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In situ intestinal absorption of 2-chloro-N-isopropylacetanilide (propachlor) and non-biliary excretion of metabolites into the intestinal tract of rats, pigs and chickens.

1. Propachlor was absorbed from in situ intestinal loops of rats and pigs, with absorption half-times of 7.5 and 16.5 min, respectively. 2. Water-soluble 14C-labelled metabolites that accumulated in the intestinal loops accounted for 31%, 53%, and 25% of the starting 14C for rats, pigs and chickens, respectively. 3. Propachlor(S)cysteine was identified as the major metabolite in the pig intestinal lumen (43% of the water-soluble 14C). 4. It is concluded that intestinal metabolism and intestinal excretion of water-soluble metabolites of propachlor are important physiological processes that occur in a variety of animal species. These processes provide a route by which metabolites of xenobiotics may reach the intestinal lumen in animals which are poor biliary excretors.

Acetanilides↗

Cytoskeleton involvement on intestinal absorption processes.

It has been recently demonstrated in the laboratory that the cytoskeletal inhibitor cytochalasin E has an indirect inhibitory effect on the function of the intestinal Na+-sugar cotransporter (SGLT1). The present work confirms that cytochalasin E inhibits SGLT1 activity through cytoskeleton disruption, showing that in anaerobic conditions (N2 bubbling), which implies low cytosolic ATP levels, the inhibition is not observed. As it occurs in sugar transport, the Na+-dependent intestinal transport of phenylalanine decreases if cytochalasin E is present in the incubation medium. However, the activity of the brush border enzymes sucrase, amino peptidase N and gamma-glutamyl transferase is not affected by the inhibitor. These enzymes only have one transmembrane domain and the active center is projected to the intestinal lumen. Therefore, cytoskeleton changes that could modify the transmembrane enzyme segment do not alter the activity of these enzymes. Examination of the intestine morphology after 30 min incubation with cytochalasin E shows only light modifications which do not seem to explain the inhibitory effects of the toxin on Na+-sugar or Na+-phenylalanine cotransporters function. On the whole, these results indicate that the inhibition of cytochalasin E on galactose and phenylalanine intestinal transport is secondary to its action on cytoskeleton through protein structure modifications.

Animals↗

Intestinal absorption and lymphatic transport of peroxidized lipids in rats: effect of exogenous GSH.

We previously found that mucosal glutathione (GSH) plays an important role in the intestinal metabolism of luminal peroxidized lipids [T. Y. Aw, M. W. Williams, and L. Gray. Am. J. Physiol. 262 (Gastrointest. Liver Physiol. 25): G99-G106, 1992]. To determine the effects of exogenous GSH on lipid hydroperoxide elimination under conditions in which mucosal GSH was initially depleted with buthionine sulfoximine (BSO), we infused peroxidized lipid solutions without or with GSH into the proximal intestine of rats and monitored the steady-state output of hydroperoxides in lymph and recovery of luminal hydroperoxides. GSH supplementation in BSO-treated rats resulted in a concentration-dependent attenuation of lymphatic output of peroxidized lipids that was correlated with increases in mucosal GSH. Compared with BSO control, the luminal lipid hydroperoxide contents were significantly lower in GSH-supplemented rats, consistent with enhanced elimination of peroxidized lipids by exogenous GSH. The effect of GSH was ameliorated by the inhibitors of GSH uptake, suggesting that the uptake of GSH is required for promotion of intestinal removal of luminal hydroperoxides. Other thiols, either at comparable or higher concentrations than GSH, were without significant effects on lymphatic transport or luminal recovery of lipid hydroperoxides, indicating that these thiols are poor substitutes for GSH. Overall, the data are consistent with exogenous GSH being a source for cellular reduction of peroxidized lipids. Results from these studies could directly impact on future consideration of therapeutic means to increase cellular antioxidant systems to promote intestinal hydroperoxide detoxication.

Animals↗

[Intestinal absorption of iron. Mechanism and interactions].

The mechanism and the regulation of intestinal iron absorption are described. Iron absorption is enhanced from animal foods, whereas it is reduced from vegetable foods. These data can be useful in the treatment of iron deficiency and iron overload.

Dietary Proteins↗

Intestinal absorption of proline and leucine in chronically catheterized rats.

BACKGROUND & AIMS: Most studies of intestinal amino acid absorption use methods in which intestinal function is studied immediately after surgical manipulation. The unphysiological experimental conditions present in these studies limit the ability to extrapolate their results to normal physiological conditions. The aim of this study was to determine the rates of proline and leucine absorption under normal physiological conditions. METHODS: Absorption of proline and leucine was measured in long-term catheterized rats using a method of dual infusion of radiolabeled isotopes. RESULTS: The maximum transport velocity and apparent membrane permeability for proline were 16.1 mumol/ min and 0.07 mumol.min-1.mmol/L-1. For leucine, the maximum transport velocity and apparent membrane permeability were 14.9 mumol/min and 0.08 mumol.min-1.mmol/L-1. Surgical bowel manipulation decreased the maximum transport velocities for proline and leucine by > 80%. The adverse effects of surgery were present for 24 hours. CONCLUSIONS: Under normal physiological conditions, most proline and leucine is absorbed by active transport. Measurements of amino acid absorption using methods in which the intestine has been surgically manipulated within the previous 24 hours significantly underestimate proline and leucine absorption and do not reflect absorption under normal physiological conditions.

Anesthesia↗

Drug effects on the intestinal absorption of estrogens.

It is now recognized that intestinal metabolism is one of the major factors affecting the bioavailability of orally administered, natural and synthetic estrogens. Other drugs and dietary constituents taken concomitantly may modify the intestinal metabolism and enterohepatic circulation of these steroids. Various antibiotics, phenobarbitone and large doses of ascorbic acid have been reported to modify the clinical efficacy of steroidal oral contraceptives. Experimental and other evidence indicate that antibiotics, by modifying the intestinal microflora, affect the intestinal metabolism and enterohepatic circulation of estrogens. Phenobarbitone and ascorbic acid on the other hand probably influence intestinal metabolism through an effect on intestinal mucosal enzymes. Further experimental evidence in rats suggest that such commonly used drugs as analgesic acetylsalicylic acid, antimalarial chloroquine phosphate and alcohol also alter the intestinal mucosal metabolism of estradiol and estrone sulphate and may thus alter the bioavailability of these estrogens. Further studies are necessary to evaluate the clinical significance of these observations.

Analgesics↗

Prolonged intestinal absorption of cephradine with chitosan-coated ethylcellulose microparticles in rats.

Cephradine-containing ethylcellulose microparticles (MPC) were prepared by the solvent evaporation method. Chitosan-coated MPC (Chi-MPC) were prepared by doping MPC with viscous chitosan solution and subsequently drying. When fluorescein isothiocyanate (FITC)-labeled chitosan-coated ethylcellulose microparticles without drug were administered intraduodenally, they moved slowly in the intestine, that is, most of them were retained at the upper and middle parts of the small intestine for more than 8 h, which is considered due to mucoadhesive properties of coated chitosan. When MPC and Chi-MPC was incubated at 37 degrees C in the JP 14 second fluid, pH 6.8, both released the drug slowly with similar release rates. Cephradine solution and suspension, MPC and Chi-MPC were administered intraduodenally to investigate intestinal drug absorption. Only Chi-MPC suppressed the initial plasma level and maintained the plasma concentration for a long time up to 24 h, suggesting Chi-MPC would be useful for prolonged intestinal absorption of cephradine.

Animals↗