Bioavailability of dietary glutathione: effect on plasma concentration.

Plasma glutathione (GSH) concentration in rats increased from approximately 15 to 30 microM after administration of GSH either as a liquid bolus (30 mumol) or mixed (2.5-50 mg/g) in AIN-76 semisynthetic diet. GSH concentration was maximal at 90-120 min after GSH administration and remained high for over 3 h. Administration of the amino acid precursors of GSH had little or no effect on plasma GSH values, indicating that GSH catabolism and resynthesis do not account for the increased GSH concentration seen. Inhibition of GSH synthesis and degradation by L-buthionine-[S,R]-sulfoximine and acivicin showed that the increased plasma GSH came mostly from absorption of intact GSH instead of from its metabolism. Plasma protein-bound GSH also increased after GSH administration, with a time course similar to that observed for free plasma GSH. Thus dietary GSH can be absorbed intact and results in a substantial increase in blood plasma GSH. This indicates that oral supplementation may be useful to enhance tissue availability of GSH.

Fate of dietary glutathione: disposition in the gastrointestinal tract.

Studies were performed in rats that had been fasted 24 h, fed a glutathione (GSH)-free semisynthetic diet (AIN-76), and fed the same diet supplemented with GSH. The results from the fasted rats and those fed GSH-free diet showed that the duodenum and jejunum contained 0.2-0.5 mumol of GSH/gram wet wt of luminal contents. The GSH contents of biliary juice was sufficient to maintain this amount of GSH in the intestinal lumen. Other analyses showed that cell sloughing, bacterial GSH content, and GSH secretion by epithelial cells of the jejunum were not sufficient to account for this content. GSH concentrations following consumption of a GSH-supplemented diet (5-50 mg/g AIN-76) showed a rapid increase in all regions of the small intestine and indicated that removal occurred primarily in the jejunum. However, the combined activities of brush-border gamma-glutamyltransferase and GSH uptake systems were not sufficient to remove all of the ingested GSH. Results from in situ vascular perfusions of small intestine showed that the upper jejunum is a principal site of GSH absorption. Measurements of the GSH-to-glutathione disulfide (GSSG) ratio in the lumen after ingestion of GSSG (5 mg/g diet) indicated that the upper small intestine also has a mechanism for reducing GSSG to GSH. The results therefore indicate that GSH is present in the lumen of the small intestine of rat under most if not all conditions. Although the physiological importance of luminal GSH remains unclear, it could potentially be used to detoxify reactive electrophiles in the diet or be absorbed for intracellular detoxication reactions.

Pyridoxine uptake by rat renal proximal tubular cells.

Uptake of [3H]pyridoxine by freshly isolated rat renal proximal tubular cells was temperature dependent and exhibited saturation kinetics, with estimated Kt and Vmax of 1.3 microM and 14 pmol/(10(6) cells.0.5 min), respectively. Pyridoxamine, 4'-deoxypyridoxine and 5'-deoxypyridoxal were as effective as unlabeled pyridoxine in inhibiting tracer uptake, whereas pyridoxamine-5'-phosphate, pyridoxal and 4'-pyridoxic acid had no effect, and other vitameric forms and structural analogs caused intermediate inhibition of cellular vitamin uptake. After 30 min, 88% of accumulated radioactive vitamin B-6 in cell extracts had been metabolized to phosphorylated forms and pyridoxal, which supports metabolic trapping as a mechanism responsible for the cellular accumulation observed. Initial uptake was significantly decreased in the presence of ethionine and ouabain; however, carbonylcyanide-p-trifluoromethoxyphenylhydrazone had no effect. Partial to complete substitution of NH4Cl and LiCl for NaCl had no effect, while partial substitution with RbCl caused significant dose-related inhibition of initial pyridoxine uptake. Amiloride also significantly decreased initial uptake. These data are consistent with a facilitated uptake process for pyridoxine that has substrate specificity and may be modulated by sodium-hydrogen exchange and/or pH gradient effects. Cellular uptake is followed by intracellular metabolic trapping catalyzed by pyridoxal kinase.

Biotin absorption by distal rat intestine.

We used the in vivo intestinal loop approach, with short (10-min) and long (3-h) incubations, to examine biotin absorption in proximal jejunum, distal ileum, cecum and proximal colon. In short-term studies, luminal biotin disappearance from rat ileum was about half that observed in the jejunum, whereas absorption by proximal colon was about 12% of that in the jejunum. In 3-h closed-loop studies, the absorption of 1.0 microM biotin varied regionally. Biotin absorption was nearly complete in the small intestine after 3 h; however, only about 15% of the dose had been absorbed in the cecum and 27% in the proximal colon after 3 h. Independent of site of administration, the major fraction of absorbed biotin was recovered in the liver; measurable amounts of radioactive biotin were also present in kidney and plasma. The results support the potential nutritional significance for the rat of biotin synthesized by bacteria in the distal intestine, by demonstrating directly an absorptive capability of mammalian large bowel for this vitamin.

Intestinal absorption of biotin in the rat.

We examined the absorption of biotin using the in vivo intestinal loop technique. Jejunal segments from male rats were filled with solutions containing [3H]biotin and [14C]inulin in Krebs-Ringer phosphate buffer, pH 6.5. Absorption was determined on the basis of luminal tritium disappearance after correction for inulin recovery. At biotin concentrations of 0.1 and 5.0 microM, luminal biotin disappearance was linear for at least 10 min. At biotin concentrations ranging from 2.3 nM to 75 microM, 10-28% of the administered dose was absorbed in 10 min. The concentration dependence of luminal biotin disappearance is consistent with the presence of both saturable and nonsaturable (linear) components of biotin uptake, with estimated Km = 9.6 microM and Jmax = 75.2 pmol/(2.5 cm loop X min). The rate constant for nonsaturable uptake is 3.1 pmol/(2.5 cm loop X min X microM). We conclude that at biotin concentrations less than 5 microM, biotin absorption proceeds largely by the saturable process, whereas at concentrations above 25 microM, nonsaturable uptake predominates. Additional studies demonstrated significantly less biotin uptake in the ileum than in the jejunum, a finding in agreement with previous in vitro studies.

Impact of intestinal parasites on digestive function in humans.

In humans as well as in animals, intestinal parasites can affect key stages of alimentation, digestion, and absorption. Selected examples of the effects of parasitic infection on food intake, intestinal propulsion and motility, organ function, epithelial structure and function, and intestinal circulation are presented. Malabsorption and nutrient loss can result from many of these common infections. Additional data are needed to determine the extent to which alterations in gastrointestinal structure and function vs. effects on appetite mediate the effects of parasites on host nutrition in humans.

Stability of thiamin in parenteral nutrition solutions.

Since the vitamin thiamin is sensitive to degradation in the presence of stoichiometric concentrations of sulfite ions, the stability of thiamin in parenteral nutrition solutions containing sulfite as an antioxidant and preservative has been questioned. The usual clinical practice of mixing amino acids, dextrose, and other solutions for administration in total parenteral nutrition significantly dilutes the concentration of sulfite. We have measured the thiamin concentration in total parenteral nutrition solutions sampled from containers after administration to patients. We have also determined the time course of thiamin degradation in solutions containing two concentrations of sulfite. Thiamin content exceeded labeled amounts in total parenteral nutrition bags containing amino acid, dextrose, and multivitamin solutions. However, when multivitamins were added directly to amino acid solutions containing 0.1% (9.6 mM) sulfite, significant degradation occurred by 5 hr. Thiamin was stable for at least 22 hr when added to total parenteral nutrition solutions containing less than 0.05% (4.8 mM) sulfite.

Folate nutrition in the elderly.

The consensus of this panel is that average dietary intake of folate in the free-living elderly population is probably adequate in most. Certainly more good data are needed; in addition, safe and reasonable dietary goals for folate intake are required. However, patients who have diseases requiring hospitalization or conditions for which institutionalization are required are obviously at greater risk. In addition, there is some evidence that the elderly poor in the US may be at greater risk of deficiency. Similarly, the evidence for folate deficiency based on blood assay data would seem to focus on the lower socioeconomic (largely Black and Hispanic) populations in addition to the hospitalized and institutionalized elderly. An additional factor in the genesis of folate deficiency among the aged is the factor of alcohol use which probably represents the single most important risk factor in folate deficiency among the elderly as well as among the nonelderly population. Although certain drugs such as anticonvulsants and sulfasalazine, may interfere with folate absorption or utilization, the number of elderly patients who are taking these drugs is relatively small and therefore this factor is not considered to be a major contributor to the problem of folate deficiency in the elderly. The question of folate malabsorption in the elderly has been examined. It is our conclusion that disease in the elderly population including gastric surgery and intestinal malabsorption, etc can certainly interfere with folate absorption but these problems are not widespread among the elderly population. There is only limited evidence that the physiological process of aging influences the intestinal absorption of folate.(ABSTRACT TRUNCATED AT 250 WORDS)

Intestinal physiology and parasitic diseases.

This paper reviews the major steps in alimentation, digestion, and absorption, which must be intact as a basis for normal nutrition, and discusses evidence relating parasitic infection in humans to effects on intestinal physiology. Parasites, with their ability to induce systemic toxicity and fever, to release active and toxic substances into the intestinal lumen, to compete for certain nutrients, to cause both functional and structural changes in the intestinal mucosa, and to stimulate hypermotility, which lessens the time available for digestion and absorption, can influence the alimentary process a almost every one of its steps. However, parasitic infection is likely to exert its most important impact at the very first step of the alimentary process, by adversely affecting the intake of food through any of a variety of mechanisms.