Active components of Bupleurum chinense and Angelica biserrata showed analgesic effects in formalin induced pain by acting on Nav1.7.

ETHNOPHARMACOLOGY RELEVANCE: Pain is an unpleasant sensory and emotional experience, often accompanied by the occurrence of a variety of diseases. More than 800 kinds of traditional Chinese medicines (TCM) has now been reported for pain relief and several monomers have been developed into novel analgesic drugs. Bupleurum chinense and Angelica biserrata were representatives of the TCM that are currently available for the treatment of pain. AIM OF THE STUDY: The study aims to detect the potential analgesic activity of each monomer of Bupleurum chinense and Angelica biserrata and to explore whether Nav1.7 is one of the targets for its analgesic activity. MATERIALS AND METHODS: In this study, five monomers from Bupleurum chinense (Saikosaponin A, Saikosaponin B1, Saikosaponin B2, Saikosaponin C, Saikosaponin D) and five monomers from the Angelica biserrata (Osthole, Xanthotoxin, Imperatorin, Isoimperatorin, Psoralen) were examined by whole-cell patch-clamp on Nav1.7, which was closely associated with pain. Classical mouse pain models were also used to further verify the analgesic activity in vivo. RESULTS: The results showed that monomers of Saikosaponins and Angelica biserrata all inhibited the peak currents of Nav1.7, indicating that Nav1.7 might be involved in the analgesic mechanism of Saikosaponins and Angelica biserrata. Among them, Saikosaponin A and Imperatorin showed the strongest inhibitory effect on Nav1.7. Furthermore, both Saikosaponin A and Imperatorin showed inhibitory effects on thermal pain and formalin-induced pain in phase II in vivo. CONCLUSION: The results provide valuable information for future studies on the potential of TCM in alleviating pain.

Antiarrhythmic effects of dehydroevodiamine in isolated human myocardium and cardiomyocytes.

ETHNOPHARMACOLOGICAL RELEVANCE: Dehydroevodiamine alkaloid (DeHE), a bioactive component of the Chinese herbal medicine Wu-Chu-Yu (Evodiae frutus), exerted antiarrhythmic effect in guinea-pig ventricular myocytes. We further characterize the electromechanical effects of DeHE in the human atrial and ventricular tissues obtained from hearts of patients undergoing corrective cardiac surgery or heart transplantation. MATERIALS AND METHODS: The transmembrane potentials of human myocardia were recorded with a traditional microelectrode technique while sarcolemmal Na(+) and Ca(2+) currents in single human cardiomyocytes were measured by a whole-cell patch-clamp technique. The intracellular pH (pHi) and Na(+)-H(+) exchanger (NHE) activity were determined using BCECF-fluorescence in human atria. RESULTS: In human atria, DeHE (0.1-0.3 µM) depressed upstroke velocity, amplitude of action potential, and contractile force, both in slow and fast response action potential. Moreover, the similar depressant effects of DeHE were found in human ventricular myocardium. Both in isolated human atrial and ventricular myocytes, DeHE (0.1-1 µM) reversibly, concentration-dependently decreased the Na(+) and Ca(2+)currents. Moreover, DeHE (0.1 and 0.3 µM) suppressed delayed afterdepolarizations and aftercontractions, induced by epinephrine and high [Ca(2+)]o in atria. In human ventricular myocardium, the strophanthidin-induced triggered activities were attenuated by pretreating DeHE (0.3 µM). The resting pHi and NHE activity were also significantly increased by DeHE (0.1-0.3 µM). CONCLUSIONS: We concluded for the first time that, in the human hearts, DeHE could antagonize triggered arrhythmias induced by cardiotonic agents through a general reduction of the Na(+) and Ca(2+) inward currents, while increase of resting pHi and NHE activity.

New diterpenoid alkaloids from Aconitum coreanum and their anti-arrhythmic effects on cardiac sodium current.

Two new diterpenoid alkaloids, Guan-Fu base J (GFJ, 1) and Guan-Fu base N (GFN, 2) along with nineteen known alkaloids (3-21) were isolated from the roots of Aconitum coreanum (Lèvl.) Rapaics, which is the raw material of a new approval anti-arrhythmia drug "Acehytisine Hydrochloride". The structures of isolated compounds were established by means of 1D, 2D NMR spectroscopic and chemical methods. All isolates obtained in the present study were evaluated for their inhibitory effects on blocking the ventricular specific sodium current using a whole-cell patch voltage-clamp technique. Among these 21 compounds, Guan-Fu base S (GFS, 3) showed the strongest inhibitory effect with an IC50 value of 3.48 µM, and only hetisine-type C20 diterpenoid alkaloids showed promising IC50 values for further development.

Physiological functions of beneficial elements.

Aluminum (Al), cobalt (Co), sodium (Na), selenium (Se), and silicon (Si) are considered beneficial elements for plants: they are not required by all plants but can promote plant growth and may be essential for particular taxa. These beneficial elements have been reported to enhance resistance to biotic stresses such as pathogens and herbivory, and to abiotic stresses such as drought, salinity, and nutrient toxicity or deficiency. The beneficial effects of low doses of Al, Co, Na and Se have received little attention compared to toxic effects that typically occur at higher concentrations. Better understanding of the effects of beneficial elements is important to improve crop productivity and enhance plant nutritional value for a growing world population.

The Na+-dependent L-ascorbic acid transporter SVCT2 expressed in brainstem cells, neurons, and neuroblastoma cells is inhibited by flavonoids.

Ascorbic acid (AA) is best known for its role as an essential nutrient in humans and other species. As the brain does not synthesize AA, high levels are achieved in this organ by specific uptake mechanisms, which concentrate AA from the bloodstream to the CSF and from the CSF to the intracellular compartment. Two different isoforms of sodium-vitamin C co-transporters (SVCT1 and SVCT2) have been cloned. Both SVCT proteins mediate high affinity Na(+)-dependent L-AA transport and are necessary for the uptake of vitamin C in many tissues. In the adult brain the expression of SVCT2 was observed in the hippocampus and cortical neurons by in situ hybridization; however, there is no data regarding the expression and distribution of this transporter in the fetal brain. The expression of SVCT2 in embryonal mesencephalic neurons has been shown by RT-PCR suggesting an important role for vitamin C in dopaminergic neuronal differentiation. We analyze SVCT2 expression in human and rat developing brain by RT-PCR. Additionally, we study the normal localization of SVCT2 in rat fetal brain by immunohistochemistry and in situ hybridization demonstrating that SVCT2 is highly expressed in the ventricular and subventricular area of the rat brain. SVCT2 expression and function was also confirmed in neurons isolated from brain cortex and cerebellum. The kinetic parameters associated with the transport of AA in cultured neurons and neuroblastoma cell lines were also studied. We demonstrate two different affinity transport components for AA in these cells. Finally, we show the ability of different flavonoids to inhibit AA uptake in normal or immortalized neurons. Our data demonstrates that brain cortex and cerebellar stem cells, neurons and neuroblastoma cells express SVCT2. Dose-dependent inhibition analysis showed that quercetin inhibited AA transport in cortical neurons and Neuro2a cells.

Fluid and electrolyte management in the premature infant.

Caring for the premature infant in the NICU requires knowledge and understanding of the physiologic adaptation to extrauterine life and how prematurity affects that transition. Nurses play an integral role in managing fluid and electrolyte balance in these infants. This article addresses postnatal adaptation and all aspects of fluid and electrolyte management of the preterm infant.

Valproate-dependent transcriptional regulation of GLAST/EAAT1 expression: involvement of Ying-Yang 1.

Valproate, a widely used anti-epileptic drug also employed in the treatment of neurological diseases such as bipolar disorder and migraine, regulates the glutamatergic and GABAergic systems, although its effects in cell physiology have not been thoroughly characterized. High concentrations of glutamate reached during abnormal neurotransmission if not removed properly, become neurotoxic. Glutamate clearance is carried out by high affinity Na(+)-dependent glutamate transporter systems. The glutamate/aspartate transporter GLAST/EAAT1 plays the major role in glutamate removal and is regulated at different levels: transcription, post-translational modifications and cytoplasmic trafficking. The aim of this work was to gain insight into a plausible effect of valproate in GLAST function. Using cultured Bergmann glia cells from chick cerebellum we demonstrate here that valproate exposure elicits a dual regulatory effect on GLAST. In the short-term, valproate increases its Na(+)-dependent [(3)H]-d-aspartate uptake activity in a cytochalasin B-sensitive manner. Interestingly, a synergism between valproate and a histone deacetylase inhibitor was observed. Long-term valproate treatment up-regulates chglast promoter activity, GLAST mRNA levels, GLAST molecules at the plasma membrane and its uptake activity. Furthermore, valproate induces histone 3 lysine 14 acetylation and regulates Ying-Yang 1 (YY1) transcriptional repression on the chglast promoter. These results suggest that valproate elicits its effect through its histone deacetylase inhibitor properties.

Knowledge of phosphorus compared with other nutrients in maintenance dialysis patients.

OBJECTIVE: This study's objective was to assess knowledge of phosphorus compared with other nutrients in patients undergoing maintenance dialysis (MD). DESIGN: We compared knowledge of phosphorus vs. other nutrients important to the MD diet (potassium, sodium, and protein) in patients undergoing hemodialysis (HD) and peritoneal dialysis (PD). We further measured gender, age, education level, and functional health literacy to assess correlations in patient nutrient knowledge. Nutrient knowledge was measured using a 25-item Chronic Kidney Disease Knowledge Assessment Tool for Nutrition (CKDKAT-N), and functional health literacy was measured using the short form of the Test of Functional Health Literacy in Adults (S-TOFHLA). SETTING AND PATIENTS: Patients received maintenance outpatient PD or HD at Wisconsin Dialysis, Inc. (Madison, WI). MAIN OUTCOME MEASURE: The main outcome measure was knowledge of phosphorus vs. knowledge of potassium, sodium, and protein. RESULTS: Forty-seven MD patients participated in the study (29 undergoing HD, 18 undergoing PD, 30 males, 17 females, average age of 58.6 (SD, 13.8) years, and average grade level of 1.4 (SD, 2.6) years of post-secondary education). Thirty-five participants had adequate health literacy, 4 had marginal health literacy, and 8 had inadequate health literacy. The CKDKAT-N scores ranged from 6-21 for 25 items, with a mean score of 13 (SD, 2.91). Knowledge of phosphorus compared with knowledge of other nutrients was poor (0.38 vs. 0.72, P = .003). In a comparison of HD vs. PD patient knowledge, both phosphorus (0.37 vs. 0.42, P = .231) and other nutrients (0.69 vs. 0.80, P = .115) were the same. CONCLUSION: Despite regular dietary instruction, patients undergoing MD have a poor knowledge of dietary phosphorus content, compared with knowledge of other nutrients important in chronic kidney disease. Interestingly, there was no difference in nutrition knowledge when comparing PD and HD patients, despite differences in education level and health literacy between groups.

The life-extending gene Indy encodes an exchanger for Krebs-cycle intermediates.

A longevity gene called Indy (for 'I'm not dead yet'), with similarity to mammalian genes encoding sodium-dicarboxylate cotransporters, was identified in Drosophila melanogaster. Functional studies in Xenopus oocytes showed that INDY mediates the flux of dicarboxylates and citrate across the plasma membrane, but the specific transport mechanism mediated by INDY was not identified. To test whether INDY functions as an anion exchanger, we examined whether substrate efflux is stimulated by transportable substrates added to the external medium. Efflux of [14C]citrate from INDY-expressing oocytes was greatly accelerated by the addition of succinate to the external medium, indicating citrate-succinate exchange. The succinate-stimulated [14C]citrate efflux was sensitive to inhibition by DIDS (4,4'-di-isothiocyano-2,2'-disulphonic stilbene), as demonstrated previously for INDY-mediated succinate uptake. INDY-mediated efflux of [14C]citrate was also stimulated by external citrate and oxaloacetate, indicating citrate-citrate and citrate-oxaloacetate exchange. Similarly, efflux of [14C]succinate from INDY-expressing oocytes was stimulated by external citrate, alpha-oxoglutarate and fumarate, indicating succinate-citrate, succinate-alpha-oxoglutarate and succinate-fumarate exchange respectively. Conversely, when INDY-expressing Xenopus oocytes were loaded with succinate and citrate, [14C]succinate uptake was markedly stimulated, confirming succinate-succinate and succinate-citrate exchange. Exchange of internal anion for external citrate was markedly pH(o)-dependent, consistent with the concept that citrate is co-transported with a proton. Anion exchange was sodium-independent. We conclude that INDY functions as an exchanger of dicarboxylate and tricarboxylate Krebs-cycle intermediates. The effect of decreasing INDY activity, as in the long-lived Indy mutants, may be to alter energy metabolism in a manner that favours lifespan extension.

Involvement of the TTX-resistant sodium channel Nav 1.8 in inflammatory and neuropathic, but not post-operative, pain states.

Antisense (AS) oligodeoxynucleotides (ODNs) targeting the Nav 1.8 sodium channel have been reported to decrease inflammatory hyperalgesia and L5/L6 spinal nerve ligation-induced mechanical allodynia in rats. The present studies were conducted to further characterize Nav 1.8 AS antinociceptive profile in rats to better understand the role of Nav 1.8 in different pain states. Consistent with earlier reports, chronic intrathecal Nav 1.8 AS, but not mismatch (MM), ODN decreased TTX-resistant sodium current density (by 60.5+/-10.2% relative to MM; p<0.05) in neurons from L4 to L5 dorsal root ganglia and significantly attenuated mechanical allodynia following intraplantar complete Freund's adjuvant. In addition, 10 days following chronic constriction injury of the sciatic nerve, Nav 1.8 AS, but not MM, ODN also attenuated mechanical allodynia (54.3+/-8.2% effect, p<0.05 vs. MM) 2 days after initiation of ODN treatment. The anti-allodynic effects remained for the duration of the AS treatment, and CCI rats returned to an allodynic state 4 days after discontinuing AS. In contrast, Nav 1.8 AS ODN failed to reduce mechanical allodynia in the vincristine chemotherapy-induced neuropathic pain model or a skin-incision model of post-operative pain. Finally, Nav 1.8 AS, but not MM, ODN treatment produced a small but significant attenuation of acute noxious mechanical sensitivity in naïve animals (17.6+/-6.2% effect, p<0.05 vs. MM). These data demonstrate a greater involvement of Nav 1.8 in frank nerve injury and inflammatory pain as compared to acute, post-operative or chemotherapy-induced neuropathic pain states.

Inhibition of persistent sodium current fraction and voltage-gated L-type calcium current by propofol in cortical neurons: implications for its antiepileptic activity.

PURPOSE: Although it is widely used in clinical practice, the mechanisms of action of 2,6-di-isopropylphenol (propofol) are not completely understood. We examined the electrophysiologic effects of propofol on an in vitro model of epileptic activity obtained from a slice preparation. METHODS: The effects of propofol were tested both on membrane properties and on epileptiform events consisting of long-lasting, paroxysmal depolarization shifts (PDSs) induced by reducing the magnesium concentration from the solution and by adding bicuculline and 4-aminopyridine. These results were integrated with a patch-clamp analysis of Na(+) and high-voltage activated (HVA) calcium (Ca(2+)) currents from isolated cortical neurons. RESULTS: In bicuculline, to avoid any interference by gamma-aminobutyric acid (GABA)-A receptors, propofol (3-100 microM) did not cause significant changes in the current-evoked, sodium (Na(+))-dependent action-potential discharge. However, propofol reduced both the duration and the number of spikes of PDSs recorded from cortical neurons. Interestingly, relatively low concentrations of propofol [half-maximal inhibitory concentration (IC(50)), 3.9 microM) consistently inhibited the "persistent" fraction of Na(+) currents, whereas even high doses (< or =300 microM) had negligible effects on the "fast" component of Na(+) currents. HVA Ca(2+) currents were significantly reduced by propofol, and the pharmacologic analysis of this effect showed that propofol selectively reduced L-type HVA Ca(2+) currents, without affecting N or P/Q-type channels. CONCLUSIONS: These results suggest that propofol modulates neuronal excitability by selectively suppressing persistent Na(+) currents and L-type HVA Ca(2+) conductances in cortical neurons. These effects might cooperate with the opening of GABA-A-gated chloride channels, to achieve depression of cortical activity during both anesthesia and status epilepticus.

Radial transport of water and abscisic acid (ABA) in roots of Zea mays under conditions of nutrient deficiency.

Radial water (J(V)) and abscisic acid (ABA) flows (J(ABA)) through maize root seedlings have been investigated under different conditions of nutrient deficiency. Whereas J(V) was reduced under nitrogen deficiency, potassium deficiency stimulated J(V). A substantial increase of J(ABA) was observed in roots kept under potassium deficiency. The observed changes of J(V) might have resulted from changed barrier properties of the endodermis. Nitrogen and potassium deficiency also caused an accumulation of endogenous ABA in root tissues. Under all conditions studied, except under K(+)-deficiency, external ABA (100 nM) caused an increase of J(V). The data of this study were used to analyse the relations between internal and endogenous root ABA, J(V), and J(ABA). The internal ABA of root tissues was positively correlated with J(V) and was highly significant (P <0.001 for internal and P=0.03 for endogenous root ABA) within the range 2-300 pmol g(-1) FW. It was also highly positively correlated to the radial ABA flows. There was also a highly positive correlation between J(V) and J(ABA). The data of this study indicate, for the first time, the relations between internal ABA, water, and ABA flows. Independent of treatment with external ABA, an ABA transport by solvent drag across the endodermis is confirmed.

Molecular and functional characterisation of glutamate transporters in rat cortical astrocytes exposed to a defined combination of growth factors during in vitro differentiation.

In vitro culture of astroglial progenitors can be obtained from early post-natal brain tissues and several methods have been reported for promoting their maturation into differentiated astrocytes. Hence, a combination of several nutriments/growth factors -- the G5 supplement (insulin, transferrin, selenite, biotin, hydrocortisone, fibroblast growth factor and epidermal growth factor) -- is widely used as a culture additive favouring the growth, differentiation and maturation of primary cultured astrocytes. Considering the key role played by glial cells in the clearance of glutamate in the synapses, cultured astrocytes are frequently used as a model for the study of glutamate transporters. Indeed, it has been shown that when tested separately, growth factors influence the expression and activity of the GLAST and GLT-1. The present study aimed at characterising the functional expression of these transporters during the time course of differentiation of cultured cortical astrocytes exposed to the supplement G5. After a few days, the vast majority of cells exposed to this supplement adopted a typical stellate morphology (fibrous or type II astrocytes) and showed intense expression of the glial fibrillary acidic protein. Both RT-PCR and immunoblotting studies revealed that the expression of both GLAST and GLT-1 rapidly increased in these cells. While this was correlated with a significant increase in specific uptake of radiolabelled aspartate, fluorescence monitoring of the Na+ influx associated with glutamate transporters activity revealed that the exposure to the G5 supplement considerably increased the percentage of cells participating in the uptake. Biochemical and pharmacological studies revealed that this activity did not involve GLT-1 but most likely reflected an increase in GLAST-mediated uptake. Together, these data indicate that the addition of this classical combination of growth factors and nutriments drives the rapid differentiation toward a homogenous culture of fibrous astrocytes expressing functional glutamate transporters.

Tissue-specific modes of Na/Ca exchanger regulation.

Ionic regulation of Na(+)/Ca(2+) exchange describes the secondary modulating effects exerted on exchange activity by the transport substrates Na(+) and Ca(2+). These effects have been extensively characterized for the cardiac Na(+)/Ca(2+) exchanger, NCX1.1, primarily by the giant excised patch-clamp technique. Moreover, several studies have provided functional evidence for ionic regulation of Na(+)/Ca(2+) exchange activity in intact cellular systems. Through structure-function analyses, important protein domains involved in these regulatory processes have been identified. However, despite major progress in characterizing ionic regulation at the functional and molecular levels, the physiological importance of these processes remains unknown. In this study, we have examined Na(+)/Ca(2+) exchange activity for three members of the NCX1 family, namely NCX1.1, NCX1.3, and NCX1.4. These exchangers were expressed in Xenopus laevis oocytes and were characterized using the giant excised patch-clamp technique. We show that these three splice variants exhibit considerable differences in the kinetic features of their ionic regulatory profiles. Information of this type is beginning to provide insight into the physiological basis for tissue-specific expression of alternatively spliced Na(+)/Ca(2+) exchangers.

The involvement of sodium and calcium ions in the release of amino acid neurotransmitters from mouse cortical slices elicited by hyperforin.

Hyperforin is currently considered to be the major active antidepressant constituent of the medicinal herb St. John's wort (Hypericum perforatum L.). The mechanism of action however, is still largely unknown, although the involvement of sodium and calcium has been recently inferred. In the present study hyperforin (5 microM) significantly potentiated the release of endogenous aspartate and glutamate from mouse cortical slices when stimulated by veratridine or potassium. Hyperforin (5 microM) also stimulated the release of aspartate, glutamate, serine, glycine and GABA when perfused on its own. Perfusion of the sodium channel blocker, tetrodotoxin (TTX) inhibited the effect of hyperforin, whereas removal of extracellular calcium potentiated the effect. Our observations suggests that hyperforin increases the overflow of neurotransmitters from mouse cerebral cortex possibly through facilitating the entry of sodium into the neurone which leads to the release of calcium from intracellular stores.

Acute sodium deficit triggers plasticity of the brain angiotensin type 1 receptors.

The brain renin-angiotensin system (bRAS) is involved in the control of hydromineral balance. However, little information is available on the functional regulation of the bRAS as a consequence of sodium deficit in the extracellular fluid compartments. We used a pharmacological model of acute Na+ depletion (furosemide injections) to investigate changes of a major component of the bRAS, the hypothalamic angiotensin type 1A (AT(1A)) receptors. Furosemide induced a rapid and long-lasting expression of the AT(1A) mRNA in the subfornical organ, the median preoptic nucleus (MnPO), and the parvocellular division of the paraventricular nucleus (pPVN). Na+ depletion increased the number of cells expressing AT(1A) mRNA in the pPVN, but not in the MnPO. The enhancement of AT(1A) mRNA expression was associated with an increase in AT(1) binding sites in all the regions studied. It is of interest that in the paraventricular nucleus, the majority of the neurons expressing AT(1A) mRNA also showed an increase in metabolic activity (Fos-related antigen immunoreactivity [FRA-ir]). By contrast, in the MnPO, we observe two distinct cell populations. Our data demonstrated that an acute Na+ deficit induced a functional regulation of the hypothalamic AT(1A) receptors, indicating that these receptors are subject to plasticity in response to hydromineral perturbations.

[Relationship between enhanced anoxic tolerance induced by hypoxic preconditioning and Na+, K+ currents in cultured hypothalamic cells].

AIM: To investigate the relationship between enhanced anoxic tolerance induced by hypoxic preconditioning and Na+, K+ currents. METHODS: After hypoxic preconditioning and acute anoxia the I(Na), I(K) were measured in cultured hypothalamic cells by patch-clamp whole cell recording technique. RESULTS: The amplification of Na+ currents did not been significantly changed, but the amplification of K+ currents was in hypoxic preconditioning neurons; acute anoxia lead to the inhibition of Na+, K+ currents in the two groups, while Na+, K+ currents in non-preconditioned control group were inhibited severity than hypoxic preconditioning group. CONCLUSION: It is presumed enhanced anoxia tolerance induced by hypoxic preconditioning may be related to the opening of K+ channels.

Time course studies on the effectiveness of tetrodotoxin in reducing consequences of spinal cord contusion.

Focal injection of the sodium channel blocker tetrodotoxin (TTX) into the injury site at either 5 or 15 min after a standardized thoracic contusion spinal cord injury (SCI) reduces white matter pathology and loss of axons in the first 24 hr after injury. Focal injection of TTX at 15 min after SCI also reduces chronic white matter loss and hindlimb functional deficits. We have now tested the hypothesis that the reduction in chronic deficits with TTX treatment is associated with long-term preservation of axons after SCI and compared both acute (24 hr) and chronic (6 weeks) effects of TTX administered at 15 min prior to and 5 min or 4 hr after SCI. Our results indicate a significant reduction of acute white matter pathology in rats treated with TTX at 15 min before and 5 min after injury but no effect when treatment was delayed until 4 hr after contusion. Compared with injury controls, groups treated with TTX at 5 min and 4 hr after injury did not show a significant deficit reduction, nor was there a significant sparing of white matter at 6 weeks compared with injury controls. In contrast, the group treated with TTX at 15 min before SCI demonstrated significantly reduced hindlimb functional deficits beginning at 1 week after injury and throughout the 6 weeks of the study. This was associated with a significantly higher axon density in the ventromedial white matter at 6 weeks. The results demonstrate that blockade of sodium channels preserves axons from loss after SCI and points to the importance of time of administration of such drugs for therapeutic effectiveness.

Dietary psyllium increases expression of ileal apical sodium-dependent bile acid transporter mRNA coordinately with dose-responsive changes in bile acid metabolism in rats.

Psyllium (PSY), a type of dietary fiber containing mainly soluble components, has been shown to decrease serum cholesterol concentrations in several species; however, mechanisms involved are not clearly defined. Four groups of 10 rats were fed semipurified diets containing 10% dietary fiber from cellulose and/or PSY for 21 d. Increasing levels of PSY were fed (0,3.33, 6.67 and 10% PSY) with the remaining 10% made up with cellulose. Liver cholesterol, cholesterol 7alpha-hydroxylase (CYP7A) activity and mRNA, 3-hydroxy-3-methylglutaryl CoA reductase (HMGR) mRNA, ileal apical sodium-dependent bile acid transporter (ASBT) mRNA, fecal bile acids and total steroids, and intestinal bile acid content were measured. All variables responded in a dose-dependent manner to PSY in the diet. Total liver cholesterol content was significantly reduced in all groups fed PSY compared to cellulose-fed controls [138(a), 105(b), 105(b) and 93(c) micromol (SEM = 4.2) for 0, 3.33, 6.67 and 10% PSY, respectively]. Activity of CYP7A was significantly greater in all groups fed PSY compared to the cellulose-fed controls [6.36(c), 16.92(b), 15.28(b) and 20.37(a) pmol x min(-1) x mg protein(-1) (SEM = 3.19) for 0, 3.33, 6.67 and 10% PSY, respectively]. These differences in CYP7A activity were similar to differences in CYP7A, HMGR and ASBT mRNA levels. Fecal bile acid and total steroid excretion as well as total intestinal bile acids were significantly greater in rats fed PSY-containing diets compared to 0% PSY-fed rats. These results suggest that the reduction in liver cholesterol involves modulating the size and composition of the bile acid pool via regulation of ileal ASBT, CYP7A and HMGR mRNA levels.