Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MRP3 is an ABC transporter localized in the basolateral membrane of epithelial cells such as hepatocytes and enterocytes. In this study, the role of Mrp3 in drug disposition was investigated. Because Mrp3 preferentially transports glucuronide conjugates, we investigated the in vivo disposition of acetaminophen (APAP) and its metabolites. Mrp3+/+ and Mrp3-/- knockout mice received APAP (150 mg/kg), and bile was collected. Basolateral and canalicular excretion of APAP was also assessed in the isolated perfused liver. In separate studies, mice received 400 mg APAP/kg for assessment of hepatotoxicity. No differences were found in the biliary excretion of APAP, APAP-sulfate, and APAP-glutathione between Mrp3+/+ and Mrp3-/- mice. However, 20-fold higher accumulation of APAP-glucuronide (APAP-GLUC) was found in the liver of Mrp3-/- mice. Concomitantly, plasma APAP-GLUC content in Mrp3-/- mice was less than 10% of that in Mrp3+/+ mice. In addition, APAP-GLUC excretion in bile of Mrp3-/- mice was tenfold higher than in Mrp3+/+ mice. In the isolated perfused liver, we also found a strong decrease of APAP-GLUC secretion into the perfusate of Mrp3-/- livers. Plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), and histopathology showed that Mrp3-/- mice are more resistant to APAP hepatotoxicity than Mrp3+/+ mice, which is most likely a result of the faster repletion of hepatic GSH. In conclusion, basolateral excretion of APAP-GLUC in mice is nearly completely dependent on the function of Mrp3. In its absence, sufficient hepatic accumulation occurs to redirect some of the APAP-GLUC to bile. This altered disposition in Mrp3-/- mice is associated with reduced hepatotoxicity.
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PMID:Altered disposition of acetaminophen in mice with a disruption of the Mrp3 gene. 1625 50

This study explores the morpho-structure of gallstones (GSs) removed from 36 patients in NW Romania and correlate it with the laboratory results of the patients. GSs were analyzed by SEM-EDS, X-ray diffraction and IR, UV-Vis and X-ray photoelectron spectroscopy. The laboratory studies consisted in hematological, coagulation, biochemistry, immunological and tumor markers tests. The morphological and structural investigations allowed to classify the GS in five different types and to establish their mechanism of formation. Only macroscopic evaluation, SEM microscopy, FTIR and UV-Vis spectroscopy give different easily noticeable information for each GS type. EDS, XPS and XRD diffraction are recommended to distinguish pigment and carbonate stones from the other GS types and a carefully examination is needed to establish the differences between the pure cholesterol, the mixed cholesterol and the composite cholesterol stones, due to the high similarities. The variation of specific markers cannot differentiate the patients with pure cholesterol GS from those with mixed cholesterol and pigment GS and those with mixed cholesterol from those with composite cholesterol stones. Seven laboratory parameters (RDW-CV, MPV, PCT, GLUC-HK, WBC, PT, GPT) are the key indicators for the GS disease and trend to present generally higher values than normal.
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PMID:Multi-analyses of gallstones and correlation between their properties with the laboratory results. 3197 57