The flavonol quercetin activates basolateral K(+) channels in rat distal colon epithelium

1. The flavonol quercetin has been shown to activate a Cl(-) secretion in rat colon. Unlike the secretory activity of the related isoflavone genistein, quercetin's secretory activity does not depend on cyclic AMP; instead, it depends on Ca(2+). We investigated the possible involvement of Ca(2+) dependent basolateral K(+) channels using apically permeabilized rat distal colon epithelium mounted in Ussing chambers. 2. In intact epithelium, quercetin induced an increase in short-circuit current (I(sc)), which was diminished by the Cl(-) channel blockers NPPB and DPC, but not by glibenclamide, DIDS or anthracene-9-carboxylic acid. The effect of the flavonol was also inhibited by several serosally applied K(+) channel blockers (Ba(2+), quinine, clotrimazole, tetrapentylammonium, 293B), whereas other K(+) channel blockers failed to influence the quercetin-induced increase in I(sc) (tetraethylammonium, charybdotoxin). 3. The apical membrane was permeabilized by mucosal addition of nystatin and a serosally directed K(+) gradient was applied. The successful permeabilization was confirmed by experiments demonstrating the failure of bumetanide to inhibit the carbachol-induced current. 4. In apically permeabilized epithelium, quercetin induced a K(+) current (I(K)), which was neither influenced by ouabain nor by bumetanide. Whereas DPC, NPPB, charybdotoxin and 293B failed to inhibit this I(K), quinine, Ba(2+), clotrimazole and tetrapentylammonium were effective blockers of this current. 5. We conclude from these results that at least part of the quercetin-induced Cl(-) secretion can be explained by an activation of basolateral K(+) channels.     

Enriched cereal bars are more effective in increasing plasma quercetin compared with quercetin from powder-filled hard capsules

The flavonol quercetin, is one of the major flavonoids found in edible plants. The bioavailability of quercetin in humans may be influenced by the food matrix in which it is consumed as well as by its chemical and physical form. The objective of the present study was to investigate the biokinetics of quercetin from quercetin-enriched cereal bars and quercetin powder-filled hard capsules. In a randomised, single-blinded, diet-controlled cross-over study, six healthy women aged 22-28 years took a single oral dose of approximately 130?mg quercetin equivalents from either quercetin-enriched cereal bars (containing 93·3?% quercetin aglycone plus 6·7?% quercetin-4'-glucoside) or quercetin powder-filled hard capsules (100?% quercetin aglycone). Blood samples were drawn before and after quercetin administration over a 24?h period. The concentrations of quercetin and its monomethylated derivatives, isorhamnetin (3'-O-methyl quercetin) and tamarixetin (4'-O-methyl quercetin), were measured by HPLC with fluorescence detection after plasma enzymatic treatment. The systemic availability as determined by comparing the plasma concentration-time curves of quercetin was found to be five times and the cmax values six times higher after ingestion of 130?mg quercetin by quercetin-enriched cereal bars than after ingestion by quercetin capsules. In contrast, tmax did not differ significantly between the two treatments. The cmax values for isorhamnetin and tamarixetin were four and nine times higher after ingestion of quercetin by quercetin-enriched cereal bars than after ingestion by quercetin capsules. In conclusion, quercetin from quercetin-enriched cereal bars is significantly more bioavailable than from quercetin powder-filled hard capsules.     

Active absorption of selenate by rat ileum

Intestinal absorption of selenate and selenite in rats was investigated in vitro by using everted sacs of the duodenum, jejunum and ileum. Only the ileal sacs incubated with selenate accumulated selenium in the serosal fluid during the incubation. Selenium transport across the ileum did not occur against a concentration gradient when selenite instead of selenate was present in the incubation medium. Sulfate and thiosulfate significantly inhibited ileal selenate transport. Decreasing the activity of the Na+,K+-ATPase, by the addition of ouabain, resulted in a significant reduction of concentrative selenate transport by the ileum. Furthermore L-leucine, but not D-glucose and D-galactose, significantly reduced selenium absorption by ileal sacs incubated with selenate. It is concluded from these results that selenate is transported actively by the ileal mucosa and that a common transport mechanism for selenate and sulfate exists. The Na+-gradient across the intestinal brush border membrane seems to be capable of energizing active ileal selenate transport.     

Dermatoglyphische Untersuchungen bei Kindern mit embryonalen Tumoren

Dermatoglyphics were analyzed in 60 children with embryonic tumors. In comparison with normal children, several differences were found. Thus, the embryonal origin of the different tumors is underlined and the hypothesis of embryonic tumors as malformations is sustained. These tumors seem to be the clinically most important manifestation of a much more comprehensive malformation syndrome, which is not yet known in all its details.     

The secretory response of the rat colon to the flavonol quercetin is dependent on Ca2+-calmodulin

The dietary flavonol quercetin induces chloride secretion in rat intestine. To clarify the underlying mechanisms, experiments were performed in Ussing chambers with tissue from rat proximal and distal colon. Quercetin induced an increase in short-circuit current (Isc), which was largely independent of submucosal neurons, as it was not affected by the neurotoxin tetrodotoxin. The effect of quercetin was blocked by the calmodulin antagonists trifluoperazine and ophiobolin A and was diminished by a blocker of Ca2+ release from intracellular stores (TMB-8), whereas the muscarinic receptor antagonist atropine was ineffective. The quercetin-induced Isc was abolished in Ca2+-free solution. The flavonol was able to further increase Isc after maximal stimulation of the cAMP pathway by forskolin. The Isc increase by the flavonol was differently affected by two analogous phosphodiesterase inhibitors. Whereas 3-isobutyl-1-methylxanthine (IBMX) antagonized the effect of quercetin, 8-methoxymethyl-IBMX had no effect. Both phosphodiesterase inhibitors similarly influenced the Isc increase induced by forskolin. These results indicate that the chloride secretion induced by quercetin in rat colon depends on Ca2+ and calmodulin. The cAMP pathway and inhibition of phosphodiesterase appear not to be responsible for the secretory activity of the flavonol.     

Effects of Quercetin and Catechin on Hepatic Glutathione-S Transferase (GST), NAD(P)H Quinone Oxidoreductase 1 (NQO1), and Antioxidant Enzyme Activity Levels in Rats

Cell culture data indicate that quercetin and catechin may affect the activity of phase II and antioxidant enzymes. However, little is known about the impact of dietary flavonoids in vivo. Therefore, the present study aimed to investigate the in vivo effects of the flavonoids quercetin and catechin on mRNA and activity levels of phase II enzymes glutathione-S transferase (GST) and NAD(P)H quinone oxidoreductase-1 (NQO1) in rat liver. Furthermore, the activity of the hepatic antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) was determined. Feeding male Wistar rats (3 × 6 animals) over 3 wk with semisynthetic diets enriched with quercetin and catechin (2 g/kg diet) did not affect liver enzyme activity of CAT, GPx, and SOD as well lipid peroxidation and glutathione levels. Dietary quercetin significantly decreased activity of hepatic GST (24%), whereas dietary catechin significantly decreased NQO1 activity (26%) compared to controls. Changes in GST and NQO1 activity were partly reflected on mRNA levels. Current data indicate that dietary flavonoids have little effects on liver oxidant/antioxidant status but do significantly affect the phase II enzymes GST and NQO1 in rat liver. This in turn may affect the ability of the organism to detoxify endogenous and exogenous xenobiotics.     

Transport of selenoamino acids and their sulfur analogues across the intestinal brush border membrane of pigs

Transport of selenomethionine (Se-Met) and its sulfur analogue, methionine (Met), across the pig jejunal brush border membrane (BBM) was investigated using isolated BBM vesicles. Experiments were also performed to gain insight into the transport mechanism(s) for selenocystine. Se-Met as well as Met were transported by a single, Na+-dependent, carrier-mediated process common for both amino acids. Evaluation of the kinetic parameters revealed no differences between Se-Met and Met in the maximal transport velocity (Vmax) or in the Michaelis constant (Km). Furthermore, transport of Se-Met and Met showed similar characteristics with respect to electrogenicity and substrate specificity. In addition, evidence was obtained for a competitive inhibition of cystine transport across the BBM by selenocystine and basic amino acids.     

Effect of apoE genotype and dietary quercetin on blood lipids and TNF-alpha levels in apoE3 and apoE4 targeted gene replacement mice

The aim of this study was to determine the effect of dietary quercetin supplementation on blood lipids and TNF-alpha levels according to the apoE genotype in apoE3 and apoE4 targeted gene replacement mice. In a two-factorial design female apoE3 and apoE4 mice were fed semi-synthetic diets without (controls) and with quercetin (2 mg/g diet) for 6 weeks. Feeding the quercetin-supplemented diets significantly increased plasma levels of quercetin and isorhamnetin both in apoE3 and apoE4 mice. There was no significant effect of apoE genotype on plasma quercetin levels. ApoE3 and apoE4 transgenic mice exhibited similar plasma levels of apoE and cholesterol which were not significantly affected by dietary quercetin supplementation. In mice receiving the basal diet without quercetin supplementation, levels of TNF-alpha in whole blood stimulated ex vivo with lipopolysaccharide were higher in apoE3 as compared to apoE4 transgenic mice. Dietary quercetin significantly lowered levels of TNF-alpha by 44 % in apoE3 mice relative to apoE3 mice receiving the unsupplemented diets. In apoE4 mice a moderate (20 %) but not significant decrease in TNF-alpha levels in response to the quercetin supplementation was evident. Following quercetin supplementation TNF-alpha levels were similar between apoE3 and apoE4 transgenic mice. Current findings indicate that apoE3 mice are more responsive to the TNF-alpha lowering properties of dietary quercetin supplementation as compared to apoE4 animals.     

Medium‐chain fatty acids ameliorate insulin resistance caused by high‐fat diets in rats

Background High dietary intake of saturated fat impairs insulin sensitivity and lipid metabolism. The influence of fatty acid chain length, however, is not yet fully understood, but evidence exists for different effects of saturated long‐chain (LC) versus saturated medium‐chain (MC) fatty acids (FA). Methods To investigate the effects of the FA chain length, male Wistar rats were fed high‐fat diets containing triacylglycerols composed of either MC‐ or LCFA for 4 weeks; rats fed maintenance diet served as a control. The animals underwent euglycemic hyperinsulinemic clamping or oral metabolic tolerance testing respectively; enzyme activities of mitochondrial (EC2.3.1.21 carnitine palmitoyl transferase) and peroxisomal (EC1.3.3.6 acyl‐CoA oxidase) FA oxidation were measured in liver and muscle. Results LCFA consumption resulted in higher fasted serum insulin and glucose concentrations compared to controls, while MCFA‐fed animals did not differ from controls. Insulin sensitivity was reduced by 30% in the LCFA group while the MCFA group did not differ from controls. Feeding MCFA resulted in the controls' lowered fasted and post‐prandial triacylglycerol concentration compared to LCFA, while triacylglycerol concentrations in muscle were higher in both high‐fat groups compared to controls. No diet‐induced changes were found in acyl‐CoA oxidase (ACO) activity (liver and muscle), while LCFA feeding significantly raised carnitine palmitoyltransferase activity. Conclusions The chain length of saturated fatty acids in isocaloric diets affects insulin sensitivity, lipid metabolism and mitochondrial fatty acid oxidation without influencing body weight. While dietary LCFA clearly impair insulin sensitivity and lipid metabolism, MCFA seem to protect from lipotoxicity and subsequent insulin resistance without caloric restriction. Copyright © 2009 John Wiley & Sons, Ltd.