Transferrin stimulates iron absorption, exocytosis, and secretion in cultured intestinal cells.
(41/5177)
The cellular mechanism by which basolateral transferrin (Tf) produces an increase in apical-to-basolateral Fe flux in Caco-2 cells was analyzed. After a pulse of 59Fe from the apical medium, three types of basolateral 59Fe efflux were found: a 59Fe efflux that was independent of the presence of Tf in the basolateral medium, a 59Fe efflux in which 59Fe left the cell bound to Tf, and a Tf-dependent 59Fe efflux in which 59Fe came off the cell not bound to Tf. Furthermore, addition of Tf to the basolateral medium doubled the exocytosis rate of Tf and increased the secretion of apolipoprotein A, a basolateral secretion marker. Both apotransferrin and Fe-containing Tf produced similar increases in 59Fe efflux, Tf exocytosis, and apolipoprotein A secretion. The Ca2+ channel inhibitor SKF-96365 inhibited both the Tf-mediated increase in transepithelial Fe transport and the secretion of apolipoprotein A. Thus the activation of transepithelial Fe transport by Tf seems to be mediated by Ca2+ entry into the cells. (+info)
Genetic differences in cholesterol absorption in 129/Sv and C57BL/6 mice: effect on cholesterol responsiveness.
(42/5177)
This study compared the cholesterolemic response of two strains of mice with genetically determined differences in cholesterol absorption. When fed a basal low-cholesterol diet, 129/Sv mice absorbed cholesterol twice as efficiently as did C57BL/6 mice (44% vs. 20%). Total lipid absorption, in contrast, averaged 80-82% in both strains. The higher level of cholesterol absorption in the 129/Sv animals was reflected in an adaptive reduction in hepatic and intestinal sterol synthesis. When fed lipid-enriched diets, the 129/Sv mice became significantly more hypercholesterolemic and had twofold higher hepatic cholesterol concentrations than did the C57BL/6 animals even though the conversion of cholesterol to bile acids was stimulated equally in both strains. The difference in cholesterol absorption between these mouse strains was not the result of physicochemical factors relating to the size and composition of the intestinal bile acid pool but more likely reflects an inherited difference in one or more of the biochemical steps that facilitate the translocation of sterol across the epithelial cell. (+info)
Splanchnic and leg substrate exchange after ingestion of a natural mixed meal in humans.
(43/5177)
The disposal of a mixed meal was examined in 11 male subjects by multiple (splanchnic and femoral) catheterization combined with double-isotope technique (intravenous [2-3H]glucose plus oral U-[14C]starch). Glucose kinetics and organ substrate balance were measured basally and for 5 h after eating pizza (600 kcal) containing carbohydrates 75 g as starch, proteins 37 g, and lipids 17 g. The portal appearance of ingested carbohydrate was maximal (1.0 mmol/min) between 30 and 60 min after the meal and gradually declined thereafter, but was still incomplete at 300 min (0.46+/-0.08 mmol/min). The total amount of glucose absorbed by the gut over the 5 h of the study was 247+/-26 mmol (45+/-6 g), corresponding to 60+/-6% of the ingested starch. Net splanchnic glucose balance (-6.7+/-0.5 micromol x kg(-1) x min(-1), basal) rose by 250-300% between 30 and 60 min and then returned to baseline. Hepatic glucose production (HGP) was suppressed slightly and only tardily in response to meal ingestion (approximately 30% between 120 and 300 min). Splanchnic glucose uptake (3.7+/-0.6 micromol x kg(-1) x min(-1), basal) peaked to 9.8+/-2.0 micromol x kg(-1) x min(-1) (P<0.001) at 120 min and then returned slowly to baseline. Leg glucose uptake (34+/-5 micromol x leg(-1) x min(-1), basal) rose to 151+/-29 micromol x leg(-1) x min(-1) at 30 min (P<0.001) and remained above baseline until the end of the study, despite no increase in leg blood flow. The total amount of glucose taken up by the splanchnic area and total muscle mass was 161+/-16 mmol (29+/-3 g) and 128 mmol (23 g), respectively, which represent 39 and 30% of the ingested starch. Arterial blood lactate increased by 30% after meal ingestion. Net splanchnic lactate balance switched from a basal net uptake (3.2+/-0.6 micromol kg(-1) x min(-1) to a net output between 60 and 120 min and tended to zero thereafter. Leg lactate release (25+/-11 micromol x leg(-1) x min(-1), basal) drastically decreased postprandially. Arterial concentration of both branched-chain amino acids (BCAA) and non-branched-chain amino acids (N-BCAA) increased significantly after meal ingestion (P<0.001). The splanchnic area switched from a basal net amino acid uptake (31+/-16 and 92+/-48 micromol/min for BCAA and N-BCAA, respectively) to a net amino acid release postprandially. The net splanchnic amino acid release over 5 h was 11.3+/-4.2 mmol for BCAA and 37.8+/-9.7 mmol for N-BCAA. Basally, the net leg balance of BCAA was neutral (-3+/-5 micromol x leg(-1) x min(-1)), whereas that of N-BCAA indicated a net release (54+/-14 micromol x leg(-1) x min(-1)). After meal ingestion, there was a net leg uptake of BCAA (20+/-6 micromol x leg(-1) x min(-1)), whereas leg release of N-BCAA decreased by 50%. It is concluded that in human subjects, 1) the absorption of a natural mixed meal is still incomplete at 5 h after ingestion; 2) HGP is only marginally and tardily inhibited; 3) splanchnic and peripheral tissues contribute to the disposal of meal carbohydrate to approximately the same extent; 4) the splanchnic area transfers >30% of the ingested proteins to the systemic circulation; and 5) after meal ingestion, skeletal muscle takes up BCAA to replenish muscle protein stores. (+info)
L-aspartate of erythromycin A cyclic 11,12-carbonate, a new semisynthetic erythromycin derivative.
(44/5177)
Erythromycin A cyclic 11,12-carbonate, a compound with high antibacterial activity, forms with L-aspartic acid a salt possessing valuable properties as a potential chemotherapeutic agent. The L-aspartate of erythromycin A cyclic 11,12-carbonate exhibits strong anti-bacterial activity, especially against Gram-positive bacteria and shows low toxicity. The serum and the lung tissue levels of the discussed salt after a single dose administration to a rat were measured in comparison with those of erythromycin, its L-aspartate, erythromycin cyclic 11,12-carbonate and its L-glutamate. The new erythromycin derivative showed definitely superior characteristics to those of the other substances tested. The activity of the L-aspartate of erythromycin A cyclic 11,12-carbonate in chemotherapy of experimental staphylococcal infection and experimental pneumococcal bronchopneumonia in mice is superior to that of the parent carbonate and erythromycin itself. (+info)
Absorption and metabolism of cyanidin 3-O-beta-D-glucoside in rats.
(45/5177)
We have clarified for the first time how cyanidin 3-O-beta-D-glucoside (C3G), which is a potent antioxidant anthocyanin, is absorbed and metabolized in vivo. Rats were orally administered C3G (0.9 mmol/kg body weight), and C3G rapidly appeared in the plasma. However, the aglycon of C3G (cyanidin; Cy) was not detected, although it was present in the jejunum. Protocatechuic acid (PC), which may be produced by degradation of Cy, was present in the plasma and the concentration was 8-fold higher than that of C3G. These results suggest that plasma PC and C3G may contribute to the antioxidant activity of the plasma. In the liver and kidney, C3G was metabolized to methylated C3G (methyl-C3G), suggesting that C3G and/or methyl-C3G act as antioxidants in the tissues. (+info)
Comparative disposition of the nephrotoxicant N-(3, 5-dichlorophenyl)succinimide and the non-nephrotoxicant N-(3, 5-difluorophenyl)succinimide in Fischer 344 rats.
(46/5177)
Disposition of the nephrotoxicant N-(3,5-dichlorophenyl)succinimide (NDPS) was compared with that of a nontoxic analog, N-(3, 5-difluorophenyl)succinimide (DFPS). Male Fischer 344 rats were administered 0.2 or 0.6 mmol/kg [14C]NDPS or [14C]DFPS (i.p. in corn oil). Plasma concentrations were determined from blood samples obtained through the carotid artery. Urine samples were analyzed for metabolite content by HPLC. Rats were sacrificed at 3 h (DFPS) or 6 h (NDPS) and tissue radiolabel content and covalent binding were determined. [14C]NDPS-derived plasma radioactivity levels were 6- to 21-fold higher and peaked later than those from [14C]DFPS. Six hours after dosing, NDPS was 40% eliminated in the urine compared with approximately 90% for DFPS. By 48 h, only 67% of the NDPS dose was eliminated in urine. In contrast, DFPS excretion was virtually complete within 24 h. NDPS underwent oxidative metabolism to a slightly greater extent than DFPS. Distribution of [14C]NDPS-derived radioactivity into the kidneys was 3- to 6-fold higher than that into the liver or heart, and was more extensive than with [14C]DFPS. NDPS also covalently bound to plasma, renal, and hepatic proteins to a greater extent than DFPS. In summary, NDPS achieves higher tissue and plasma concentrations, covalently binds to a greater extent, and is eliminated more slowly than DFPS. Differences in the lipid solubility of NDPS metabolites and DFPS metabolites may help explain these results. The overall greater tissue exposure of NDPS and its metabolites may contribute to differential toxicity of these analogs. (+info)
Presystemic metabolism of albendazole: experimental evidence of an efflux process of albendazole sulfoxide to intestinal lumen.
(47/5177)
Albendazole (ABZ) presystemic clearance was studied in rat by perfusion of a 25 microM ABZ solution in isolated intestinal loops. Significant secretion of the active metabolite, ABZSO, into the lumen was observed. The metabolite was also present in mesenteric blood. After 30 min of intestinal perfusion, 64% of the ABZ dose had disappeared from lumen. The total amount of ABZSO measured was 0.341 +/- 0.04 nmol/cm with 0.176 +/- 0.03 nmol/cm in mesenteric blood. The metabolite secretion to intestinal lumen was 0.165 +/- 0.05 nmol/cm. Intestinal sulfoxidation was induced by repeated administration of ABZ and ABZ coadministered with surfactants, especially polysorbate 80. The enantioselectivity of the in vitro intestinal sulfoxidation of ABZ showed that the relative contribution of P-450 and flavin-containing monooxygenase was quite similar, but after the induction by ABZ coadministered with polysorbate 80, the cytochrome P-450 system contribution was significantly increased. The appearance of ABZSO in mesenteric blood clearance was also increased under these conditions. (+info)
Euglycemic hyperinsulinemic clamp to assess posthepatic glucose appearance after carbohydrate loading. 1. Validation in pigs.
(48/5177)
BACKGROUND: Precise knowledge of the rate of glucose absorption after meal feeding requires invasive methods in humans. OBJECTIVE: This study aimed to validate in an animal model a technique combining the euglycemic hyperinsulinemic clamp and oral carbohydrate loading (OC-Clamp) as a noninvasive procedure to quantify the posthepatic appearance of glucose after oral carbohydrate loading. DESIGN: Twenty-one pigs were fitted with arterial, jugular, portal, and duodenal catheters and a portal blood flow probe. At glucose clamp steady state, duodenal glucose (0.9 g/kg; DG-Clamp) and oral carbohydrate (140 g corn or mung bean starch as part of a mixed meal; OC-Clamp) were administered while the glucose infusion was progressively reduced to compensate for the incremental posthepatic appearance of glucose. [3-3H]glucose was used to assess the glucose turnover rate. RESULTS: Hepatic glucose production was totally suppressed by insulin infusion, and the whole-body glucose turnover rate remained stable during glucose absorption. The incremental portal appearance of glucose after the DG load was not altered by hyperinsulinemia, and the cumulative posthepatic appearance of glucose was 63 +/- 3% (x +/- SEM) of the DG load. The net hepatic portal appearance of glucose remained constant during absorption (34 +/- 3% of the load). After the OC load, the respective portal appearance rates of glucose were significantly different between carbohydrate sources; however, the rates paralleled those of the posthepatic appearance of glucose. Again, net hepatic glucose uptake expressed as portal appearance was similar for both carbohydrates. CONCLUSIONS: The results validate the OC-Clamp method to monitor the posthepatic appearance of glucose after carbohydrate ingestion and to discriminate between different carbohydrate sources. The results suggest that the technique be used in humans. (+info)