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Tubular Cells (tubular + cell)

Distribution by Scientific Domains
Medical Sciences70%
Life Sciences20%
Chemistry6%
Distribution within Medical Sciences
Pharmacology & Pharmaceutical Medicine8%
Pathology5%

Kinds of Tubular Cells

  • proximal tubular cell
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  • renal proximal tubular cell
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  • renal tubular cell
    		•

    Terms modified by Tubular Cells

  • tubular cell injury
    		•

    Selected Abstracts

    FAS LIGAND TRANSFECTION OF RENAL TUBULAR CELLS INDUCES APOPTOSIS OF ACTIVATED LEUCOCYTES

    NEPHROLOGY, Issue 3 2000
    Wang Yp
    [source]

    Epithelial to Mesenchymal Transition During Late Deterioration of Human Kidney Transplants: The Role of Tubular Cells in Fibrogenesis

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2005
    Attapong Vongwiwatana
    The hallmark of failing renal transplants is tubular atrophy and interstitial fibrosis (TA/IF). Injury to tubular epithelial cells (TEC) could contribute to fibrogenesis via epithelial,mesenchymal transition (EMT). We examined the features of EMT in renal transplants that developed TA/IF. Biopsies from 10 allograft kidneys with impaired function and TA/IF and 10 biopsies from transplants with stable function were compared to their implantation biopsies. Relative to implantation biopsies, TEC in TA/IF kidneys showed loss of epithelial markers (E-cadherin, cytokeratin) with altered distribution. Some TEC also showed new cytoplasmic expression of mesenchymal markers vimentin, S100A4, and alpha smooth muscle actin (,-SMA) and collagen synthesis marker heat shock protein (HSP-47), both in deteriorating and atrophic tubules. Double immunostaining showed coexpression of cytokeratin and vimentin, S100A4 and HSP-47, indicating intermediate stages of EMT in TA/IF. These changes were absent or much less in transplants with stable function. EMT features in the TA/IF group correlated with serum creatinine (vimentin, S100A4, HSP-47), history of T-cell-mediated rejection (cytokeratin, S100A4) and proteinuria (cytokeratin). These findings support a model in which the TEC damage induces loss of epithelial features and expression of fibroblast features, as a common pathway of deterioration by either immunologic or nonimmunologic processes. [source]

    Prediction of human pharmacokinetics , renal metabolic and excretion clearance

    JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 11 2007
    Urban Fagerholm
    The kidneys have the capability to both excrete and metabolise drugs. An understanding of mechanisms that determine these processes is required for the prediction of pharmacokinetics, exposures, doses and interactions of candidate drugs. This is particularly important for compounds predicted to have low or negligible non-renal clearance (CL). Clinically significant interactions in drug transport occur mostly in the kidneys. The main objective was to evaluate methods for prediction of excretion and metabolic renal CL (CLR) in humans. CLR is difficult to predict because of the involvement of bi-directional passive and active tubular transport, differences in uptake capacity, pH and residence time on luminal and blood sides of tubular cells, and limited knowledge about regional tubular residence time, permeability (Pe) and metabolic capacity. Allometry provides poor predictions of excretion CLR because of species differences in unbound fraction, urine pH and active transport. The correlation between fraction excreted unchanged in urine (fe) in humans and animals is also poor, except for compounds with high passive Pe (extensive/complete tubular reabsorption; zero/negligible fe) and/or high non-renal CL. Physiologically based in-vitro/in-vivo methods could potentially be useful for predicting CLR. Filtration could easily be predicted. Prediction of tubular secretion CL requires an in-vitro transport model and establishment of an in-vitro/in-vivo relationship, and does not appear to have been attempted. The relationship between passive Pe and tubular fraction reabsorbed (freabs) for compounds with and without apparent secretion has recently been established and useful equations and limits for prediction were developed. The suggestion that reabsorption has a lipophilicity cut-off does not seem to hold. Instead, compounds with passive Pe that is less than or equal to that of atenolol are expected to have negligible passive freabs. Compounds with passive Pe that is equal to or higher than that of carbamazepine are expected to have complete freabs. For compounds with intermediate Pe the relationship is irregular and freabs is difficult to predict. Tubular cells are comparably impermeable (for passive diffusion), and show regional differences in enzymatic and transporter activities. This limits the usefulness of microsome data and makes microsome-based predictions of metabolic CLR questionable. Renal concentrations and activities of CYP450s are comparably low, suggesting that CYP450 substrates have negligible metabolic CLR. The metabolic CLR of high-Pe UDP-glucuronyltransferase substrates could contribute to the total CL. [source]

    BK Polyoma Virus Allograft Nephropathy: Ultrastructural Features from Viral Cell Entry to Lysis

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2003
    Cinthia B Drachenberg
    BK virions must enter the host cell and target their genome to the nucleus in order to complete their life cycle. The mechanisms by which the virions accomplish these tasks are not known. In this morphological study we found that BK virions localized beneath the host cell cytoplasmic membrane in 60,70-nm, smooth (non-coated) monopinocytotic vesicles similar to, or consistent with, caveolae. In the cytoplasm, the monopinocytotic vesicles carrying virions appeared to fuse with a system of smooth, vesicles and tubules that communicated with the rough endoplasmic reticulum and was continuous with the Golgi system. Membrane-bound single virions and large tubulo-reticular complexes loaded with virions accumulated in paranuclear locations. Occasional nuclei displayed virions within the perinuclear cisterna in association to the perinuclear viral accumulations. Tubular cells with mature productive infection had large nuclei, distended by daughter virions, whereas they lacked significant numbers of cytoplasmic virions. In addition to virally induced cell necrosis, there was extensive tubular cell damage (apoptosis and necrosis) in morphologically non-infected tubules. The observed ultrastructural interactions between the BK virions and host cells are remarkably similar to viral cell entry and nuclear targeting described for SV40 virus. [source]

    Fabrication and Characterization of Anode-Supported Tubular Solid-Oxide Fuel Cells by Slip Casting and Dip Coating Techniques

    JOURNAL OF THE AMERICAN CERAMIC SOCIETY, Issue 2 2009
    Lan Zhang
    High-performance anode-supported tubular solid-oxide fuel cells (SOFCs) have been successfully developed and fabricated using slip casting, dip coating, and impregnation techniques. The effect of a dispersant and solid loading on the viscosity of the NiO/Y2O3,ZrO2 (NiO/YSZ) slurry is investigated in detail. The viscosity of the slurry was found to be minimum when the dispersant content was 0.6 wt% of NiO/YSZ. The effect of sintering temperature on the shrinkage and porosity of the anode tubes, densification of the electrolyte, and performance of the cell at different solid loadings is also investigated. A Ni/YSZ anode-supported tubular cell fabricated from the NiO/YSZ slurry with 65 wt% solid loading and sintered at 1380°C produced a peak power output of ,491 and ,376 mW/cm2 at 800°C in wet H2 and CH4, respectively. With the impregnation of Ce0.8Gd0.2O2 (GDC) nanoparticles, the peak power density increased to ,1104 and ,770 mW/cm2 at 800°C in wet H2 and CH4, respectively. GDC impregnation considerably enhances the electrochemical performance of the cell and significantly reduces the ohmic and polarization resistances of thin solid electrolyte cells. [source]

    Perinatal development of the rat kidney: Apoptosis and epidermal growth factor

    CONGENITAL ANOMALIES, Issue 3 2003
    Toshiya Okada
    ABSTRACT, Localization of apoptotic cells in the kidney of perinatal rats was examined by the terminal deoxynucleotidyl transferase,mediated d,UTP,biotin nick end labeling (TUNEL) method and electron microscopy. Perinatal changes in the percentage of kidney cells with DNA fragmentation were determined by flow cytometric analysis. Through observation of two successive sections, the relationship between the localization of the epidermal growth factor receptor (EGFR) positive cells and TUNEL positive cells in the kidney was determined. From fetal day 18 to neonatal day 5, TUNEL positive cells were noted in immature glomeruli, collecting ducts and interstitium. Electron microscopically, chromatin condensed nuclei and apoptotic bodies were seen in the same tissue component as the TUNEL positive cells. The percentage of DNA fragmented cells significantly increased from fetal days 18 to 20 and significantly decreased from fetal days 20 to 22, while they still remained low in the neonatal period. The TUNEL positive cells in immature glomeruli and collecting ducts were not reactive to the EGFR antibody. The TUNEL positive cells were not observed in the proximal tubular cells, which were positive to EGFR antibody. These results indicate that apoptotic cells are present in the kidney throughout the perinatal period in the rat and that EGF plays an important role in perinatal development of the rat kidney. [source]

    TRAF6 knockdown promotes survival and inhibits inflammatory response to lipopolysaccharides in rat primary renal proximal tubule cells

    ACTA PHYSIOLOGICA, Issue 3 2010
    S. Liu
    Abstract Aim:, TRAF6 is a unique adaptor protein of the tumour necrosis factor receptor-associated factor family that mediates both tumour necrosis factor receptor (TNFR) and interleukin-1 receptor/Toll-like receptor (IL-1R/TLR) signalling. Activation of IL-1R/TLR and TNFR pathways in renal tubular cells contributes to renal injury. This study aimed to investigate if blockade of lipopolysaccharide (LPS)-triggered TLR4 signalling by small interfering RNA (siRNA) targeting TRAF6 protects survival and inhibits inflammatory response in isolated rat renal proximal tubular cells (PTCs). Methods:, PTCs isolated from F344 rat kidneys were transfected with chemically synthesized siRNA targeting TRAF6 mRNA. Real-time quantitative PCR was applied to measure mRNA level of TRAF6, TNF-,, IL-6 and monocyte chemoattractant protein-1 (MCP-1). Protein levels of extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase, caspase 3 and cleaved caspase 3 were evaluated by Western blotting. Cell viability was analysed with XTT reagents. Results:, We found that the TRAF6 gene was effectively silenced in PTCs using siRNA. TRAF6 knockdown resulted in reduced TNF-, and IL-6 mRNA expression upon LPS challenge. LPS-induced phosphorylation of JNK and p38 was attenuated in TRAF6 siRNA-transfected cells while the change in the phosphorylation of ERK was not remarkable. TRAF6 knockdown was associated with increased cell viability and reduced protein level of cleaved caspase-3, both, in the absence and presence of LPS. Conclusion:, Our studies suggest that TRAF6 knockdown may inhibit inflammatory response and promote cell survival upon LPS challenge in primary rat proximal renal tubular cells. [source]

    Urine cytology in renal glomerular disease and value of G1 cell in the diagnosis of glomerular bleeding

    DIAGNOSTIC CYTOPATHOLOGY, Issue 2 2003
    Gia-Khanh Nguyen M.D.
    Abstract The objectives of the present study were to evaluate the cytology of urine sediments in patients with glomerular diseases, as well as the value of G1 dysmorphic erythrocytes (G1DE) or G1 cells in the detection of renal glomerular hematuria. Freshly voided urine samples from 174 patients with glomerular diseases were processed according to the method used for semiquantitative cytologic urinalysis. G1DEs (distorted erythrocytes with doughnut-like shape, target configuration with or without membranous protrusions or blebs), non-G1DEs (distorted erythrocytes without the above-mentioned morphologic changes), normal erythrocytes (NEs), and renal tubular cells (RTCs) were evaluated. Erythrocytic casts (ECs) were counted and graded as abundant (>1 per high-power field) or rare (1 per 5 high-power fields). G1DE/total erythrocyte ratios were calculated by counting 200 erythrocytes including G1DEs, non-G1DEs, and NEs. Only abundant NEs were found in 13 cases; abundant G1DEs, non-G1DEs, NEs, and no ECs in 95 cases; abundant NEs, non-G1DEs, and ECs and no G1DEs in 31 cases; and abundant NEs, G1DEs and non-G1DEs, and rare ECs in 35 cases. In 130 cases in which G1DEs were present, the G1DE/total erythrocyte ratios varied from 10% to 100%. This parameter was greater or equal to 80%, 50%, 20%, and 10% in 58 (44.6%), 29 (22.3%), 28 (21.5%), and 15 (11.5%) patients, respectively. In all cases, the number of RTCs was within normal limits or slightly increased, and a variable number of non-G1DEs were present in 161 cases. Thus, abundant ECs and/or G1DEs with a G1DE/total erythrocyte ratio of 10,100% proved to be specific urinary markers for renal glomerular diseases. Diagn. Cytopathol. 2003;29:67,73. © 2003 Wiley-Liss, Inc. [source]

    Effect of capsaicin on Ca2+ fluxes in Madin-Darby canine renal tubular cells

    DRUG DEVELOPMENT RESEARCH, Issue 2 2010
    Jeng-Hsien Yeh
    Abstract The effect of capsaicin, a transient receptor potential vanniloid-1 (TRPV1) receptor agonist, on cytosolic free Ca2+ concentrations ([Ca2+]i) in Madin Darby canine kidney (MDCK) cells is unclear. This study explored whether capsaicin changed basal [Ca2+]i levels in suspended MDCK cells by using fura-2 as a Ca2+ -sensitive fluorescent dye. Capsaicin at concentrations between 10,100,µM increased [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced by 80% by removing extracellular Ca2+. Capsacin induced Mn2+ influx, leading to quench of fura-2 fluorescence suggesting Ca2+ influx. This Ca2+ influx was inhibited by phospholipase A2 inhibitor aristolochic acid and the non-selective Ca2+ entry blocker La3+, but not by store-operated Ca2+ channel blockers nifedipine, econazole, and SK&F96365, and protein kinase C/A modulators. In Ca2+ -free medium, pretreatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin abolished capsaicin-induced Ca2+ release. Conversely, pretreatment with capsaicin partly reduced thapsigargin-induced [Ca2+]i rise. Inhibition of phospholipase C with U73122 did not alter capsaicin-induced [Ca2+]i rise. The TRPV1 receptor antagonist capsazepine also induced significant Ca2+ entry and Ca2+ release. Collectively, in MDCK cells, capsaicin induced [Ca2+]i rises by causing phospholipase C-independent Ca2+ release from the endoplasmic reticulum and Ca2+ influx via phospholipase A2-regulated, La3+ -sensitive Ca2+ channels in a manner dissociated from stimulation of TRPV1 receptors. Drug Dev Res, 2009. © 2009 Wiley-Liss, Inc. [source]

    Nonylphenol-induced cytosolic Ca2+ elevation and death in renal tubular cells

    DRUG DEVELOPMENT RESEARCH, Issue 5 2009
    Jeng-Yu Tsai
    Abstract Nonylphenol is an environmental endocrine disrupter. The effect of nonylphenol on intracellular free Ca2+ levels ([Ca2+]i) and viability in Madin-Darby canine kidney (MDCK) cells was explored. Nonylphenol increased [Ca2+]i in a concentration-dependent manner (EC50,0.8,,M). Nonylphenol-induced Mn2+ entry demonstrated Ca2+ influx and removal of extracellular Ca2+ partly decreased the [Ca2+]i rise. The [Ca2+]i rise was inhibited by the protein kinase C activator, phorbol 13-myristate acetate (PMA) but not by L-type Ca2+ channel blockers. In Ca2+ -free medium, nonylphenol-induced [Ca2+]i rise was partly inhibited by pretreatment with 1,,M thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor). Conversely, nonylphenol pretreatment abolished thapsigargin-induced Ca2+ release. Nonylphenol-induced Ca2+ release was unaltered by inhibition of phospholipase C. At concentrations of 5,100,,M, nonylphenol killed cells in a concentration-dependent manner. The cytotoxic effect of 100,,M nonylphenol was not affected by preventing [Ca2+]i rises with BAPTA/AM. Collectively, this study shows that nonylphenol induced [Ca2+]i increase in MDCK cells via evoking Ca2+ entry through protein kinase C-regulated Ca2+ channels, and releasing Ca2+ from endoplasmic reticulum and other stores in a phospholipase C-independent manner. Nonylphenol also killed cells in a Ca2+ -independent fashion. Drug Dev Res, 2009. © 2009 Wiley-Liss, Inc. [source]

    Lysosomal storage disease in Sida carpinifolia toxicosis: an induced mannosidosis in horses

    EQUINE VETERINARY JOURNAL, Issue 5 2003
    A. P. LORETTI
    Summary Reasons for performing study: This study reports a neurological disease unrecognised until now in ponies in southern Brazil. Hypothesis: Epidemiological data strongly suggests that the ingestion of Sida carpinifolia is involved in the aetiology. We tested the hypothesis that it is an acquired lyosomal storage disease. Methods: Following the death of 3 ponies, all ponies from the premises were closely monitored; epidemiological data and clinical findings carefully recorded. Fragments of several organs, including CNS, were fixed in neutral formalin and embedded in paraffin-wax. Sections were stained with haematoxylin and eosin. Representative sections of the cerebellum and trigeminal ganglia were submitted to lectin histochemical procedures. Results: The neurological disorder, characterised by stiff gait, muscle tremors, abdominal pain and death, was observed on a farm with 3 hectares of pasture. Three of 11 ponies died 15,20 days after they had been introduced into a new paddock heavily infested by the plant Sida carpinifolia. No significant gross lesions were observed. The main histological findings included multiple cytoplasmatic vacuoles in swollen neurones in the brain, cerebellum, spinal cord, autonomic ganglia (trigeminal and celiac ganglia), and submucosal and myenteric plexus of the intestines. In the kidneys, there was marked vacuolation of the proximal convoluted tubular cells. Sections of cerebellum and trigeminal ganglion were submitted to lectin histochemistry. The vacuoles in different cerebellar and ganglion cells reacted strongly to the following lectins: Concanavalia ensiformis, Triticum vulgaris and succinylated- Triticum vulgaris. Conclusions: The pattern of staining coincides with that of both swainsonine toxicosis and inherited mannosidosis reports. The histopathological changes were similar to those described in S. carpinifolia spontaneous and experimental poisoning in goats. This disease seems to be similar to Swainsona, Oxytropis and Astragalus toxicosis. Potential relevance: S. carpinifolia should be evaluated as a possible cause in the diagnosis of equine neuropathies. [source]

    From kidney to cardiovascular diseases: NGAL as a biomarker beyond the confines of nephrology

    EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 3 2010
    D. Bolignano
    Eur J Clin Invest 2010; 40 (3): 273,276 Abstract Neutrophil gelatinase-associated lipocalin (NGAL), a small 25 kDa stress-protein released from injured tubular cells after various damaging stimuli, is already known by nephrologists as one of the most promising biomarkers of incoming Acute Kidney Injury. Moreover, recent studies seem to suggest a potential involvement of this factor also in the genesis and progression of chronic kidney diseases. This brief review explores the new interesting involvement of NGAL in the experimental and clinical field of cardiovascular diseases, such as the pathogenesis and clinical manifestations of atherosclerosis, acute myocardial infarction and heart failure. It does not seem difficult that, in the next future, NGAL may become a new missing link between the kidney and the cardiovascular system. [source]

    De novo synthesis, uptake and proteolytic processing of lipocalin-type prostaglandin D synthase, ,-trace, in the kidneys

    FEBS JOURNAL, Issue 23 2009
    Nanae Nagata
    Lipocalin-type prostaglandin D synthase (L-PGDS) is a multifunctional protein that produces prostaglandin D2 and binds and transports various lipophilic substances after secretion into various body fluids as ,-trace. L-PGDS has been proposed to be a useful diagnostic marker for renal injury associated with diabetes or hypertension, because the urinary and plasma concentrations are increased in patients with these diseases. However, it remains unclear whether urinary L-PGDS is synthesized de novo in the kidney or taken up from the blood circulation. In crude extracts of monkey kidney and human urine, we found L-PGDS with its original N-terminal sequence starting from Ala23 after the signal sequence, and also its N-terminal-truncated products starting from Gln31 and Phe34. In situ hybridization and immunohistochemical staining with monoclonal antibody 5C11, which recognized the amino-terminal Ala23,Val28 loop of L-PGDS, revealed that both the mRNA and the intact form of L-PGDS were localized in the cells of Henle's loop and the glomeruli of the kidney, indicating that L-PGDS is synthesized de novo in these tissues. However, truncated forms of L-PGDS were found in the lysosomes of tubular cells, as visualized by immunostaining with 10A5, another monoclonal antibody, which recognized the three-turn ,-helix between Arg156 and Thr173. These results suggest that L-PGDS is taken up by tubular cells and actively degraded within their lysosomes to produce the N-terminal-truncated form. Structured digital abstract ,,MINT-7266187: L-PGDS (uniprotkb:P41222) and Cathepsin D (uniprotkb:Q4R4P0) colocalize (MI:0403) by fluorescence microscopy (MI:0416) ,,MINT-7266176: L-PGDS (uniprotkb:P41222) and Cathepsin B (uniprotkb:Q4R5M2) colocalize (MI:0403) by fluorescence microscopy (MI:0416) [source]

    New Stack Design of Micro-tubular SOFCs for Portable Power Sources

    FUEL CELLS, Issue 6 2008
    T. Suzuki
    Abstract Micro-tubular solid oxide fuel cells (SOFCs) have high thermal stability and higher volumetric power density, which are considered to be ideal features for portable power sources and auxiliary power units for automobile. Here, we report a new stack design using anode supported micro-tubular SOFCs with 2,mm diameter using Gd doped CeO2 (GDC) electrolyte, NiO-GDC anode and (La, Sr)(Co, Fe)O3 (LSCF)-GDC cathode. The new stack consists of three bundles with five tubular cells, sealing layers and interconnects and fuel manifolds. The performance of the stack whose volume is 1,cm3 was shown to be 2.8,V OCV and maximum power output of 1.5,W at 500,°C, applying air only by natural convection. The results also showed strong dependence of the fuel flow rates on the stack performance, which was correlated to the gas diffusion limitation. [source]

    Fibroblast growth factor 23 reduces expression of type IIa Na+/Pi co-transporter by signaling through a receptor functionally distinct from the known FGFRs in opossum kidney cells

    GENES TO CELLS, Issue 5 2005
    Xiaomei Yan
    Fibroblast growth factor (FGF) 23 is an important phosphaturic factor that inhibits inorganic phosphate (Pi) reabsorption from the renal proximal tubule. Its overproduction and proteolysis-resistant mutation such as R179Q cause tumor-induced osteomalacia and autosomal dominant hypophosphatemic rickets, respectively. To clarify the signaling mechanisms of FGF23 that mediate the reduction of Pi reabsorption, we inhibited the function of the known FGFRs in opossum kidney (OK-E) cells by expressing a dominant-negative (DN) form of FGFR. OK-E cells, which represent the renal proximal tubular cells, expressed all four known FGFRs. FGF23(R179Q) bound to and activated FGFR2, a prominent FGFR expressed in OK-E cells. The activated receptor transmitted a signal to increase the expression of type IIa Na+/Pi co-transporter and the Pi uptake. Expression of FGFR2(DN), which suppresses the major FGFR-mediated signal through the FRS2,-ERK pathway, reversed the function of FGF23(R179Q). When FGF23(R179Q) was applied to the basolateral side of polarized OK-E cells, regardless of the FGFR2(DN) expression, the apical Pi uptake decreased significantly. The apical application of FGF23(R179Q) in the polarized cells did not show such decrease but increase. The exogenously expressed FGFR2 was detectable only at the apical membrane. These results suggest that an FGF23 receptor, which is functionally distinct from the known FGFRs, is expressed at the basolateral membrane of OK-E cells. [source]

    Mechanism of calcium oxalate renal stone formation and renal tubular cell injury

    INTERNATIONAL JOURNAL OF UROLOGY, Issue 2 2008
    Masao Tsujihata
    Abstract: Formation of calcium oxalate stones tends to increase with age and begins from the attachment of a crystal formed in the cavity of renal tubules to the surface of renal tubular epithelial cells. Though most of the crystals formed in the cavity of renal tubules are discharged as is in the urine, in healthy people, crystals that attach to the surface of renal tubular epithelial cells are thought to be digested by macrophages and/or lysosomes inside of cells. However, in individuals with hyperoxaluria or crystal urine, renal tubular cells are injured and crystals easily become attached to them. Various factors are thought to be involved in renal tubular cell injury. Crystals attached to the surface of renal tubular cells are taken into the cells (crystal,cell interaction). And then the crystal and crystal aggregates grow, and finally a stone is formed. [source]

    Urinary macromolecules and renal tubular cell protection from oxalate injury: Comparison of normal subjects and recurrent stone formers

    INTERNATIONAL JOURNAL OF UROLOGY, Issue 3 2006
    MASAO TSUJIHATA
    Aim:, To determine whether urinary macromolecules (UMM), which are the high molecular weight substances in urine, can provide protection against the oxalate-associated injury to the renal tubular cells. Methods:, UMM were extracted from 24-h urine of 12 healthy adult male volunteers and 13 recurrent-stone-former male patients. Urine parameters in relation to urolithiasis were measured, including the level of glycosaminoglycans (GAG) in the UMM. Madin-Darby canine kidney (MDCK) cells were used to evaluate the protective activity of UMM from oxalate-induced cytotoxicity by LDH release measurement and methyl-thiazolyl tertrazolium (MTT) assay. Results:, Considering urinary parameters, citrate was significantly higher in urine from normal subjects than stone-former subjects; the other parameters show no differences between the groups. Total UMM and the level of GAG in the UMM were also significantly higher in the normal subject group. Compared with normal subject and stone-former subject UMM, after cells were treated with the UMM and then exposed to oxalate solution, LDH release was significantly higher in stone-former group. In the MTT assay, we found that more viable cells were observed after treatment with UMM compared to control in both groups. Moreover, UMM from the normal subjects showed higher protective activity against oxalate-related cytotoxicity than UMM from the stone-former subjects. Conclusion:, UMM protected renal epithelial cells from oxalate-related injury. This protective activity was found to be higher in normal subject UMM than stone-former UMM. Among other factors, a higher concentration of GAG and citrate in normal subject UMM might affect some parts in this finding. [source]

    Ultrastructure and embryonic development of a syconoid calcareous sponge

    INVERTEBRATE BIOLOGY, Issue 3 2006
    Dafne I. Eerkes-Medrano
    Abstract. Recent molecular data suggest that the Porifera is paraphyletic (Calcarea+Silicea) and that the Calcarea is more closely related to the Metazoa than to other sponge groups, thereby implying that a sponge-like animal gave rise to other metazoans. One ramification of these data is that calcareous sponges could provide clues as to what features are shared among this ancestral metazoan and higher animals. Recent studies describing detailed morphology in the Calcarea are lacking. We have used a combination of microscopy techniques to study the fine structure of Syconcoactum Urban 1905, a cosmopolitan calcareous sponge. The sponge has a distinct polarity, consisting of a single tube with an apically opening osculum. Finger-like chambers, several hundred micrometers in length, form the sides of the tube. The inner and outer layers of the chamber wall are formed by epithelia characterized by apical,basal polarity and occluding junctions between cells. The outer layer,the pinacoderm,and atrial cavity are lined by plate-like cells (pinacocytes), and the inner choanoderm is lined by a continuous sheet of choanocytes. Incurrent openings of the sponge are formed by porocytes, tubular cells that join the pinacoderm to the choanoderm. Between these two layers lies a collagenous mesohyl that houses sclerocytes, spicules, amoeboid cells, and a progression of embryonic stages. The morphology of choanocytes and porocytes is plastic. Ostia were closed in sponges that were vigorously shaken and in sponges left in still water for over 30 min. Choanocytes, and in particular collar microvilli, varied in size and shape, depending on their location in the choanocyte chamber. Although some of the odd shapes of choanocytes and their collars can be explained by the development of large embryos first beneath and later on top of the choanocytes, the presence of many fused collar microvilli on choanocytes may reflect peculiarities of the hydrodynamics in large syconoid choanocyte chambers. The unusual formation of a hollow blastula larva and its inversion through the choanocyte epithelium are suggestive of epithelial rather than mesenchymal cell movements. These details illustrate that calcareous sponges have characteristics that allow comparison with other metazoans,one of the reasons they have long been the focus of studies of evolution and development. [source]

    Dopamine increases renal oxygenation: a clinical study in post-cardiac surgery patients

    ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2010
    BENGT REDFORS
    Background: Imbalance of the renal medullary oxygen supply/demand relationship can cause ischaemic acute renal failure (ARF). The use of dopamine for prevention/treatment of ischaemic ARF has been questioned. It has been suggested that dopamine may increase renal oxygen consumption (RVO2) due to increased solute delivery to tubular cells, which may jeopardise renal oxygenation. Information on the effects of dopamine on renal perfusion, filtration and oxygenation in man is, however, lacking. We evaluated the effects of dopamine on renal blood flow (RBF), glomerular filtration rate (GFR), RVO2 and renal O2 demand/supply relationship, i.e. renal oxygen extraction (RO2Ex). Methods: Twelve uncomplicated, mechanically ventilated and sedated post-cardiac surgery patients with pre-operatively normal renal function were studied. Dopamine was sequentially infused at 2 and 4 ug/kg/min. Systemic haemodynamics were evaluated by a pulmonary artery catheter. Absolute RBF was measured using two independent techniques: by the renal vein thermodilution technique and by infusion clearance of paraaminohippuric acid (PAH), with a correction for renal extraction of PAH. The filtration fraction (FF) was measured by the renal extraction of 51Cr-EDTA. Results: Neither GFR, tubular sodium reabsorption nor RVO2 was affected by dopamine, which increased RBF (45,55%) with both methods, decreased renal vascular resistance (30,35%), FF (21,26%) and RO2Ex (28,34%). The RBF/CI ratio increased with dopamine. Dopamine decreased renal PAH extraction, suggestive of a flow distribution to the medulla. Conclusions: In post-cardiac surgery patients, dopamine increases the renal oxygenation by a pronounced renal pre-and post-glomerular vasodilation with no increases in GFR, tubular sodium reabsorption or renal oxygen consumption. [source]

    Effect of aroclor 1248 and two pure PCB congeners on phospholipase D activity in rat renal tubular cell cultures

    JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 2 2007
    Mercedes Fernández Santiago
    Abstract This paper elucidates the effect of different polychlorinated biphenyls (PCBs) on the phospholipase D (PLD) activity in soluble and particulate fractions of rat renal proximal tubular culture cells. Treatment with Aroclor 1248 (a commercial PCB mixture) caused a marked increase in the activity of PLD in intact renal tubular cells. The PLD activity was increased by Aroclor 1248 in the particulate fraction while the enzyme activity was unaffected in the soluble fraction. This work also shows that PCB 153 (2,2',4,4',5,5'-hexachlorobiphenyl, a di-ortho-substituted nonplanar congener) can increase the activity of PLD only in the particulate fraction. The exposure of cell cultures to PCB 77 (3,3',4,4'-tetrachlorobiphenyl, a non-ortho-substituted planar congener) does not alter PLD activity. These results suggest that PCB effects are structure dependent. Therefore, in order to clarify the molecular mechanism of activation of PLD by PCBs, the contents of immunoreactive PLD were examined by immunoblot analysis. Renal tubular cells expressed a PLD protein of 120 kDa corresponding with the PLD1 mammalian isoform in both the particulate and the soluble fraction. Aroclor 1248, PCB 153, and PCB 77 do not induce changes in the levels of PLD protein. These data indicate that PCBs, particularly nonplanar congeners, increase PLD activity. Moreover, these changes could not be demonstrated in the enzyme content in rat renal tubular cell cultures. © 2007 Wiley Periodicals, Inc. J Biochem Mol Toxicol 21:68,75, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20160 [source]

    Prediction of human pharmacokinetics , renal metabolic and excretion clearance

    JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 11 2007
    Urban Fagerholm
    The kidneys have the capability to both excrete and metabolise drugs. An understanding of mechanisms that determine these processes is required for the prediction of pharmacokinetics, exposures, doses and interactions of candidate drugs. This is particularly important for compounds predicted to have low or negligible non-renal clearance (CL). Clinically significant interactions in drug transport occur mostly in the kidneys. The main objective was to evaluate methods for prediction of excretion and metabolic renal CL (CLR) in humans. CLR is difficult to predict because of the involvement of bi-directional passive and active tubular transport, differences in uptake capacity, pH and residence time on luminal and blood sides of tubular cells, and limited knowledge about regional tubular residence time, permeability (Pe) and metabolic capacity. Allometry provides poor predictions of excretion CLR because of species differences in unbound fraction, urine pH and active transport. The correlation between fraction excreted unchanged in urine (fe) in humans and animals is also poor, except for compounds with high passive Pe (extensive/complete tubular reabsorption; zero/negligible fe) and/or high non-renal CL. Physiologically based in-vitro/in-vivo methods could potentially be useful for predicting CLR. Filtration could easily be predicted. Prediction of tubular secretion CL requires an in-vitro transport model and establishment of an in-vitro/in-vivo relationship, and does not appear to have been attempted. The relationship between passive Pe and tubular fraction reabsorbed (freabs) for compounds with and without apparent secretion has recently been established and useful equations and limits for prediction were developed. The suggestion that reabsorption has a lipophilicity cut-off does not seem to hold. Instead, compounds with passive Pe that is less than or equal to that of atenolol are expected to have negligible passive freabs. Compounds with passive Pe that is equal to or higher than that of carbamazepine are expected to have complete freabs. For compounds with intermediate Pe the relationship is irregular and freabs is difficult to predict. Tubular cells are comparably impermeable (for passive diffusion), and show regional differences in enzymatic and transporter activities. This limits the usefulness of microsome data and makes microsome-based predictions of metabolic CLR questionable. Renal concentrations and activities of CYP450s are comparably low, suggesting that CYP450 substrates have negligible metabolic CLR. The metabolic CLR of high-Pe UDP-glucuronyltransferase substrates could contribute to the total CL. [source]

    Reduction of ciclosporin and tacrolimus nephrotoxicity by plant polyphenols

    JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 11 2006
    Zhi Zhong
    The immunosuppressants ciclosporin (cyclosporin A, CsA) and tacrolimus can cause severe nephrotoxicity. Since CsA increases free radical formation, this study investigated whether an extract from Camellia sinensis, which contains several polyphenolic free radical scavengers, could prevent nephrotoxicity caused by CsA and tacrolimus. Rats were fed powdered diet containing polyphenolic extract (0-0.1%) starting 3 days before CsA or tacrolimus. Free radicals were trapped with ,-(4-pyridyl-1-oxide)- N - tert -butylnitrone (POBN) and measured using an electron spin resonance spectrometer. Both CsA and tacrolimus decreased glomerular filtration rates (GFR) and caused tubular atrophy, vacuolization and calcification and arteriolar hyalinosis, effects that were blunted by treatment with dietary polyphenols. Moreover, CsA and tacrolimus increased POBN/radical adducts in urine nearly 3.5 fold. Hydroxyl radicals attack dimethyl sulfoxide (DMSO) to produce a methyl radical fragment. Administration of CsA or tacrolimus with 12C-DMSO produced a 6-line spectrum, while CsA or tacrolimus given with 13C-DMSO produced a 12-line ESR spectrum, confirming formation of hydroxyl radicals. 4-Hydroxynonenal (4-HNE), a product of lipid peroxidation, accumulated in proximal and distal tubules after CsA or tacrolimus treatment. ESR changes and 4-HNE formation were largely blocked by polyphenols. Taken together, these results demonstrate that both CsA and tacrolimus stimulate free radical production in the kidney, most likely in tubular cells, and that polyphenols minimize nephrotoxicity by scavenging free radicals. [source]

    Melatonin suppresses cyclosporine A-induced autophagy in rat pituitary GH3 cells

    JOURNAL OF PINEAL RESEARCH, Issue 3 2010
    Yeong-Min Yoo
    Abstract:, Cyclosporine A (CsA) is a powerful immunosuppressive drug with side effects including the induction of chronic nephrotoxicity including endoplasmic reticulum (ER) stress in tubular cells. Recently, it was reported that autophagy is induced by ER stress and serves to alleviate the associated deleterious effects. In the current study, CsA treatment (0,100 ,m) decreased cell survival of rat pituitary GH3 cells in a dose-dependent manner. At concentrations ranging from 1.0 to 10 ,m, CsA induced a dose-dependent increase in the expression of microtubule-associated protein 1 light chain 3 (LC3)-I and LC3-II. Cells treated with 2.5 ,m CsA exhibited cytoplasmic vacuolation, indicating that CsA induces autophagy in rat pituitary GH3 cells. In the presence of 1.0,10 ,m CsA, the expression of catalase decreased while that of the ER stress markers, ER luminal binding protein (BiP) and inositol-requiring enzyme 1 alpha (IRE1,), increased as compared those levels in untreated cells. These results suggested that CsA-induced autophagy is dependent on ER stress. To determine whether melatonin would protect cells against CsA-induced autophagy, we treated rat pituitary GH3 cells with melatonin in the presence of CsA. Melatonin treatment (100 and 200 ,m) suppressed autophagy induced by 2.5 and 5 ,m CsA. Furthermore, co-treatment with 100 ,m melatonin inhibited LC3-II expression, and increased catalase and phosphorylated p-ERK levels in the presence of 2.5 and 5 ,m CsA. BiP and IRE1, expression in melatonin-co-treated cells was superior to that in cells treated with 2.5 and 5 ,m CsA alone. Thus, melatonin suppresses CsA-mediated autophagy in rat pituitary GH3 cells. [source]

    Cetirizine in horses: pharmacokinetics and effect of ivermectin pretreatment

    JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2007
    L. OLSÉN
    The pharmacokinetics of the histamine H1 -antagonist cetirizine and the effects of pretreatment with the antiparasitic macrocyclic lactone ivermectin on the pharmacokinetics of cetirizine were studied in horses. After oral administration of cetirizine at 0.2 mg/kg bw, the mean terminal half-life was 3.4 h (range 2.9,3.7 h) and the maximal plasma concentration 132 ng/mL (101,196 ng/mL). The time to reach maximal plasma concentration was 0.7 h (0.5,0.8 h). Ivermectin (0.2 mg/kg bw) given orally 1.5 h before cetirizine did not affect its pharmacokinetics. However, ivermectin pretreatment 12 h before cetirizine increased the area under the plasma concentration,time curve by 60%. The maximal plasma concentration, terminal half-life and mean residence time also increased significantly following the 12 h pretreatment. Ivermectin is an inhibitor of P-glycoprotein, which is a major drug efflux transporter in cellular membranes at various sites. The elevated plasma levels of cetirizine following the pretreatment with ivermectin may mainly be due to decreased renal secretion, related to inhibition of the P-glycoprotein in the proximal tubular cells of the kidney. The pharmacokinetic properties of cetirizine have characteristics which are suitable for an antihistamine, and this substance may be a useful drug in horses. [source]

    Therapeutic implications of the MDR-1 gene

    JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2004
    K. L. Mealey
    Drug transporters significantly influence drug pharmacokinetics and pharmacodynamics. P-glycoprotein (P-gp), the product of the MDR1 (ABCB1) gene, is among the most well-characterized drug transporters, particularly in veterinary medicine. A number of clinically relevant, structurally and functionally unrelated drugs are substrates for P-gp. P-gp is expressed by a variety of normal tissues including the intestines, renal tubular cells, brain capillary endothelial cells, biliary canalicular cells, and others, where it functions to actively extrude substrate drugs. In this capacity, P-gp limits oral absorption and central nervous system entry of many substrate drugs. A number of MDR1 polymorphisms have been described in human patients, some of which result in altered drug pharmacokinetics and susceptibility to diseases such as Parkinson's disease, inflammatory bowel disease, refractory seizures, and others. An MDR1 polymorphism in herding breed dogs, including collies and Australian shepherds, has been demonstrated to be the cause of ivermectin sensitivity in these breeds. Recent evidence suggests that this polymorphism, a 4-bp deletion mutation, results in increased susceptibility to the toxicity of several drugs in addition to ivermectin. Furthermore, data in rodent models suggest that P-gp may play an important role in regulating the hypothalamic,pituitary,adrenal axis. [source]

    Neutrophil gelatinase-associated lipocalin levels in chronic haemodialysis patients

    NEPHROLOGY, Issue 1 2010
    DAVIDE BOLIGNANO
    ABSTRACT: Neutrophil gelatinase-associated lipocalin (NGAL), a small 25 kDa protein strongly induced in injured renal tubular cells, represents an interesting emerging biomarker in the field of clinical nephrology. The aim of the present pilot study was to analyze circulating NGAL levels in a small cohort of 30 patients on chronic haemodialysis (HD), in order to assess any relationships with different laboratory and clinical parameters. Pre- and post-HD levels were higher in patients than in healthy subjects (485.2 ± 49.7 vs 51.2 ± 4.6 ng/mL; P < 0.001; and 167.4 ± 48.0 vs 51.2 ± 4.6 ng/mL; P = 0.01). Furthermore, a single HD session decreased NGAL levels by approximately fourfold (485.2 ± 49.7 vs 167.4 ± 48.0 ng/mL; p:0.01), with a reduction ratio of 73 ± 14%. At baseline, direct and independent correlations were found between NGAL and, respectively, high-sensitivity C-reactive protein (, = 0.34; P = 0.03) and spKt/V (, = 0.35; P = 0.02). The findings showed that HD patients have chronically increased levels of circulating NGAL. However, with a single HD session, a marked reduction was achieved in circulating NGAL values, probably as a result of an important dialytic removal, similar to that observed for other cytokines. Finally, the direct independent correlation found between NGAL and spKt/V raises the question of whether, in the future, NGAL may also become a useful tool in predicting the adequacy of dialysis and in guiding the management of dialysis prescriptions. [source]

    Aldosterone induces collagen synthesis via activation of extracellular signal-regulated kinase 1 and 2 in renal proximal tubules

    NEPHROLOGY, Issue 8 2008
    GUOSHUANG XU
    SUMMARY: Aim: Aldosterone plays a crucial role in renal fibrosis by inducing mesangial cell proliferation and promoting collagen synthesis in renal fibroblasts. However, renal proximal tubule involvement in aldosterone-induced collagen synthesis has not yet been identified. The aim of this study was to examine the potential role of aldosterone in collagen expression and its possible mineralocorticoid receptor (MR)-dependent pathway, mediated by activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) in cultured human renal proximal tubular epithelial (HKC) cells. Methods: After HKC cells were stimulated by aldosterone with different concentrations for various time and periods, the gene expression and protein synthesis of collagen I, II, III and IV were measured by real-time polymerase chain reaction and western blot, respectively. ERK1/2 activation, ,-smooth muscle actin (,-SMA), and E-cadherin were also detected by western blot. Results: Aldosterone can increase ERK1/2 phosphorylation of human renal proximal tubular epithelial cells in a time- and dose-dependent manner. Although aldosterone had no effect on collagen I and II expression, it increased expression of ,-SMA and collagen III and IV and decreased that of E-cadherin in HKC cells after 48 h. These effects could be prevented by a ERK pathway inhibitor, U0126, or by a selective MR antagonist, spironolactone. Conclusion: The results suggest that aldosterone plays a pivotal role in tubulointerstitial fibrosis by promoting tubular epithelial,mesenchymal transition and collagen synthesis in proximal tubular cells. The process is MR-dependent, and mediated by ERK1/2 mitogen-activated protein kinase pathway. [source]

    Extracellular signal-regulated kinase-dependent interstitial macrophage proliferation in the obstructed mouse kidney

    NEPHROLOGY, Issue 5 2008
    YINGJIE HAN
    SUMMARY: Aim: A number of growth factors have been shown to induce proliferation of renal cell types in animal models of kidney disease. In vitro studies suggest that many such growth factors induce renal cell proliferation through the extracellular signal-regulated kinase (ERK) pathway. The aim of this study was to determine the functional role of ERK signalling in cell proliferation in the obstructed kidney. Methods: Unilateral ureteric obstruction was induced in C57BL/6J mice which then received an ERK inhibitor drug (U0126 100 mg/kg t.i.d.), vehicle (DMSO) or no treatment, starting at day 2 after unilateral ureteric obstruction surgery and continuing until animals were killed on day 5. Cell proliferation was assessed by uptake of bromodeoxyuridine (BrdU). Results: In normal mice, phosphorylation (activation) of ERK (p-ERK) was restricted to collecting ducts. Western blotting identified a marked increase in p-ERK in the obstructed kidney in the no-treatment and vehicle-treated groups. Immunostaining showed strong p-ERK staining in many tubules and in interstitial cells. U0126 treatment inhibited ERK phosphorylation as assessed by western blot and immunostaining. The number of BrdU+ cortical tubular cells was reduced by vehicle treatment but was not further changed by U0126 treatment. In contrast, interstitial cell proliferation in the obstructed kidney was unaltered by vehicle treatment, but this was significantly inhibited by U0126. This was associated with a reduction in interstitial macrophage accumulation, but no effect was seen upon interstitial accumulation of ,-SMA+ myofibroblasts. Renal fibrosis, as assessed by collagen deposition, was unaffected by U0126 or vehicle treatment. Conclusion: These studies show that accumulation of interstitial macrophages in the obstructed kidney is, in part, dependent upon the ERK signalling pathway. [source]

    The differential regulation of Smad7 in kidney tubule cells by connective tissue growth factor and transforming growth factor-beta1

    NEPHROLOGY, Issue 3 2007
    WEIER QI
    Summary: Aims: Smad7 is an inhibitory Smad that regulates transforming growth factor-, (TGF-,) signaling. Connective tissue growth factor (CTGF) is recognized as a potent downstream mediator of the fibrogenic effects of TGF-,1. SMAD binding sites have been identified in both TGF-, and CTGF promoters. The effect of CTGF on Smad7 expression and its role in the regulation of Smad7 induced by TGF-,1 in renal tubular cells is unknown. Methods: Human model of proximal tubular cells (HK-2 cells) was used and confirmed using a diabetic rat model. RT-PCR was performed to measure Smad7, TGF-,1 and Smad2 and ELISA was performed to measure active TGF-,1. CTGF or TGF-,1 was silenced in HK-2 cells using siRNA methodology. Results: TGF-,1 induced Smad7 in a time-dependent manner, peaking at 30 min (P < 0.0005) but sustained up to 24 hrs (p < 0.005). Conversely, CTGF reduced Smad7, which was maximal at 24 hrs (p < 0.05). This was supported by our in vivo data demonstrating that CTGF protein significantly increased while Smad7 mRNA level was reduced in a diabetic rat model. The basal expression level of Smad7 decreased in TGF-,1 silenced cells compared to cells transfected with non-specific siRNA (p < 0.0005). The basal expression level of Smad7 increased in CTGF silenced cells (p < 0.05), which was increased by TGF-,1 (p < 0.005). Both mRNA and protein levels of TGF-,1 decreased in CTGF silenced cells (p < 0.05 and p < 0.005 respectively) accompanied by reduction in Smad2 mRNA level in CTGF silenced cells. Conclusions: Smad7 is induced rapidly by TGF-,1 limiting the response to TGF-,1. CTGF likely plays a key role in promoting TGF-,1 activity by decreasing the availability of Smad7 and increasing Smad2. [source]

    Apoptosis of circulating lymphocyte in rats with unilateral ureteral obstruction: Role of angiotensin II

    NEPHROLOGY, Issue 5 2005
    SOMCHIT EIAM-ONG
    SUMMARY: Background: Unilateral ureteral obstruction (UUO) could induce increased renal angiotensin II (ANG II), which enhances apoptosis of renal tubular cells and renal tissue loss. Systemic ANG II is also increased in UUO. There are no data available about whether UUO can induce apoptosis of circulating lymphocytes or not. Methods: UUO or sham-operated male Wistar rats (n = 8 in each group) were fed a drinking solution containing water, angiotensin II receptor type 1 antagonist (ARA; losartan, 500 mg/L) or angiotensin-converting enzyme inhibitor (ACEI; enalapril: 200 mg/L) for 1 day or 7 days. Blood samples were collected and circulating lymphocyte cells were separated. The apoptotic cells were detected by in situ terminal deoxynucleotidyl transferase (TdT assay)-mediated digoxigenin/antidigoxigenin conjugated fluorescein method and counted under a fluorescence microscope. The apoptotic index was calculated. Results: UUO caused marked increases in the apoptotic index of circulating lymphocytes in UUO rats at both 1 day and 7 days when compared with the respective sham groups (P < 0.001). Neither ARA nor ACEI treatment had an effect on the apoptotic index values in the UUO rats at 1 day. In the UUO rats at 7 days, the apoptosis of circulating lymphocytes was markedly decreased from 29.2 ± 2.7% to 11.9 ± 2.7% (P < 0.01) in the ARA-treated rats and to 7.6 ± 2.7% (P < 0.001) in the ACEI-treated rats. Conclusion: UUO, via stimulation of ANG II, could promptly enhance apoptosis of circulating lymphocytes. The apoptosis persisted throughout the 7 days of the study. Prolonged UUO would impair lymphocyte cell immunity and the host defense mechanism. Continuous treatment with either ARA or ACEI could abrogate ANG II-stimulated circulating lymphocyte apoptosis. [source]