[show abstract][hide abstract] ABSTRACT: PURPOSE OF REVIEW: For a number of years, there has been increasing interest in the concept of directly targeting intestinal phosphate transport to control hyperphosphatemia in chronic kidney disease. However, progress has been slow due to the paucity of information on the mechanisms involved in intestinal phosphate absorption. This editorial highlights the most recent developments in our understanding of this process and the role of the intestine in the maintenance of phosphate balance. RECENT FINDINGS: Recent studies in NaPi-IIb knockout mice have confirmed that this transport protein plays a significant role in intestinal phosphate absorption and is critical in the proposed feed-forward mechanism between the small intestine and kidney, which helps to maintain normal phosphate balance and steady-state plasma phosphate concentrations. In addition, renal failure-induced hyperphosphatemia is attenuated in NaPi-IIb knockout mice, confirming that NaPi-IIb is a suitable target in the prevention and treatment of hyperphosphatemia. SUMMARY: Recent findings suggest that consumption of processed foods containing phosphate preservatives may lead to excessive phosphate exposure (if not overload), toxicity, and cardiovascular disease in the general population, as well as in patients with declining renal function. Therefore, establishing more effective ways of targeting the intestine to limit dietary phosphate absorption could have wide-reaching health benefits.
Current Opinion in Nephrology and Hypertension 05/2013; · 3.96 Impact Factor
[show abstract][hide abstract] ABSTRACT: The inhibitory effects of the angiotensin-converting enzyme (ACE)-ANG II-angiotensin type 1 (AT(1)) receptor axis on jejunal glucose uptake and the reduced expression of this system in type 1 diabetes mellitus (T1DM) have been documented previously. The ACE2-ANG-(1-7)-Mas receptor axis is thought to oppose the actions of the ACE-ANG II-AT(1) receptor axis in heart, liver, and kidney. However, the possible involvement of the ACE2-ANG-(1-7)-Mas receptor system on enhanced jejunal glucose transport in T1DM has yet to be determined. Rat everted jejunum and Caco-2 cells were used to determine the effects of ANG-(1-7) on glucose uptake and to study the ACE2-ANG-(1-7)-Mas receptor signaling pathway. Expression of target gene and protein in jejunal enterocytes and human Caco-2 cells were quantified using real-time PCR and Western blotting. T1DM increased jejunal protein and mRNA expression of ACE2 (by 59 and 173%, respectively) and Mas receptor (by 55 and 100%, respectively) in jejunum. One millimolar ANG-(1-7) reduced glucose uptake in jejunum and Caco-2 cells by 30.6 and 30.3%, respectively, effects that were abolished following addition of 1 μM A-779 (a Mas receptor blocker) or 1 μM GF-109203X (protein kinase C inhibitor) to incubation buffer for jejunum or Caco-2 cells, respectively. Finally, intravenous treatment of animals with ANG-(1-7) significantly improved oral glucose tolerance in T1DM but not control animals. In conclusion, enhanced activity of the ACE2-ANG-(1-7)-Mas receptor axis in jejunal enterocytes is likely to moderate the T1DM-induced increase in jejunal glucose uptake resulting from downregulation of the ACE-ANG II-AT(1) receptor axis. Therefore, altered activity of both ACE and ACE2 systems during diabetes will determine the overall rate of glucose transport across the jejunal epithelium.
AJP Endocrinology and Metabolism 07/2012; 303(5):E669-81. · 4.51 Impact Factor
[show abstract][hide abstract] ABSTRACT: The secoiridoids 3,4-dihydroxyphenylethanol-elenolic acid (3,4-DHPEA-EA) and 3,4-dihydroxyphenylethanol-elenolic acid dialdehyde (3,4-DHPEA-EDA) account for approximately 55 % of the phenolic content of olive oil and may be partly responsible for its reported human health benefits. We have investigated the absorption and metabolism of these secoiridoids in the upper gastrointestinal tract. Both 3,4-DHPEA-EDA and 3,4-DHPEA-EA were relatively stable under gastric conditions, only undergoing limited hydrolysis. Both secoiridoids were transferred across a human cellular model of the small intestine (Caco-2 cells). However, no glucuronide conjugation was observed for either secoiridoid during transfer, although some hydroxytyrosol and homovanillic alcohol were formed. As Caco-2 cells are known to express only limited metabolic activity, we also investigated the absorption and metabolism of secoiridoids in isolated, perfused segments of the jejunum and ileum. Here, both secoiridoids underwent extensive metabolism, most notably a two-electron reduction and glucuronidation during the transfer across both the ileum and jejunum. Unlike Caco-2 cells, the intact small-intestinal segments contain NADPH-dependent aldo-keto reductases, which reduce the aldehyde carbonyl group of 3,4-DHPEA-EA and one of the two aldeydic carbonyl groups present on 3,4-DHPEA-EDA. These reduced forms are then glucuronidated and represent the major in vivo small-intestinal metabolites of the secoiridoids. In agreement with the cell studies, perfusion of the jejunum and ileum also yielded hydroxytyrosol and homovanillic alcohol and their respective glucuronides. We suggest that the reduced and glucuronidated forms represent novel physiological metabolites of the secoiridoids that should be pursued in vivo and investigated for their biological activity.
The British journal of nutrition 03/2011; 105(11):1607-18. · 3.45 Impact Factor
[show abstract][hide abstract] ABSTRACT: Erythropoietin is produced by the kidney and stimulates erythropoiesis; however, in chronic renal disease its levels are reduced and patients develop anemia that is treatable with iron and recombinant hormone. The mechanism by which erythropoietin improves iron homeostasis is still unclear, but it may involve suppression of the iron regulatory peptide hepcidin and/or a direct effect on intestinal iron absorption. To investigate these possibilities, we used the well-established 5/6th nephrectomy rat model of chronic renal failure with or without human recombinant erythropoietin treatment. Monolayers of human intestinal Caco-2 cells were also treated with erythropoietin to measure any direct effects of this hormone on intestinal iron transport. Nephrectomy increased hepatic hepcidin expression and decreased intestinal iron absorption; these effects were restored to levels found in sham-operated rats on erythropoietin treatment of the rats with renal failure. In Caco-2 cells, the addition of erythropoietin significantly increased the expression of apical divalent metal transporter 1 (DMT1) and basolateral ferroportin and, consequently, iron transport across the monolayer. Taken together, our results show that erythropoietin not only exerts a powerful inhibitory action on the expression of hepcidin, thus permitting the release of iron from reticuloendothelial macrophages and intestinal enterocytes, but also acts directly on enterocytes to increase iron absorption.
Kidney International 10/2010; 78(7):660-7. · 7.92 Impact Factor
[show abstract][hide abstract] ABSTRACT: Transport of phosphate across intestinal and renal epithelia is essential for normal phosphate balance, yet we know less about the mechanisms and regulation of intestinal phosphate absorption than we do about phosphate handling by the kidney. Recent studies have provided strong evidence that the sodium-phosphate cotransporter NaPi-IIb is responsible for sodium-dependent phosphate absorption by the small intestine, and it might be that this protein can link changes in dietary phosphate to altered renal phosphate excretion to maintain phosphate balance. Evidence is also emerging that specific regions of the small intestine adapt differently to acute or chronic changes in dietary phosphate load and that phosphatonins inhibit both renal and intestinal phosphate transport. This review summarizes our current understanding of the mechanisms and control of intestinal phosphate absorption and how it may be related to renal phosphate reabsorption; it also considers the ways in which the gut could be targeted to prevent, or limit, hyperphosphatemia in chronic and end-stage renal failure.
[show abstract][hide abstract] ABSTRACT: Streptozotocin-induced (Type 1) diabetes mellitus (T1DM) in rats promotes jejunal glucose transport, but the trigger for this response remains unclear. Our recent work using euglycemic rats has implicated the enterocyte renin-angiotensin system (RAS) in control of sodium-dependent glucose transporter (SGLT1)-mediated glucose uptake across the jejunal brush border membrane (BBM). The aim of the present study was to examine whether expression of enterocyte RAS components is influenced by T1DM. The effects of mucosal addition of angiotensin II (AII) on [(14)C]-D-glucose uptake by everted diabetic jejunum was also determined. Two-week diabetes caused a fivefold increase in blood glucose level and reduced mRNA and protein expression of AII type 1 (AT(1)) and AT(2) receptors and angiotensin-converting enzyme in isolated jejunal enterocytes. Angiotensinogen expression was, however, stimulated by diabetes while renin was not detected in either control or diabetic enterocytes. Diabetes stimulated glucose uptake into everted jejunum by 58% and increased the BBM expression of SGLT1 and facilitated glucose transporter 2 (GLUT2) proteins, determined by Western blotting by 25% and 135%, respectively. Immunohistochemistry confirmed an enhanced BBM expression of GLUT2 in diabetes and also showed that this was due to translocation of the transporter from the basolateral membrane to BBM. AII (5 microM) or L-162313 (1 microM), a nonpeptide AII analog, decreased glucose uptake by 18% and 24%, respectively, in diabetic jejunum. This inhibitory action was fully accountable by an action on SGLT1-mediated transport and was abolished by the AT(1) receptor antagonist losartan (1 microM). The decreased inhibitory action of AII on in vitro jejunal glucose uptake in diabetes compared with that noted previously in jejunum from normal animals is likely to be due to reduced RAS expression in diabetic enterocytes, together with a disproportionate increase in GLUT2, compared with SGLT1 expression at the BBM.
[show abstract][hide abstract] ABSTRACT: The role of putative humoral factors, known as phosphatonins, in phosphate homeostasis and the relationship between phosphate handling by the kidney and gastrointestinal tract are incompletely understood. Matrix extracellular phosphoglycoprotein (MEPE), one of several candidate phosphatonins, promotes phosphaturia, but whether it also affects intestinal phosphate absorption is unknown. Here, using the in situ intestinal loop technique, we demonstrated that short-term infusion of MEPE inhibits phosphate absorption in the jejunum but not the duodenum. Simultaneous measurement of urinary phosphate excretion suggests that the phosphaturic action of MEPE correlates with a significant reduction in the protein levels of the renal sodium-phosphate co-transporter NaPi-IIa in the proximal convoluted tubules of the outer renal cortex, assessed by Western blotting and immunohistochemistry. This short-term inhibitory effect of MEPE on renal and intestinal phosphate handling occurred without any changes in circulating levels of parathyroid hormone, 1,25-dihydroxyvitamin D(3), or fibroblast growth factor 23. Taken together, these findings suggest that MEPE is a candidate phosphatonin involved in phosphate homeostasis, acting in both the kidney and the gastrointestinal tract.
Journal of the American Society of Nephrology 12/2008; 19(12):2313-20. · 8.99 Impact Factor
[show abstract][hide abstract] ABSTRACT: The concept of a regulatory link between the gastrointestinal tract and kidneys is not new. The idea that dietary intake and composition can affect renal function is perhaps self-evident, but defining this relationship, especially in terms of sensors and effectors, is proving more difficult. That the gastrointestinal tract can exert some control over renal function was strengthened by the early observation that oral ingestion of a sodium chloride load has a greater natriuretic effect than when the same amount is given intravenously. This effect was subsequently shown to be independent of changes in aldosterone and atrial natriuretic peptide, although not necessarily angiotensin-II. However, the nature of any intestinal natriuretic peptide remains uncertain, despite suggestions that various gut-derived hormones, including guanylin and uroguanylin, may be involved. There is also an emerging concept of gastrointestinal taste and taste-like receptor mechanisms present throughout the gastrointestinal tract, which may govern the excretion of other key electrolytes, including potassium and phosphate. The evidence for gut sensors of nutrients such as proteins, amino acids, glucose, and acid is now becoming more established. Thus, we can anticipate the existence and eventual characterization of several gut ion sensors.
Annual Review of Physiology 02/2008; 70:379-403. · 19.55 Impact Factor
[show abstract][hide abstract] ABSTRACT: There is increasing evidence that locally produced angiotensin AII (AII) regulates the function of many tissues, but the involvement of enterocyte-derived AII in the control of intestinal transport is unknown. This study examined whether there is a local renin-angiotensin system (RAS) in rat villus enterocytes and assessed the effects of AII on SGLT1-dependent glucose transport across the brush border membrane (BBM). Gene and protein expression of angiotensinogen, ACE, and AT(1) and AT(2) receptors were studied in jejunal and ileal enterocytes using immunocytochemistry, Western blotting and RT-PCR. Mucosal uptake of d-[(14)C]glucose by everted intestinal sleeves before and after addition of AII (0-100 nm) to the mucosal buffer was measured in the presence or absence of the AT(1) receptor antagonist losartan (1 microm). Immunocytochemistry revealed the expression of angiotensinogen, ACE, and AT(1) and AT(2) receptors in enterocytes; immunoreactivity of AT(1) receptor and angiotensinogen proteins was especially pronounced at the BBM. Expression of angiotensinogen and AT(1) and AT(2) receptors, but not ACE, was greater in the ileum than the jejunum. Addition of AII to mucosal buffer inhibited phlorizin-sensitive (SGLT1-dependent) jejunal glucose uptake in a rapid and dose-dependent manner and reduced the expression of SGLT1 at the BBM. Losartan attenuated the inhibitory action of AII on glucose uptake. AII did not affect jejunal uptake of l-leucine. The detection of RAS components at the enterocyte BBM, and the rapid inhibition of SGLT1-dependent glucose uptake by luminal AII suggest that AII secretion exerts autocrine control of intestinal glucose transport.
The Journal of Physiology 11/2007; 584(Pt 2):613-23. · 4.38 Impact Factor
[show abstract][hide abstract] ABSTRACT: GLUT2 is the main renal glucose transporter upregulated by hyperglycaemia, when it becomes detectable at the brush border membrane (BBM). Since glucose-induced protein kinase C (PKC) activation in the kidney is linked to diabetic nephropathy, we investigated the effect of glycaemic status on the protein levels of PKC isoforms alpha, betaI, betaII, delta and epsilon in the proximal tubule, as well as the relationship between them and changes in GLUT2 production at the BBM.
Plasma glucose concentrations were modulated in rats by treatment with nicotinamide 15 min prior to induction of diabetes with streptozotocin. Levels of GLUT2 protein and PKC isoforms in BBM were measured by western blotting. Additionally, the role of calcium signalling and PKC activation on facilitative glucose transport was examined by measuring glucose uptake in BBM vesicles prepared from proximal tubules that had been incubated either with thapsigargin, which increases cytosolic calcium, or with the PKC activator phorbol 12-myristate,13-acetate (PMA).
Thapsigargin and PMA enhanced GLUT-mediated glucose uptake, but had no effect on sodium-dependent glucose transport. Diabetes significantly increased the protein levels of GLUT2 and PKC-betaI at the BBM. Levels of GLUT2 and PKC-betaI correlated positively with plasma glucose concentration. Diabetes had no effect on BBM levels of alpha, betaII, delta or epsilon isoforms of PKC.
Enhanced GLUT2-mediated glucose transport across the proximal tubule BBM during diabetic hyperglycaemia is closely associated with increased PKC-betaI. Thus, altered levels of GLUT2 and PKC-betaI proteins in the BBM may be important factors in the pathogenic processes underlying diabetic renal injury.
[show abstract][hide abstract] ABSTRACT: Hyperphosphatemia is an important consequence of chronic renal failure (CRF). Lowering of the plasma phosphate concentration is believed to be critical in the management of patients with CRF, especially those on dialysis. Reports of the effect of CRF on the intestinal handling of phosphate in vitro have been conflicting; but what happens in vivo has not been studied. What effect a reduction in the dietary phosphate intake has on intestinal phosphate absorption in CRF in vivo is unclear. In this study, we have used the in situ intestine loop technique to determine intestinal phosphate absorption in the 5/6-nephrectomy rat model of CRF under conditions of normal and restricted dietary phosphate intake. In this model of renal disease, we found that there is no significant change in the phosphate absorption in either the duodenum or jejunum regardless of the dietary phosphate intake. There was also no change in the expression of the messenger RNA of the major intestinal phosphate carrier the sodium-dependent-IIb transporter. Furthermore, we found no change in the intestinal villus length or in the location of phosphate uptake along the villus. Our results indicate that in CRF, unlike the kidney, there is no reduction in phosphate transport across the small intestine. This makes intestinal phosphate absorption a potential target in the prevention and treatment of hyperphosphatemia.
Kidney International 08/2007; 72(2):166-73. · 7.92 Impact Factor
[show abstract][hide abstract] ABSTRACT: Resveratrol has been widely investigated for its potential health properties, although little is known about its metabolism in vivo. Here we investigated the distribution of metabolic products of [3H]trans-resveratrol, following gastric administration. At 2 h, plasma concentrations reached 1.7 % of the administered dose, whilst liver and kidney concentrations achieved 1.0 and 0.6 %, respectively. Concentrations detected at 18 h were lower, being only 0.5 % in plasma and a total of 0.35 % in tissues. Furthermore, whilst kidney and liver concentrations fell to 10 and 25 %, respectively, of concentrations at 2 h, the brain retained 43 % of that measured at 2 h. Resveratrol-glucuronide was identified as the major metabolite, reaching 7 microm in plasma at 2 h. However, at 18 h the main form identified in liver, heart, lung and brain was native resveratrol aglycone, indicating that it is the main form retained in the tissues. No phenolic degradation products were detected in urine or tissues, indicating that, unlike flavonoids, resveratrol does not appear to serve as a substrate for colonic microflora. The present study provides additional information about the nature of resveratrol metabolites and which forms might be responsible for its in vivo biological effects.
British Journal Of Nutrition 08/2006; 96(1):62-70. · 3.30 Impact Factor
[show abstract][hide abstract] ABSTRACT: We have conducted a detailed investigation into the absorption, metabolism and microflora-dependent transformation of hydroxytyrosol (HT), tyrosol (TYR) and their conjugated forms, such as oleuropein (OL). Conjugated forms underwent rapid hydrolysis under gastric conditions, resulting in significant increases in the amount of free HT and TYR entering the small intestine. Both HT and TYR transferred across human Caco-2 cell monolayers and rat segments of jejunum and ileum and were subject to classic phase I/II biotransformation. The major metabolites identified were an O-methylated derivative of HT, glucuronides of HT and TYR and a novel glutathionylated conjugate of HT. In contrast, there was no absorption of OL in either model. However, OL was rapidly degraded by the colonic microflora resulting in the formation of HT. Our study provides additional information regarding the breakdown of complex olive oil polyphenols in the GI tract, in particular the stomach and the large intestine.
Free Radical Research 07/2006; 40(6):647-58. · 3.28 Impact Factor
[show abstract][hide abstract] ABSTRACT: Previously, it was thought that intestinal phosphate transport occurred exclusively in the proximal small intestine of rodents and humans. However, a recent study has demonstrated that the ileum of mice contributes significantly to the absorption of dietary phosphate, but it is not known whether this region is also an important site of phosphate absorption in the rat. In the present study, we have investigated the mRNA and protein levels of the sodium-phosphate cotransporter, NaPi-IIb, in three regions of rat and mouse small intestine, and related its expression levels to the rate of net phosphate absorption, as measured using the in situ intestinal loop technique. 1,25-Dihydroxyvitamin D3 is an important physiological regulator of intestinal phosphate absorption that increases phosphate transport in both the duodenum and jejunum of the rat. Based on the recently proposed regional profile of phosphate absorption along the mouse small intestine, we have re-evaluated the effects of 1,25-dihydroxyvitamin D3 using three distinct regions of the mouse and rat small intestine. Our studies have revealed important differences in the intestinal handling of phosphate between mice and rats. In mice, maximal phosphate absorption occurs in the ileum, which is paralleled by the highest expression levels of NaPi-IIb mRNA and protein. In contrast, in rats maximal absorption occurs in the duodenum with very little absorption occurring in the ileum, which is similar to the pattern reported in humans. However, in both rodent species only the jejunum shows an increase in phosphate absorption in response to treatment with 1,25-dihydroxyvitamin D3.
[show abstract][hide abstract] ABSTRACT: Studies have suggested that diets rich in polyphenols such as flavonoids may lead to a reduced risk of gastrointestinal cancers. We demonstrate the ability of monomeric and dimeric flavanols to scavenge reactive nitrogen species derived from nitrous acid. Both epicatechin and dimer B2 (epicatechin dimer) inhibited nitrous acid-induced formation of 3-nitrotyrosine and the formation of the carcinogenic N-nitrosamine, N-nitrosodimethylamine. The reaction of monomeric and dimeric epicatechin with nitrous acid led to the formation of mono- and di-nitroso flavanols, whereas the reaction with hesperetin resulted primarily in the formation of nitrated products. Although, epicatechin was transferred across the jejunum of the small intestine yielding metabolites, its nitroso form was not absorbed. Dimer B2 but not epicatechin monomer inhibited the proliferation of, and triggered apoptosis in, Caco-2 cells. The latter was accompanied by caspase-3 activation and reductions in Akt phosphorylation, suggesting activation of apoptosis via inhibition of prosurvival signaling. Furthermore, the dinitroso derivative of dimer B2, and to a lesser extent the dinitroso-epicatechin, also induced significant toxic effects in Caco-2 cells. The inhibitory effects on cellular proliferation were paralleled by early inhibition of ERK 1/2 phosphorylation and later reductions in cyclin D1 levels, indicating modulation of cell cycle regulation in Caco-2 cells. These effects highlight multiple routes in which dietary derived flavanols may exert beneficial effects in the gastrointestinal tract.
Free Radical Biology and Medicine 02/2006; 40(2):323-34. · 5.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: Recent reports have demonstrated various cardiovascular and neurological benefits associated with the consumption of foods rich in anthocyanidins. However, information regarding absorption, metabolism, and especially, tissue distribution are only beginning to accumulate. In the present study, we investigated the occurrence and the kinetics of various circulating pelargonidin metabolites, and we aimed at providing initial information with regard to tissue distribution. Based on HPLC and LC-MS analyses we demonstrate that pelargonidin is absorbed and present in plasma following oral gavage to rats. In addition, the main structurally related pelargonidin metabolite identified in plasma and urine was pelargonidin glucuronide. Furthermore, p-hydroxybenzoic acid, a ring fission product of pelargonidin, was detected in plasma and urine samples obtained at 2 and 18 h after ingestion. At 2 h post-gavage, pelargonidin glucuronide was the major metabolite detected in kidney and liver, with levels reaching 0.5 and 0.15 nmol pelargonidin equivalents/g tissue, respectively. Brain and lung tissues contained detectable levels of the aglycone, with the glucuronide also present in the lungs. Other tissues, including spleen and heart, did not contain detectable levels of pelargonidin or ensuing metabolites. At 18 h post-gavage, tissue analyses did not reveal detectable levels of the aglycone nor of pelargonidin glucuronides. Taken together, our results demonstrate that the overall uptake of the administered pelargonidin was 18 % after 2 h, with the majority of the detected levels located in the stomach. However, the amounts recovered dropped to 1.2 % only 18 h post-gavage, with the urine and faecal content constituting almost 90 % of the total recovered pelargonidin.
British Journal Of Nutrition 02/2006; 95(1):51-8. · 3.30 Impact Factor
[show abstract][hide abstract] ABSTRACT: Only 10% of dietary iron is absorbed in the duodenum which implies that 90% (approximately 9 mg day(-1)) reaches the lower small intestine and colon. Therefore the purpose of this study was to assess the iron transport capacity of the rat proximal colon and to determine whether iron absorption is regulated by changes in dietary iron content.
Rats were fed for 14 days on either iron adequate (44 mg Fe kg(-1) diet) or iron-deficient (< 0.5 mg Fe kg(-1) diet) diets. The 59Fe transport across the colonic epithelium and its subsequent appearance in the blood were measured in vivo. In separate studies the colon was excised and used to measure divalent metal transporter expression.
Divalent metal transporter (DMT1) was expressed at the apical membrane of the surface epithelium in rat proximal colon. In animals fed an iron-deficient diet, DMT1 mRNA and protein expression were increased. This was accompanied by a significant increase in tissue 59Fe uptake.
The proximal colon can absorb non-haem iron from the intestinal lumen. The purpose of this mechanism remains to be elucidated.
European Journal of Clinical Investigation 01/2006; 36(1):35-40. · 3.37 Impact Factor
[show abstract][hide abstract] ABSTRACT: Recent reports have demonstrated various cardiovascular and neurological benefits associated with the consumption of foods rich in anthocyanidins. However, information regarding absorption, metabolism, and especially, tissue distribution are only beginning to accumulate. In the present study, we investigated the occurrence and the kinetics of various circulating pelargonidin metabolites, and we aimed at providing initial information with regard to tissue distribution. Based on HPLC and LC-MS analyses we demonstrate that pelargonidin is absorbed and present in plasma following oral gavage to rats. In addition, the main structurally related pelargonidin metabolite identified in plasma and urine was pelargonidin glucuronide. Furthermore, p-hydroxybenzoic acid, a ring fission product of pelargonidin, was detected in plasma and urine samples obtained at 2 and 18h after ingestion. At 2h post-gavage, pelargonidin glucuronide was the major metabolite detected in kidney and liver, with levels reaching 0·5 and 0·15nmol pelargonidin equivalents/g tissue, respectively. Brain and lung tissues contained detectable levels of the aglycone, with the glucuronide also present in the lungs. Other tissues, including spleen and heart, did not contain detectable levels of pelargonidin or ensuing metabolites. At 18h post-gavage, tissue analyses did not reveal detectable levels of the aglycone nor of pelargonidin glucuronides. Taken together, our results demonstrate that the overall uptake of the administered pelargonidin was 18% after 2h, with the majority of the detected levels located in the stomach. However, the amounts recovered dropped to 1·2% only 18h post-gavage, with the urine and faecal content constituting almost 90% of the total recovered pelargonidin.
The British journal of nutrition 12/2005; 95(01):51 - 58. · 3.45 Impact Factor