Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

CD-1 mice were given oral doses of 0-16 ml/kg/day for five days of Prudhoe Bay (PBCO), South Louisiana and Arabian Light crude oils, Bunker C oil (BCO), mineral oil (MO) and corn oil. Minor decreases in packed cell volume and increases in mean corpuscular hemoglobin concentration occurred after ingestion of crude oils and BCO. Dietary depletion of vitamin E and selenium failed to enhance hematological changes. Pronounced liver enlargement and atrophy of thymus and spleen accompanied ingestion of all petroleum oils except MO and were shown to be dependent on dose of PBCO. Concentration of RNA and total RNA were increased while total DNA, but not concentration of DNA, was increased in enlarged livers. Liver enlargement was attributed primarily to hyperplasia with an additional contribution due to hypertrophy. The severe hemolytic anemia reported in marine birds that ingested PBCO was not reproduced in mice. Liver enlargement and lymphoid tissue atrophy were similar to those reported in other species exposed to petroleum oils.
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PMID:The systemic toxicity of Prudhoe Bay Crude and other petroleum oils to CD-1 mice. 169 Sep 73

Peroxisomeproliferators (PPs) cause hepatomegaly, peroxisome proliferation, and hepatocarcinogenesis in rats and mice. Conversely, hamsters are less responsive to these compounds. PPs increase peroxisomal beta-oxidation and P4504A subfamily activity, which has been hypothesized to result in oxidative stress. We hypothesized that differential modulation of glutathione-related defenses could account for the resulting difference in species susceptibility following PP administration. Accordingly, we measured glutathione S-transferase (GST), glutathione peroxidase (GPx), and glutathione reductase (GR) activities, and total glutathione (GSH) in male Sprague-Dawley rats and Syrian hamsters fed two doses of three known peroxisome proliferators [dibutylphthalate (DBP), gemfibrozil, and Wy-14,643] for 6, 34, or 90 days. In rats, decreases in GR, GST, and selenium-dependent GPx were observed following PP treatment at various time points. In hamsters, we observed higher basal levels of activities for GR, GST, and selenium-dependent GPx compared to rats. In addition, hamsters showed decreases in GR and GST activities following PP treatment. Interestingly, selenium-dependent GPx activity was increased in hamsters following treatment with Wy-14,643 and DBP. Treatment for 90 days with Wy-14,643 resulted in no change in GPx1 mRNA in rats and increased GPx1 mRNA in hamsters. Sporadic changes in total GSH and selenium-independent GPx were observed in both species. This divergence in the hydrogen peroxide detoxification ability between rats and hamsters could be a contributing factor in the proposed oxidative stress mechanism of PPs observed in responsive and nonresponsive species.
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PMID:Effects of peroxisome proliferators on glutathione and glutathione-related enzymes in rats and hamsters. 1118 Nov 9

Zrt/Irt-like protein 8 (ZIP8) (encoded by Slc39a8) is a multifunctional membrane transporter that influxes essential metal cations Zn²⁺, Mn²⁺, Fe²⁺, and nonmetal inorganic selenite (HSeO₃^-). Physiological roles of ZIP8 in different cell types and tissues remain to be elucidated. We aimed to investigate ZIP8 functions in liver. Two mouse models were used in this study: 1) 13- to 21-mo-old Slc39a8(+/neo) hypomorphs having diminished ZIP8 levels and 2) a liver-specific ZIP8 acute knockdown mouse (Ad-shZip8). Histology, immunohistochemistry, and Western blotting were used to investigate ZIP8-deficiency effects on hepatic injury, inflammatory changes, and oxidative stress. Selenium (Se) and zinc (Zn) were quantified in tissues by inductively coupled plasma-mass spectrophotometry. We found that ZIP8 is required to maintain normal liver function; moderate or acute decreases in ZIP8 activity resulted in hepatic pathology. Spontaneous liver neoplastic nodules appeared in ~50% of Slc39a8(+/neo) between 13 and 21 mo of age, exhibiting features of inflammation, fibrosis, and liver injury. In Ad-shZip8 mice, significant hepatomegaly was observed; histology showed ZIP8 deficiency was associated with hepatocyte injury, inflammation, and proliferation. Significant decreases in Se, but not Zn, were found in Ad-shZip8 liver. Consistent with this Se deficit, liver expression of selenoproteins glutathione peroxidases 1 and 2 was downregulated, along with decreases in antioxidant superoxide dismutases 1 and 2, consistent with increased oxidative stress. Thus, ZIP8 plays an important role in maintaining normal hepatic function, likely through regulating Se homeostasis and redox balance. Hepatic ZIP8 deficiency is associated with liver pathology, including oxidative stress, inflammation, proliferation, and hepatocellular injury. NEW & NOTEWORTHY Zrt/Irt-like protein 8 (ZIP8) is a multifunctional membrane transporter that facilitates biometal and mineral uptake. The role of ZIP8 in liver physiology has not been previously investigated. Liu et al. discovered unique ZIP8 functions, i.e., regulation of hepatic selenium content and association of ZIP8 deficiency in mouse liver with liver defects.
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PMID:Hepatic ZIP8 deficiency is associated with disrupted selenium homeostasis, liver pathology, and tumor formation. 3044 45

Selenoneine is a novel organic selenium compound markedly found in the blood, muscles, and other tissues of fish. This study aimed to determine whether selenoneine attenuates hepatocellular injury and hepatic steatosis in a mouse model of non-alcoholic fatty liver disease (NAFLD). Mice lacking farnesoid X receptor (FXR) were used as a model for fatty liver disease, because they exhibited hepatomegaly, hepatic steatosis, and hepatic inflammation. Fxr-null mice were fed a 0.3 mg Se/kg selenoneine-containing diet for four months. Significant decreases in the levels of hepatomegaly, hepatic damage-associated diagnostic markers, hepatic triglycerides, and total bile acids were found in Fxr-null mice fed with a selenoneine-rich diet. Hepatic and blood clot total selenium concentrations were 1.7 and 1.9 times higher in the selenoneine group than in the control group. A marked accumulation of selenoneine was found in the liver and blood clot of the selenoneine group. The expression levels of oxidative stress-related genes (heme oxygenase 1 (Hmox1), glutathione S-transferase alpha 1 (Gsta1), and Gsta2), fatty acid synthetic genes (stearoyl CoA desaturase 1(Scd1) and acetyl-CoA carboxylase 1 (Acc1)), and selenoprotein (glutathione peroxidase 1 (Gpx1) and selenoprotein P (Selenop)) were significantly decreased in the selenoneine group. These results suggest that selenoneine attenuates hepatic steatosis and hepatocellular injury in an NAFLD mouse model.
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PMID:Selenoneine Ameliorates Hepatocellular Injury and Hepatic Steatosis in a Mouse Model of NAFLD. 3260 60

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