, exhibited diameters of up to 1.5 microns and were predominantly located within smooth endoplasmic reticulum-glycogen areas. In periportal cells, however, clusters of polymorphous peroxisomes ranging from 250 to 1,100 nm in diameter were observed at the periphery of smooth endoplasmic reticulum-glycogen regions. Peroxisome proliferation was accompanied by a change of peroxisomal and mitochondrial enzyme activities, in particular an increase in peroxisomal palmitoyl-CoA oxidation. Significant alterations in the concentration of peroxisomal matrix and membrane polypeptides were also noted. Within the first 2 days, perfluorooctanoate treatment exerted a strong hypolipidemic activity and both compounds perfluorooctanoate and perfluorobutyrate raised the level of hepatic free acid-soluble CoA nearly 10-fold as compared with control livers. The results suggest perfluorinated carboxylic acids to be model substances suitable to correlate biochemical and morphological parameters with the zonal heterogeneity of the peroxisomal compartment in rat liver. Due to the manifold hepatic effects, contact of humans with perfluorinated carboxylic acids or their metabolic precursors may represent a severe health risk.
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PMID:Biochemical effects and zonal heterogeneity of peroxisome proliferation induced by perfluorocarboxylic acids in rat liver. 292 63

Overproduction of the hepatitis B virus (HBV) large envelope polypeptide by transgenic mice containing the entire HBV envelope coding region leads to the formation of extremely long (up to 800 nm), occasionally branching, filamentous 22-nm-diameter hepatitis B surface antigen particles that accumulate within the endoplasmic reticulum of the hepatocyte and are not efficiently secreted. As the endoplasmic reticulum expands to accommodate the increasing cellular filament stores, the hepatocytes become enlarged, hydropic, and eosinophilic and also display the characteristic features of "ground-glass" cells. As filament storage progresses, the ground-glass cells undergo coagulative necrosis and the mice develop an age-dependent lesion, whose severity is related to the intracellular concentration of envelope polypeptide, that is characterized by focal hepatocellular degeneration and necrosis, lobular macrophagic inflammation, and increased serum transaminase activity. Advanced lesions demonstrate hepatocellular hyperplasia evident as lobular architectural disarray and microscopic hepatocellular nodules, many of which no longer contain detectable HBV envelope antigens. These changes may become extreme, producing a massively enlarged liver due to multifocal nodular regenerative hyperplasia. Overproduction of the large HBV envelope polypeptide exerts major structural constraints on HBV particle formation, leading to reduced secretion and progressive intracellular accumulation of hepatitis B surface antigen, which can reach sufficiently high concentrations to be directly cytotoxic to hepatocytes in this transgenic mouse system.
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PMID:Structural and pathological effects of synthesis of hepatitis B virus large envelope polypeptide in transgenic mice. 347 14

Ammonium perfluorooctanoate (APFO) is known to induce a striking hepatomegaly in rats. The purpose of these studies was to determine the causes of the hepatomegaly and compare the effect to other liver-enlarging compounds. Since the total hepatic DNA content was similar in control and APFO-treated rats, the hepatomegaly represented a hypertrophic rather than a hyperplastic response. The cytochrome P-450 content and activity of benzphetamine N-demethylase increased in the livers of APFO-treated rats, indicating the proliferation of the smooth endoplasmic reticulum. In contrast to the membrane-bound enzymes, the soluble enzymes glutathione S-transferase and UDPglucuronyltransferase were unaffected by APFO treatment. The activity of carnitine acetyltransferase was disproportionately increased relative to carnitine palmitoyltransferase in the livers of APFO vs that in control rats, confirming the predominant proliferation of peroxisomes vs that of mitochondria. Morphological studies confirmed the proliferation of the endoplasmic reticulum, mitochondria, and peroxisomes in the livers of APFO-treated rats. In contrast to many other peroxisome proliferating agents, APFO did not possess hypolipidemic activity.
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PMID:Biochemical and morphological studies of ammonium perfluorooctanoate-induced hepatomegaly and peroxisome proliferation. 360 46

Patients with chronic heart failure (CHF) can often develop such diseases as hepatitis of viral etiology, alcoholic hepatitis, drug affection of the liver and other diseases masked as congestive liver. In most cases CHF concomitant liver diseases have an atypical course with a tendency to a chronic course. CHF is one of the important pathogenetic mechanisms lying in the basis of chronicity of concomitant liver diseases. Refractory CHF, inconsistency of the hemodynamic indices of persistent hepatomegaly must lead a physician to the detection of probable independent liver diseases complicating the syndrome of heart failure. CHF is a factor causing an enhanced fibrosing liver reaction. An important diagnostic test of fibrinogenesis lying in the basis of chronicity of liver diseases, is the determination of enzymatic markers reflecting synthesis and catabolism of the main substance of connective tissue. Change in the levels of haptoglobin, ceruloplasmin and glutamic acid dehydrogenase is an indirect sign of damage of the liver parenchymal endoplasmic reticulum. These indices can serve as differential criteria of the prevalence of cardiovascular disorders in the liver or concomitant independent liver diseases.
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PMID:[Pathogenetic mechanisms of chronicity in liver diseases in patients with circulatory failure]. 361 41

The hypolipidemic activity of tiadenol-disulfoxide, the major metabolite of 1,10-bis(hydroxyethylthio)decane (tiadenol, Eulip) in man and in the rat was assessed in various experimental models versus the corresponding activity of tiadenol. Tiadenol-disulfoxide in the normolipidemic rats lowers total serum cholesterol and serum and liver triglycerides in an extent comparable to that of the reference compound. Likewise, it is equally effective as tiadenol in preventing Triton-induced hyperlipidemia and Nath diet induced hypercholesterolemia; in addition tiadenol-disulfoxide is slightly more effective than tiadenol in increasing HDL-cholesterol in hypercholesterolemic rats. At hypolipidemic doses the compound causes no hepatomegaly, no induction of peroxisomal catalase and palmitoyl-CoA oxidase activities, no smooth endoplasmic reticulum proliferation and no induction of microsomal cytochrome P-450 and of cytochrome P-450 dependent enzyme activities: aminopyrine (aminophenazone) N-demethylase, aniline hydroxylase, zoxazolamine hydroxylase and hexobarbital oxidase. At the suprapharmacological dose of 300 mg/kg tiadenol-disulfoxide, if compared to the reference compound, shows a generally lower order of toxicity on these hepatic parameters. Orally administered tiadenol-disulfoxide is well absorbed by the gastrointestinal tract and is eliminated in urine at 45% of the dose in unchanged form, and the remaining being: glucuron-conjugated tiadenol-disulfoxide (10%), S-oxidized metabolites (15%) and sulfoxidized carboxylic metabolites (15%). The compound is well tolerated both in mice and rats. The results of this comparative study demonstrate that: 1. tiadenol-disulfoxide is a substance with promising hypolipidemic properties; 2. tiadenol-disulfoxide is largely responsible for the hypolipidemic activity of tiadenol; 3. hepatomegaly consequent to tiadenol administration is the consequence of the response of the liver cell to the increased functional demand of the mixed function oxidase (MFO) system involved in the metabolism of the drug; 4. peroxisomal enzyme activities induction observed with both drugs at non-pharmacological doses does not play any role in their hypolipidemic action and is not associated with hepatomegaly.
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PMID:Experimental studies on pharmacology, metabolism and toxicology with tiadenol-disulfoxide. Dissociation of lipid lowering effects and the induction of peroxisomal and microsomal drug-metabolizing enzymes. 366 66

In rats, the liver is the primary target organ of perfluoro-n-decanoic acid (PFDA) toxicity. Therefore, the effects of PFDA on hepatic ultrastructure were studied in rats. Pathological changes induced by PFDA in hamsters, mice, and guinea pigs were also examined. PFDA caused a severe reduction in body weight in all four species studied. A reduction in food intake was observed in rats and hamsters. However, hamsters continued to consume food at a reduced level, while rats stopped eating for a 5- to 6-day period about 6 days after dosing. The PFDA-induced pathological changes in the hamsters, mice, and guinea pigs resembled those seen in rats to varying degrees. As in the rat, PFDA caused a marked liver enlargement in mice and hamsters and a moderate swelling in guinea pigs. This hepatomegaly was ascribed primarily to individual cell swelling. Thymic atrophy was noted in PFDA-treated hamsters, mice, and guinea pigs. Seminiferous tubular degeneration observed in hamsters and guinea pigs, but not in mice, was not as severe as in the rat, where in some cases frank necrosis has been seen. Ultrastructural changes in the livers of all PFDA-treated animals, regardless of species, included disruption of the rough endoplasmic reticulum, rounding and swelling of the mitochondria with related structural alterations, and mild to extensive proliferation of peroxisomes. This peroxisome proliferative response was greatest in mice and almost absent in guinea pigs. Accumulation of lipid droplets in liver cells due to PFDA treatment was more pronounced in hamsters and guinea pigs than in rats and mice. PFDA-induced hepatomegaly with a concomitant increase in peroxisomes in several rodent species may be associated with an impairment of normal lipid metabolism in the liver by PFDA.
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PMID:Pathological and hepatic ultrastructural effects of a single dose of perfluoro-n-decanoic acid in the rat, hamster, mouse, and guinea pig. 369 11

Fifteen male mice (C57/Bl6J) were fed the liquid diet "Stardit" supplemented with vitamins together with phenytoin for 8 weeks; experimental animals and controls were pair-fed. After 8 weeks of treatment, the anesthetized animals were perfused with 3.5% glutaraldehyde. Tissue samples of the cerebral cortex (area 3), cerebellum (vermis), thalamus, hypothalamus, and liver were embedded in Araldite. All phenytoin-treated animals displayed a hepatomegaly. Semithin sections and ultrastructural investigations of the cerebellar vermis showed pyknoses of granule cells and an enlargement and swelling of parallel fibers in presynaptic areas in the molecular layer. The swollen axons showed an accumulation of tubular structures which represented proliferated smooth endoplasmic reticulum. Similar tubular structures were observed in hepatocytes of experimental animals. It is proposed that phenytoin caused an induction of the microsomal system of hepatocytes and granule cells which led to a proliferation of the smooth endoplasmic reticulum. The transport of these organelles to the axon terminals of parallel fibers via the axoplasmic flow is assumed to cause a swelling of the presynaptic area. A dying-back process may then lead to pyknosis of granule cells. Chronic phenytoin administration to mice is a new experimental model of neuroaxonal dystrophy.
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PMID:Degeneration of granule cells following chronic phenytoin administration: an electron microscopic investigation of the mouse cerebellum. 394 Aug 80

This study compares changes in the livers of rats treated with di(2-ethylhexyl) phthalate (DEHP) and its straight-chain analogs di(n-hexyl) phthalate (DnHP) and di(n-octyl phthalate (DnOP). Groups of rats were fed diets containing 20,000 ppm of one of these compounds. Subgroups were killed after 3, 10, and 21 days, and the livers were examined by histological, cytological, and biochemical methods. The results show considerable differences between the effects of the branched-chain phthalate ester DEHP and its straight-chain analogs. The major effects on the liver following administration of diets containing DEHP were midzonal and periportal accumulation of small droplets of lipid, hepatomegaly accompanied by an initial burst of mitosis, proliferation of hepatic peroxisomes and of smooth endoplasmic reticulum accompanied by induction of peroxisomal fatty acid oxidation, damage to the peroxisomal membranes as evidenced by increased leakage of catalase to the cytosol, and centrilobular loss of glycogen and falls in glucose-6-phosphatase activity and in low-molecular-weight reducing agents. In contrast, diets containing DnHP or DnOP induced accumulation of large droplets of fat around central veins leading, by 10 days, to mild centrilobular necrosis and a very slight induction of one peroxisomal enzyme and an increase in liver weight, but no significant changes in any other parameters which were affected by DEHP.
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PMID:Comparison of the short-term effects of di(2-ethylhexyl) phthalate, di(n-hexyl) phthalate, and di(n-octyl) phthalate in rats. 396 35

Low activity of phosphorylase and increased concentration of glycogen were found in liver tissue from five children with asymptomatic hepatomegaly. In vitro activation of liver phosphorylase in these patients occurred at the rate of 10% or less of normal. Elimination of the defect by the addition of kinase that activates phosphorylase demonstrated the integrity of the phosphorylase enzyme and the deficient activity of dephophophosphorylase kinase. On the average, 60% of the phosphorylase enzyme of normal human liver was in the active form. Phosphorylase kinase of rabbit muscle activated phosphorylase of normal human liver to a final value that was significantly higher than the one obtained in the absence of muscle phosphorylase kinase. The ultrastructural examination of hepatic tissue from the five patients revealed increased amounts of glycogen. There was scarcity of endoplasmic reticulum. There was intercellular glycogen in continuity with the glycogen of the hepatocytes through breaks in their circumference. Lipid droplets with lucid areas in the form of needles and plates contained aggregates of glycogen. There were numerous lysosomes, some containing glycogen. Large vacuoles filled with glycogen and surrounded by a membrane were seen occasionally. The vacuoles might reflect the lysosomal pathway of glycogen degradation, since there was apparent fusion of such autophagic vacuoles with small vesicles resembling primary lysosomes.
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PMID:Deficient activity of dephosphophosphorylase kinase and accumulation of glycogen in the liver. 577 8


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