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Aristolochic Acid (aristolochic + acid)
Selected AbstractsSELDI-TOF as a method for biomarker discovery in the urine of aristolochic-acid-treated miceELECTROPHORESIS, Issue 7 2009Feilei Huang Abstract Aristolochic acids (AAs) present in Aristolochia plants are substances responsible for Chinese herbs nephropathy. Recently, strong indications have also been presented, which dietary poisoning with AA is responsible for endemic (Balkan) nephropathy (EN), an enigmatic renal disease that affects rural population living in some countries in Southeastern Europe. A mouse model was applied to follow the effects of two forms of AA, AAI and AAII. SDS-PAGE and SELDI-TOF mass spectrometry with normal phase chips were used to evaluate changes in the urine of treated animals. These two methods are demonstrated to be comparable. The use of SELDI-TOF MS for rapid analysis of a large number of samples and the combination of this method with nano-LC-ESI MS/MS for protein identification were demonstrated. Biomarker discovery after analysis of large cohort of EN patients will be the final aim of these investigations. [source] Fanconi's syndrome and subsequent progressive renal failure caused by a Chinese herb containing aristolochic acidNEPHROLOGY, Issue 3 2004SANGHO LEE SUMMARY: Chinese herb nephropathy contains a variety of clinical features of progressive renal failure (indicated by studies conducted in Belgium) to the variant type of Fanconi's syndrome. Fanconi's syndrome has mostly been reported in Asian countries, and is characterized by proximal tubular dysfunction and slower progression to end-stage renal disease (ESRD); it also often revealed a reversible clinical course. We describe a 43-year-old woman who presented with polyuria and polydipsia caused by Fanconi's syndrome. The cause of Fanconi's syndrome was not identified because the patient denied the intake of the Chinese herbal mixture at first. Fanconi's syndrome seemed to be reversible in its early stage, but it rapidly progressed to renal failure after 3 months, despite the interruption of Chinese mixture use. A renal biopsy revealed typical findings of aristolochic acid-induced nephropathy. Aristolochic acids were also detected in the Chinese herbs that were consumed. This case highlights the variety of the clinical spectrum of aristolochic acid induced nephropathy (AAN). We emphasize that AAN should be suspected in all patients with Fanconi's syndrome, even if patients deny the intake of any Chinese herbal preparation. [source] Econazole-induced Ca2+ fluxes and apoptosis in human oral cancer cellsDRUG DEVELOPMENT RESEARCH, Issue 4 2010Daih-Huang Kuo Abstract The effect of econazole on cytosolic free Ca2+ concentrations ([Ca2+]i) and viability was explored in human oral cancer cells (OC2), using the fluorescent dyes fura-2 and WST-1, respectively. Econazole at concentrations of >1,µM increased [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced partly by removing extracellular Ca2+. The econazole-induced Ca2+ influx was sensitive to blockade of aristolochic acid (phospholipase A2 inhibitor) and GF109203X (PKC inhibitor). In Ca2+ -free medium, after treatment with 1,µM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor), 30,µM econazole failed to induce a [Ca2+]i rise. Inhibition of phospholipase C with 2,µM U73122 substantially suppressed econazole-induced [Ca2+]i rise. At concentrations of 5,70,µM econazole killed cells in a concentration-dependent manner. The cytotoxic effect of 50,µM econazole was enhanced by prechelating cytosolic Ca2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N,,N,-tetraacetic acid (BAPTA). The ERK MAPK inhibitor, PD98059 (10,µM), also enhanced 20,µM econazole-induced cell death. Propidium iodide staining data suggest that econazole induced apoptosis between concentrations of 10,70,µM. Collectively, in OC2 cells, econazole induced [Ca2+]i rises by causing Ca2+ release from the endoplasmic reticulum and Ca2+ influx from phospholipase A2/PKC-regulated Ca2+ channels. Furthermore, econazole caused cell death appeared to be regulated by ERK MAPK. Drug Dev Res 71: 240,248, 2010. © 2010 Wiley-Liss, Inc. [source] Effect of capsaicin on Ca2+ fluxes in Madin-Darby canine renal tubular cellsDRUG DEVELOPMENT RESEARCH, Issue 2 2010Jeng-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] TP53 mutation signature supports involvement of aristolochic acid in the aetiology of endemic nephropathy-associated tumoursINTERNATIONAL JOURNAL OF CANCER, Issue 4 2009Tatiana Nedelko Abstract The proposal has been put forward that the primary cause of Balkan endemic nephropathy (BEN) is exposure to food crops contaminated with seeds of Aristolochia spp, which contain high levels of aristolochic acids (AA). Recently, tumour DNA samples from patients with BEN were found to harbour principally A to T mutations in the TP53 tumour suppressor gene (Grollman et al., Proc Natl Acad Sci USA 2007;104:12129,34). Using a novel mutation assay in which we can induce and select mutations in human TP53 sequences in vitro by exposure of cultured cells to a mutagen, we found that A to T mutations were elicited by aristolochic acid at sites in TP53 rarely mutated in human cancers in general, but which were observed in the BEN patients. This concordance of specific mutations in patient tumours and aristolochic acid I-exposed cultures supports the argument that AA has a direct role in the aetiology of BEN-associated cancer. © 2008 Wiley-Liss, Inc. [source] Fanconi's syndrome and subsequent progressive renal failure caused by a Chinese herb containing aristolochic acidNEPHROLOGY, Issue 3 2004SANGHO LEE SUMMARY: Chinese herb nephropathy contains a variety of clinical features of progressive renal failure (indicated by studies conducted in Belgium) to the variant type of Fanconi's syndrome. Fanconi's syndrome has mostly been reported in Asian countries, and is characterized by proximal tubular dysfunction and slower progression to end-stage renal disease (ESRD); it also often revealed a reversible clinical course. We describe a 43-year-old woman who presented with polyuria and polydipsia caused by Fanconi's syndrome. The cause of Fanconi's syndrome was not identified because the patient denied the intake of the Chinese herbal mixture at first. Fanconi's syndrome seemed to be reversible in its early stage, but it rapidly progressed to renal failure after 3 months, despite the interruption of Chinese mixture use. A renal biopsy revealed typical findings of aristolochic acid-induced nephropathy. Aristolochic acids were also detected in the Chinese herbs that were consumed. This case highlights the variety of the clinical spectrum of aristolochic acid induced nephropathy (AAN). We emphasize that AAN should be suspected in all patients with Fanconi's syndrome, even if patients deny the intake of any Chinese herbal preparation. [source] Citrus abscission and Arabidopsis plant decline in response to 5-chloro-3-methyl-4-nitro-1H -pyrazole are mediated by lipid signallingPLANT CELL & ENVIRONMENT, Issue 11 2005FERNANDO ALFEREZ ABSTRACT The compound 5-chloro-3-methyl-4-nitro-1H -pyrazole (CMNP) is a pyrazole-derivative that induces abscission selectively in mature citrus (Citrus sinensis) fruit when applied to the canopy and has herbicidal activity on plants when applied to roots. Despite the favourable efficacy of this compound, the mode of action remains unknown. To gain information about the mode of action of CMNP, the effect of application to mature citrus fruit and Arabidopsis thaliana roots was explored. Peel contact was essential for mature fruit abscission in citrus, whereas root drenching was essential for symptom development and plant decline in Arabidopsis. CMNP was identified as an uncoupler in isolated soybean (Glycine max) mitochondria and pea (Pisum sativum) chloroplasts and an inhibitor of alcohol dehydrogenase in citrus peel, but not an inhibitor of protoporphyrinogen IX oxidase. CMNP treatment reduced ATP content in citrus peel and Arabidopsis leaves. Phospholipase A2 (PLA2) and lipoxygenase (LOX) activities, and lipid hydroperoxide (LPO) levels increased in flavedo of citrus fruit peel and leaves of Arabidopsis plants treated with CMNP. An inhibitor of PLA2 activity, aristolochic acid (AT), reduced CMNP-induced increases in PLA2 and LOX activities and LPO levels in citrus flavedo and Arabidopsis leaves and greatly reduced abscission in citrus and delayed symptoms of plant decline in Arabidopsis. However, AT treatment failed to halt the reduction in ATP content. Reduction in ATP content preceded the increase in PLA2 and LOX activities, LPO content and the biological response. The results indicate a link between lipid signalling, abscission in citrus and herbicidal damage in Arabidopsis. [source] Liquid chromatography/mass spectrometry for metabonomics investigation of the biochemical effects induced by aristolochic acid in rats: the use of information-dependent acquisition for biomarker identificationRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 6 2008Wan Chan The toxic effects of oral administrations of nephrotoxic and carcinogenic aristolochic acid (AA) to male Sprague-Dawley rats were investigated by using high-performance liquid chromatography coupled with a quadrupole time-of-flight mass spectrometer. Analysis of the urine and plasma samples revealed distinct changes in the biochemical patterns in the AA-dosed rats. After peak finding and alignment, principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) were used for multivariate data analysis. Potential biomarkers were studied by high-resolution mass spectrometry (MS) and tandem mass spectrometry (MS/MS) analyses. The MS/MS spectra of all endogenous metabolites satisfying the pre-defined criteria were acquired in a single information-dependent acquisition (IDA) analysis, demonstrating that IDA was an efficient approach for structural elucidation in metabonomic studies. Citric acid and a glucuronide-containing metabolite were observed as potential biomarkers in rat urine. A significant increase in plasma creatinine concentration was also observed in the AA-dosed rats, which indicated that AA induced an adverse effect on the renal clearance function. Copyright © 2008 John Wiley & Sons, Ltd. [source] Lindane (,-Hexachlorocyclohexane) Induces Internal Ca2+ Release and Capacitative Ca2+ Entry in Madin-Darby Canine Kidney CellsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2000Cheng-Hsien Lu The effect of lindane (,-hexachlorocyclohexane), an organochlorine pesticide, on Ca2+ mobilization in Madin-Darby canine kidney cells was examined by fluorimetry using fura-2 as a Ca2+ indicator. Lindane (5,200 ,M) increased [Ca2+]i concentration-dependently. The [Ca2+]i signal comprised an immediate initial rise followed by a persistent phase. Ca2+ removal inhibited the [Ca2+]i signal by reducing both the initial rise and the sustained phase. This implies lindane-triggered Ca2+ influx and Ca2+ release. In Ca2+ -free medium, 0.15 mM lindane increased [Ca2+]i after pretreatment with carbonylcyanide m-chlorophenylhydrazone (CCCP; 2 ,M), a mitochondrial uncoupler, and two endoplasmic reticulum Ca2+ pump inhibitors, thapsigargin and cyclopiazonic acid. Conversely, pretreatment with lindane abolished CCCP- and thapsigargin-induced Ca2+ release. This suggests that 0.15 mM lindane released Ca2+ from the endoplasmic reticulum, mitochondria and other stores. La3+ (1 mM) partly inhibited 0.1 mM lindane-induced [Ca2+]i increase, confirming that lindane induced Ca2+ influx. Addition of 3 mM Ca2+ increased [Ca2+]i after pretreatment with 0.15 mM lindane for 750 sec. in Ca2+ -free medium, which indicates lindane-induced capacitative Ca2+ entry. Lindane (0.15 mM)-induced Ca2+ release was not reduced by inhibiting phospholipase C with 2 ,M U73122, but was inhibited by 70% by the phospholipase A2 inhibitor aristolochic acid (40 ,M). [source] Analysis of aristolochic acids by CE-MS with carboxymethyl chitosan-coated capillaryELECTROPHORESIS, Issue 10 2009Xiaofang Fu Abstract A CE-MS method for rapid determination of aristolochic acid-I and aristolochic acid-II (AA-II) in traditional Chinese medicines and biological samples was described in the present paper. AA-I and AA-II can be baseline separated within 6,min by CE-MS with carboxymethyl-chitosan-coated capillary. CZE conditions including pH, concentration of buffer, applied voltage, and capillary temperature were systematically investigated, and the composition and flow rate of sheath liquid were also optimized for CE-MS. Furthermore, the CE-UV method without any additives in BGE solution was established and compared with the CE-MS method. The results showed that the two methods could achieve satisfactory separation efficiency, repeatability, and linearity, while the LOD was 0.6,,g/mL for CE-UV and 0.05,,g/mL for CE-MS. Compared with the CE-UV method, the sensitivity of CE-MS was significantly improved, in addition to the structure information provided by MS detection at the same time. As an application example, a spiked sample in human serum was analyzed by the CE-MS method, indicating that the new CE-MS method can be applied to analyze AAs in biological samples. [source] TP53 mutation signature supports involvement of aristolochic acid in the aetiology of endemic nephropathy-associated tumoursINTERNATIONAL JOURNAL OF CANCER, Issue 4 2009Tatiana Nedelko Abstract The proposal has been put forward that the primary cause of Balkan endemic nephropathy (BEN) is exposure to food crops contaminated with seeds of Aristolochia spp, which contain high levels of aristolochic acids (AA). Recently, tumour DNA samples from patients with BEN were found to harbour principally A to T mutations in the TP53 tumour suppressor gene (Grollman et al., Proc Natl Acad Sci USA 2007;104:12129,34). Using a novel mutation assay in which we can induce and select mutations in human TP53 sequences in vitro by exposure of cultured cells to a mutagen, we found that A to T mutations were elicited by aristolochic acid at sites in TP53 rarely mutated in human cancers in general, but which were observed in the BEN patients. This concordance of specific mutations in patient tumours and aristolochic acid I-exposed cultures supports the argument that AA has a direct role in the aetiology of BEN-associated cancer. © 2008 Wiley-Liss, Inc. [source] Simultaneous determination of five aristolochic acids and two aristololactams in Aristolochia plants by high-performance liquid chromatographyBIOMEDICAL CHROMATOGRAPHY, Issue 4 2006Cuiying Zhang Abstract An HPLC method was developed for the simultaneous determination of five aristolochic acids (AAs) and two aristololactams (ALs) in the following six Chinese drugs derived from Aristolochia species. Samples were analyzed on a C18 column with acetonitrile and 3.7 mm phosphoric acid buffer gradient elution, detected at 260 nm. Assay was linear over the range (µg/mL) 0.386,38.6 for aristolochic acid Va, 0.632,63.2 for aristolochic acid IVa, 0.200,20.0 for 9-hydroxy aristolochic acid I, 0.352,35.2 for aristololactam II, 0.296,29.6 for aristolochic acid II, 0.274,27.4 for aristololactam I and 3.12,312 for aristolochic acid I. Average recoveries (%) of samples were 102.0, 95.9, 99.2, 102.2, 97.2, 97.1 and 97.8 for these seven constituents, respectively. The detection limit and retention time for the seven constituents ranged from 10.0 to 15.8 ng/mL and from 12 to 21 min. As a result of drug determination, contents (in mg/g) were as follows: AA-I, 0.69,1.77; AA-II, 0.02,0.18; 9-OH AA-I, 0.04,0.12; AA-IVa, 0.76,3.36; AA-Va, 0.04,0.31; AL-I, 0.07,0.36; and AL-II, 0.01,0.09 in Madouling; AA-I, 0.03,0.41; AA-II, 0.01,0.11; 9-OH AA-I, 0.00,0.60; AA-IVa, 0.00,0.77; AA-Va, 0.00,0.14; and AL-I, 0.00,0.04 in Tianxianteng; AA-I, 1.19,4.71; and AA-II, 0.24,1.69 in Qingmuxiang; AA-I, 2.79,5.48; AA-II, 1.06,1.86; 9-OH AA-I, 0.01,0.09; AA-IVa, 0.38,0.69; AA-Va, 0.00,0.61; AL-I, 0.00,0.02; and AL-II, 0.00,0.02 in Bei-madouling-gen; AA-I, 0.64,4.23; AA-II, 0.06,0.40; and AA-IVa, 0.08,0.25; in Guangfangji; and AA-I, 1.88,9.72; AA-II, 0.26,1.88; and AA-IVa, 0.09,0.52 in Guanmutong. The other constituents were not detected in Tianxianteng, Qingmuxiang, Guangfangji and Guanmutong. Copyright © 2005 John Wiley & Sons, Ltd. [source] | ||||||||||||||||