Modulation of urinary siderophores by the diet, gut microbiota and inflammation in mice.

Mammalian siderophores are believed to play a critical role in maintaining iron homeostasis. However, the properties and functions of mammalian siderophores have not been fully clarified. In this study, we have employed Chrome Azurol S (CAS) assay which is a well-established method for bacterial siderophores study, to detect and quantify mammalian siderophores in urine samples. Our study demonstrates that siderophores in urine can be altered by diet, gut microbiota and inflammation. C57BL/6 mice, fed on plant-based chow diets which contain numerous phytochemicals, have more siderophores in the urine compared to those fed on purified diets. Urinary siderophores were up-regulated in iron overload conditions, but not altered by other tested nutrients status. Further, germ-free mice displayed 50% reduced urinary siderophores, in comparison to conventional mice, indicating microbiota biotransformation is critical in generating or stimulating host metabolism to create more siderophores. Altered urinary siderophores levels during inflammation suggest that host health conditions influence systemic siderophores level. This is the first report to measure urinary siderophores as a whole, describing how siderophores levels are modulated under different physiological conditions. We believe that our study opens up a new field in mammalian siderophores research and the technique we used in a novel manner has the potential to be applied to clinical purpose.

Studies on skin and urinary mucopolysaccharides in malnourished/vitamin A deficient children.

In protein-calorie malnourished children, with or without associated vitamin A deficiency, skin content of acid mucopolysaccharides (MPS) and urinary excretion of MPS and amino sugars were studied. MPS content of skin in both malnourished groups was increased 3-6-fold. This increase was essentially in the non-sulphated component. In normal skin, non-sulphate MPS accounted for 68% of the MPS content, whereas in the malnourished group with vitamin A deficiency it constituted 93%. Urinary excretion of MPS (24h) was significantly reduced by 50-70% in malnourished groups. This returned to normal levels in the malnourished/vitamin A deficient group when vitamin A injections were administered. Excretion of amino sugars (24 h) in the malnourished groups was also decreased by 50-70%. In normal children 55% of the total amino sugars was dialysable whereas in the malnourished it was increased to 60%. The excretion of protein-bound and dialysable amino sugars was increased to normal level only in the group given supplements of vitamin A in addition of protein and calories.

Influence of vitamin A deficiency on the excretion of uromucoid and other substances in the urine of rats.

Male Fü-albino rats were weaned at the age of four weeks and maintained on a vitamin A-deficient diet. When they were 14-18 and 21-26 weeks old, the concentration of uromucoid, calcium and other substances possibly important for the pathogenesis of urinary calculi were determined. Reduced uromucoid excretion with hypercalciuria and reduced phosphate levels were observed. Subsequent examination of the kidneys did not demonstrate the presence of nephrocalcinosis or lithiasis. The relation between vitamin A, the synthesis of uromucoid and AMPS and calcium metabolism in the renal tubules is discussed.

Patterns of glycosaminoglycans excretions in the urine of Egyptians differing in their vitamin A status.

Fifty-two boys were tested biochemically for their vitamin A status. Only 54% were found to have acceptable Plasma retinol levels. Deficient vitamin A status was associated with reduced GAG excretions. Vitamin A therapy restored the plasma retinol levels and increased the excretion of GAG. Chondroitin sulfate made up 90%, heparan sulfate 9.5% and hyaluronic acid less than 1% of the total urinary GAG content.

Influence of vitamin A on formation and excretion of end products of nitrogen catabolism in chicks.

The effect of vitamin A deprivation at different stages, and of dosing with different levels of the vitamin of some parameters of protein catabolism was examined in chicks. Plasma uric acid and plasma urea were increased in vitamin A deficiency. Dosing with vitamin A caused a decrease in the plasma uric acid concentration only in deficient chicks which received the higher dosing level (3000 mug retinol equivalent), whereas plasma urea concentration increased in all cases after dosing. Nitrogen retention and uric acid excretion were not changed in chicks in the first stages of vitamin A deficiency, but excretion of urea was increased in comparison to pair fed chicks. Liver xanthine dehydrogenase (XDH) and kidney arginase were both increased even in the first stages of vitamin A deficiency. The increase in XDH activity was shown to be partially due to the stress of overnight fat caused by pair feeding, whereas this factor had no part in the increase of the kidney orginase. Dosing with vitamin A had almost no effect on the plasma vitamin A of chicks fed a high dietary level of the vitamin (9000 mug/kg) while there was a clear response in control chicks (fed 900 mug/kg) or deficient ones.

Effect of vitamin A depletion on stress-induced change in urinary output of catecholamines.

The effect of vitamin A depletion on stress-induced change in sympathoadrenal medullary activity was studied in rats. Four consecutive hours daily of immobilization provoked a marked increase in urinary excretion of free norepinephrine (NE) and epinephrine (E), confirming previous findings. The stress caused a significant decrease in output of free dopamine (DA). In contrast, the vitamin A-depleted rats in the resting state excreted threefold more NE in urine as compared with the normal animals. The urinary NE response to the stress was markedly diminished in the depleted rats, although E and DA responses to the stress were similar in magnitude to those in the normal animals. These results suggest that vitamin A depletion causes derangement of the neurosympathetic system; hence, the animals cannot appropriately respond to the stress. Alternatively, the state of vitamin A depletion may be fact a stress, and in consequence the animals have already been in a state of maximal response before immobilization.

Retinol metabolism in rats with low vitamin A status: a compartmental model.

A compartmental model was developed to describe the metabolism of vitamin A in rats with low vitamin A status maintained by a low dietary intake of vitamin A (approximately 2 micrograms retinol equivalents/day). After the IV bolus injection of [3H]retinol in its physiological transport complex, tracer and trace data were obtained from plasma, organs (liver, kidneys, small intestine, eyes, adrenals, testes, lungs, carcass), and tracer data were obtained from urine and feces. The dietary protocol developed for this study resulted in animals having plasma vitamin A levels less than 10 micrograms retinol/dl and total liver vitamin A levels of approximately 1 microgram retinol equivalent. Four compartments were used to model the plasma: one to describe retinol, one to describe the nonphysiological portion of the dose, and two to simulate polar metabolites derived from retinol. The liver required two compartments and a delay, the carcass (small intestine, eyes, adrenals, testes, and lungs, plus remaining carcass) required three compartments, and the kidneys required two. The model predicted a vitamin A utilization rate of 1.65 micrograms retinol equivalents/day with the urine and feces accounting for most of the output. The plasma retinol turnover rate was approximately 20 micrograms retinol equivalents/day; this was 12 times greater than the utilization rate. This indicated that, of the large amount of retinol moving through the plasma each day, less than 10% of this was actually being irreversibly utilized. Similarly, as compared to the whole-body utilization rate, there was a relatively high turnover rate of retinol in the kidneys, carcass, and liver (9.0, 8.2, and 5.8 micrograms retinol equivalents/day, respectively), coupled with a high degree of recycling of vitamin A through these tissues. Of the total vitamin A that entered the liver from all sources including the diet, approximately 86% was mobilized into the plasma. Similarly, of the vitamin A that entered the carcass, approximately 76% was returned to the plasma. All of the retinol that entered the kidneys was modeled as recycling to the plasma. The present studies provide quantitative and descriptive evidence of an efficient metabolism of vitamin A from absorption through turnover and utilization in rats with very low vitamin A status. Furthermore, although their body stores of vitamin A were extremely low, these rats maintained a high level of recycling of vitamin A throughout the body.

Levels of retinol and retinyl esters in plasma and urine of dogs with urolithiasis.

Vitamin A (VA) deficiency and Tamm-Horsfall glycoprotein (THP), a protein that binds retinol and retinyl esters in canine urine, might be involved in the pathogenesis of urolithiasis in dogs. In the present study, we assessed levels of retinol, retinyl esters, retinol-binding protein (RBP) and THP in plasma and urine of dogs with a history of urolithiasis (n = 25) compared with clinically healthy controls (n = 18). Plasma retinol concentrations were higher in dogs with uroliths of struvit (P < 0.01), calcium oxalate (P < 0.05), urate (P < 0.01) and cysteine, but there were no differences in the concentrations of plasma RBP and retinyl esters. Excretion of urinary retinol and retinyl esters were tentatively, but not significantly higher in the stone-forming groups, which was accompanied by increased levels of urinary RBP (P < 0.01) and lower excretions in THP (P < 0.01). The results show that VA deficiency may be excluded as a potential cause for canine urolithiasis. However, the occurrence of RBP and a concomitant reduction of THP in urine indicates a disturbed kidney function as cause or consequence of stone formation in dogs.