ABSTRACT
The intensity of (75)Se transport in the predominant direction after intraperitoneal injection of [(75)Se]selenate was compared in 1- and 3-month-old rats receiving common vivarium ration or sucrose diet. The incorporation percent, blood/liver relative radioactivity, and relative radioactivity difference coefficient were evaluated in the blood and liver. The dynamics of label incorporation in the blood of rats fed common diets has two peaks (at 1-3 h and 12-24 h) and a drop at 6 h. Coefficient of difference in 1-month-old rats was characterized by a greater amplitude of fluctuations than in 3-month-old animals.
Subject(s)
Liver/metabolism , Selenium Radioisotopes/blood , Selenium Radioisotopes/pharmacokinetics , Age Factors , Animals , Biological Transport/physiology , Rats , Selenium Radioisotopes/metabolism , Time FactorsABSTRACT
The effect of cholestasis on ileal bile acid absorption is controversial in animal models (up- or down-regulation) and unknown in humans. We therefore studied values of the selena homotaurocholic acid (SeHCAT) test before and after long-term administration (>3 months, 13-15 mg/kg/day) of ursodeoxycholic acid (UDCA) in 27 patients with chronic cholestatic liver diseases (24 women, 3 men; mean age, 50 years; 24 primary biliary cirrhosis, 2 secondary biliary cirrhosis, 2 others). The control group consisted of 14 healthy volunteers. Seven-day SeHCAT percentage retention was identical in the 12 untreated cholestatic patients (serum bilirubin, 75+/-42 micromol/L, alkaline phosphatase, 4.2+/-1.0 N; mean+/-SEM) and in the control group (43.6+/-2.9 and 43.8+/-4.2%, respectively). In the 22 patients treated by UDCA for 38+/-8 months, SeHCAT percentage retention was 20.3+/-3.0%. In the seven patients with the SeHCAT test done before and after UDCA treatment (16+/-5 months), SeHCAT percentage retention decreased significantly under UDCA therapy (42.0+/-4.4 vs 19.4+/-4.1%; P < 0.02). We conclude that, in patients with chronic cholestasis (1) SeHCAT percentage retention is not altered-taken together with the known defect of biliary excretion, this lack of increase in SeHCAT percentage retention argues against up-regulation of bile acid ileal transport; and (2) UDCA treatment induces a decrease in the SeHCAT percentage retention-this effect may be related primarily to a decreased bile acid ileal absorption.
Subject(s)
Bile Acids and Salts/metabolism , Cholestasis/metabolism , Ileum/metabolism , Selenium Radioisotopes/blood , Taurocholic Acid/analogs & derivatives , Ursodeoxycholic Acid/therapeutic use , Alkaline Phosphatase/metabolism , Cholestasis/complications , Cholestasis/drug therapy , Chronic Disease , Down-Regulation , Female , Humans , Intestinal Absorption , Liver Cirrhosis/complications , Male , Middle Aged , Taurocholic Acid/blood , Up-Regulation , gamma-Glutamyltransferase/metabolismABSTRACT
Three Se-deficient and three Se-sufficient sheep with mean erythrocyte glutathione peroxidase activities of 30 and 249 mumol NADPH oxidized.min-1.g hemoglobin-1, respectively, were each labeled intraperitoneally with 555 MBq of sodium [75Se]selenite. All animals were killed and necropsied after 7 d. Peak plasma radioactivity occurred from 1 to 3 h post-labeling. Radioactivity in plasma associated with [75Se]selenoproteins was significantly higher in the Se-deficient sheep than in the Se-sufficient sheep 3 and 6 d after isotope administration. SDS-PAGE analysis of plasma followed by autoradiography indicated five selenoproteins, all of which were present in both groups. The molecular weights were 21.0, 23.0, 48.0, 55.5 and > 100 kDa. The protein with a mass of 55.5 kDa accounted for > 40% of the total radioactivity in both groups of sheep. Nine selenoproteins with molecular weights of 15.7, 18.8, 22.9, 26.8, 37.3, 42.4, 56.1, 62.7 and 71.3 kDa were detected in extracts from a range of tissues. Liver, kidney, heart and pituitary retained more radioactivity than the other tissues examined and the total amount of protein-associated 75Se in the liver, kidney and pituitary of Se-deficient sheep was significantly greater than that in Se-sufficient controls.