Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Aristolochic Acids”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1975

Fluorometric and GLC analyses of aristolochic acid.

Aristolochic acid is a natural product with possible implication in Balkan endemic nephropathy. A convenient fluorometric assay for the compound is described based on reduction to the lactam and measurement of the intensity of fluorescence. The limit of sensitivity was 0.05 mug/ml. A GLC assay is also described, based on flash methylation of aristolochic acid and its lactam using trimethylanilinium hydroxide. Conditions for optimum performance with a sensitivity limit of 1-5 mug/ml are described.

Aniline Compounds↗
PubMed1993

Induction of hepatic nodules in the rat by aristolochic acid.

Aristolochic acid (AA), used as an anti-inflammatory agent in the past, is known to be mutagenic and carcinogenic to several organs of the rat, including forestomach, renal pelvis and urinary bladder. However, despite the induction of DNA adducts in the liver, no carcinogenic potential of AA has been reported in the latter organ. The present study was based on the rationale that the lack of carcinogenicity of AA to the liver could be because this chemical may not be necrogenic at the doses examined and liver cell proliferation has been established as an essential component for initiation of liver carcinogenesis in the rat. The results indicated that AA is non-necrogenic to the rat liver. However, a single non-necrogenic dose of AA (10 mg/kg b.w., i.p.) given 18 hours after 2/3 partial hepatectomy initiated liver cell carcinogenesis. The initiated cells are promotable with 1% dietary orotic acid, a liver tumor promoter, to form glutathione-S-transferase 7-7 positive hepatic foci and nodules.

Animals↗
PubMed2006

[Advances in studies on pharmacokinetics of aristolochic acid I].

Aristolochic acid I (AA-I) was absorbed and distributed quickly in vivo, the plasma concentration-time curve were fit with the open two-compartment model and one-compartment model, respectively. The elimination of AA-I has relationship with the dosage, the low dose group eliminates more quickly than the high dose group. The characters of pharmacokinetics of AA-I induce the cumulation of AA-I in vivo and the nephrotoxin to the kidney and other viscera.

Administration, Oral↗
PubMed2004

Application of simplified in vitro screening tests to detect genotoxicity of aristolochic acid.

Aristolochic acid (AA), the active compound found in Aristolochia extracts, has been used as a traditional medicine. However, products containing AA were withdrawn from the market in the early 1980s because AA was found to be a potent carcinogen. Some genotoxicity studies of AA were conducted after the carcinogenicity of AA was reported. The purpose of this study was to check the ability of simplified, screening tests for genotoxicity to indicate the genotoxic activities of AA. Four commonly used in vitro genotoxicity endpoints were examined. In a bacterial mutation screening test, AA was mutagenic to tester strains TA98 and TA100 with and without rat liver S9. In the L5178Y mouse lymphoma cell gene mutation test, mutagenic activity was observed at > or = 25 microg/ml with or without S9. A concentration-dependent increase in structural chromosome aberrations was observed in CHO cells, with significant increases at 50 microg/ml without S9 and at 25 microg/ml with S9. Significant increases in micronucleated binucleated cells were observed in CHO cells treated with AA at > or = 25 microg/ml with or without S9. These results demonstrated that the genotoxicity of AA would have been easily detected if simple screening versions of in vitro genotoxicity assays had been used during early product development. It is suggested that simplified screening tests such as those used in this study would be a rapid and economical way of obtaining the preliminary genotoxicity profiles of new substances or products as an aid to decision-making for further development.

Animals↗
PubMed2005

Mast cell infiltration associated with tubulointerstitial fibrosis in chronic Aristolochic Acid Nephropathy.

Aristolochic Acid Nephropathy (AAN) is regarded as a kind of toxic nephropathy caused by the formation of DNA- aristolochic acid adducts in renal parenchymal cells. However, the underlying mechanisms driving the progression of renal interstitial fibrosis in AAN still remains unclear. This study aims to elucidate the role of some immunological factors, especially mast cells (MCs), in the pathogenesis of AAN. Sixteen patients with AAN were enrolled in this study, including five acute and 11 chronic AAN. Monoclonal antibodies against human tryptase, alpha smooth muscle actin (alpha-SMA), and CD68 were applied on serial sections, which were further counterstained with Periodic Acid-Schiff. It was found that massive tryptase-positive MCs were observed in the fibrotic areas in chronic AAN, especially around thickened tubular basement membranes where myofibroblasts accumulated too. In contrast, MCs infiltrated to a less extent in acute AAN, and were barely found in normal control kidneys. In chronic AAN, the number of MCs in the tubulointerstitium was positively correlated with the degree of renal fibrosis (r=0.64, P <0.05), but not with serum creatinine levels. Meanwhile, the recruitment of MCs into the renal interstitium is accompanied with local proliferation of myofibroblasts. Macrophages were not abundant, neither in acute nor in chronic AAN. Our findings show for the first time that mast cell infiltration seems to be associated with the progression of fibrosis in the renal tubulointerstitium in chronic AAN.

Acute Disease↗
PubMed1981

[Antagonistic effects of glucocorticoids and aristolochic acid on the immunocyte adherence phenomenon (author's transl)].

The influence of prednisolone and 3,4-methylenedioxy-8-methoxy-10-nitrophenanthrenecarbonic acid-1 (aristolochic acid) on the immunocyte adherence phenomenon in the rat was investigated. The following results were obtained: Prednisolone diminishes the number of rosettes. Aristolochic acid itself has no influence on the number of rosettes but compensates the diminuation caused by prednisolone. Equal effects were found for 5 mg/kg b.w. prednisolone and 0.005 mg/kg aristolochic acid. This effect of aristolochic acid is interpreted as competitive inhibition of surface receptors of lymphocytes.

Animals↗
PubMed2006

A sensitive enzyme-linked immunosorbent assay for detecting carcinogenic aristolochic acid in herbal remedies.

Aristolochic acid, a naturally occurring nephrotoxin and rodent carcinogen, has been associated with the development of various nephropathies in humans. Developing a sensitive and rapid method to screen the aristolochic acid levels in herbal remedies is urgent for protecting public health. Polyclonal antibodies for aristolochic acid were generated from rabbits after the animals had been immunized with either aristolochic acid-ovalbumin (OVA) or aristolochic acid-keyhole limpet hemocyanin (KLH). A competitive indirect enzyme-linked immunosorbent assay (ciELISA) and a competitive direct enzyme-linked immunosorbent assay (cdELISA) were used for the characterization of the antibodies and for analysis of aristolochic acid contaminated in herbal medicine and diet pills. The antibody titers in the serum of rabbits immunized with aristolochic acid-OVA were considerably higher than those from aristolochic acid-KLH-immunized rabbits. The antibodies from the aristolochic acid-OVA-immunized rabbits were further characterized. In the ciELISA with aristolochic acid-KLH as the plate-coating antigen, the concentrations of the aristolochic acid mixture, aristolochic acid I, and aristolochic acid II that caused 50% inhibition (IC50) of binding of antibodies to aristolochic acid-KLH were found to be 1.2, 0.7, and 18 ng/mL, respectively. When 0.25-5 microg/g of standard aristolochic acid was spiked to ground lotus seeds and then extracted with 0.01 M phosphate-buffered saline, the recovery rate was found to be 86.5% in the ciELISA. Analysis of aristolochic acid in herbal medicine and diet pills with ciELISA showed that 10 of the 12 examined samples were contaminated at levels from 0.6 to 655 microg/g. The presence of aristolochic acid was also confirmed by the high-performance liquid chromatography method.

Animals↗
PubMed2004

The renin-angiotensin system blockade does not prevent renal interstitial fibrosis induced by aristolochic acids.

BACKGROUND: Experimental aristolochic acid nephropathy (AAN), characterized by interstitial fibrosis, tubular atrophy, and chronic renal failure, was reported after 35-day injections of aristolochic acids (AA) to salt-depleted male Wistar rats. The link between renal fibrosis and the renin-angiotensin system (RAS) in this model remains unknown. METHODS: We investigated the impact of sodium diets (low and normal), of RAS inhibition with enalapril (ENA) alone, or combined with candesartan (CSN) for 35 days, and ENA + CSN for 65 days on AAN development. At the end of each observation period, blood pressure and renal angiotensin-converting enzyme activity were measured, as well as renal functional impairment (plasma creatinine increase, proteinuria) and histologic lesions (interstitial fibrosis, monocytes/macrophages infiltration, myofibroblasts collagens type I and IV, proliferating cells). RESULTS: Sodium intake did not modify renal functional and morphologic impairment induced by AA. The RAS blockade by ENA or ENA + CSN in rats receiving AA did not result in any statistical difference in terms of renal failure, proteinuria, and interstitial fibrosis on day 35 or 65. On day 35, the monocytes/macrophages infiltration was significantly decreased by two-fold when ENA (P < 0.01) or ENA + CSN (P < 0.01) was given from day 0. CONCLUSION: Our data demonstrate that RAS modulation by salt depletion and pharmacologic blockade do not influence renal failure and interstitial fibrosis in the rat model of AAN. We suggest that pathways of interstitial renal fibrosis may be independent of RAS at least in some conditions.

Angiotensin II Type 1 Receptor Blockers↗
PubMed1998

[Aristolochic acids in herbal medicines].

Aristolochic acids are nitrophenanthrenes with a carboxylic acid fanction which have been found only among the Aristolochiaceae. In 1993, rapidly progressive interstitial renal fibrosis has been reported in women have been on a slimming regimen including Chinese herbal medicines in Belgium. In Japan, at the Kansai district, several cases of Chinese herbs nephropathy have been reported quite recently. In both cases, aristolochic acids was detected in the Chinese herbal medicines taken by the patients. We have Asiasarum Root, a species of Aristolochiaceae, in Japanese Pharmacopoeia. Therefore, we quantitatively analysed aristolochic acids in these herbal medicines and related plants.

Antineoplastic Agents↗
PubMed2004

Acute nephrotoxicity of aristolochic acids in mice.

Aristolochic acids (AA), present in Aristolochia plants, are the toxin responsible for Chinese herbs nephropathy (CHN), a rapidly progressive tubulointerstitial nephritis (TIN). To clarify the mechanisms of the development of CHN, we tried to induce TIN in mice using AA. Three strains of inbred mice, BALB/c, C3H/He and C57BL/6, received 2.5 mg kg(-1) of AA or AA sodium salt (AANa) daily by intraperitoneal or oral administration, 5 days a week for 2 weeks. Serum and renal tissue were obtained at sacrifice. Twelve-hour urine samples were individually collected in a metabolic cage at one-week intervals. In the AA-injected groups, severe tubular injury, with the appearance of acute tubular necrosis, and rare cell infiltration into the interstitium, were seen in BALB/c mice. C3H/He mice also developed TIN with prominent cell infiltration into the interstitium and interstitial fibrosis. In C57BL/6 mice, only mild and focal tubulointerstitial changes were seen. Serum creatinine and blood urea nitrogen increased in BALB/c and C3H/He mice. Immunofluorescent study revealed no deposition of immune components in kidneys. In the AANa-treated groups, TIN was also seen in all groups, but even more severe tubulointerstitial changes were induced by intraperitoneal injection. Further examination using purified AAI, AAII, AAIVa and aristolactam I (ALI) revealed that AAI induced strong nephrotoxicity in mice, and that AAII resulted in mild nephrotoxicity. However, AAIVa and ALI caused no nephrotoxicity in this experimental system. There are strain differences in mice in their susceptibility to AA nephropathy. AAI exerted the strongest nephrotoxic effect in mice.

Acute Disease↗
PubMed1992

Detection and quantitation of dG-AAI and dA-AAI adducts by 32P-postlabeling methods in urothelium and exfoliated cells in urine of rats treated with aristolochic acid I.

Analysis of aristolochic acid I (AAI)-DNA adducts in exfoliated cells in urine, urothelium and entire urinary bladder were studied after oral administration of five daily doses (10 mg/kg body wt) AAI for 3 months to rats. The two major adducts excreted in urine are presumably identical to the two main adducts formed in vitro and in vivo in different organs in the rat, which have previously been characterized in vitro as 7(-deoxyguanosin-N2-yl)-aristolactam I and 7(-deoxyadenosin-N6-yl)-aristolactam I. Urine samples were collected on dry-ice, subsequently pooled and purified according to the protocol of Kadlubar and co-workers. DNA was isolated, digested and AAI-DNA adducts of exfoliated cells in urine and urothelium of rats were detected and quantitated by enhancement methods of the 32P-postlabeling assay, namely nuclease P1 enrichment or butanol extraction. Autoradiograms indicated that adduct patterns in DNA derived from exfoliated cells in urine were very similar to those obtained from DNA isolated from tissues. Quantitative analysis of adducts revealed adduct levels declining for both adducts from DNA isolated from urothelium to DNA isolated from the entire urinary bladder to DNA isolated from exfoliated cells in urine. In general, count rates of two predominant AAI adducts were enhanced by butanol extraction approximately 3- to 8-fold when compared with the nuclease P1 digestion technique. The identity of the two major adducts was confirmed by co-chromatography with eluted spots from in vivo adducts by comparing mobilities on poly-(ethyleneimine)-cellulose plates. Microbiological investigations of the urine revealed no gross contamination with bacteria, so that the isolated DNA supposedly originated from exfoliated urothelial cells. This study indicates that 32P-postlabeling analysis can be used to monitor non-invasively the formation of carcinogen-DNA adducts in animals or humans exposed to carcinogens.

Adenosine↗
PubMed1991

Activating mutations at codon 61 of the c-Ha-ras gene in thin-tissue sections of tumors induced by aristolochic acid in rats and mice.

The plant extract aristolochic acid, which consists mainly of aristolochic acid I (AAI) and aristolochic acid II (AAII), induces tumors in rats and mice. Thin-tissue sections of rat tumors induced by AAI and of mouse tumors induced by aristolochic acid, were analyzed for c-Ha-ras mutations in codon 61. Areas of neoplastic and histologically normal tissue were manually scraped out and separated. Using the polymerase chain reaction (PCR) and mutation detection by selective oligonucleotide hybridization, we observed AT----TA transversion mutations in DNA of neoplastic portions, but not in DNA of adjacent normal tissue in both rat and mouse tumors.

Animals↗
PubMed1989

Effects of aristolochic acid on phospholipase A2 activity and arachidonate metabolism of human neutrophils.

Aristolochic acid is an alkaloid which has recently been shown to have anti-inflammatory activity against edema in mouse foot pads induced by phospholipases A2 from human synovial fluid. The present study has investigated the effects of aristolochic acid on phospholipase activity and arachidonic acid mobilization in human neutrophils. We find that aristolochic acid is a dose-dependent inhibitor of the calcium-dependent neutral active phospholipase A2 isolated from human neutrophils. As much as 90% of the A23187-stimulated release of previously incorporated [3H]arachidonate from intact neutrophils is inhibited by aristolochic acid; the effect is dose-dependent, with an IC50 of 40 microM, and quite rapid, with near maximal inhibition within 5 min. Aristolochic acid inhibits the A23187-stimulated loss of [3H]arachidonate from both choline- and inositol-phospholipids. Decreased release of free [3H]arachidonate is accompanied by a concomitant decrease in synthesis of [3H]leukotriene B4 and [3H]hydroxyeicosatetraenoic acids. Furthermore, aristolochic acid also inhibits the A23187-stimulated synthesis of [3H]alkylacetylglycerophosphocholine from cellular [3H]alkylacylglycerophosphocholine. These results indicate that aristolochic acid is an effective inhibitor of the A23187-stimulated phospholipase A2 activity in human neutrophils.

Arachidonic Acid↗
PubMed1987

Interaction of phospholipase A2 from Vipera russelli venom with aristolochic acid: a circular dichroism study.

The interaction of aristolochic acid, an alkaloid from Aristolochia species, with phospholipase A2 (PLA2) from Vipera russelli venom was followed by circular dichroism measurements. Aristolochic acid is a non-competitive inhibitor of PLA2. The binding of aristolochic acid to PLA2 induces an extrinsic CD band at 320 nm. The association constant was determined by following the intensity of the extrinsic CD band. Aristolochic acid forms a 1:1 complex with PLA2, with an association constant K, of 5.4 X 10(3) M-1 and a Gibb's free energy change (delta G0) for the reaction of -5.1 kcal/mole. The values of association constant and delta G0 suggest that the interaction is weak. Binding of aristolochic acid causes a change in the secondary structure of the protein which is characterized by an increase in the apparent content of alpha-helix, without any detectable change in the tertiary structure of PLA2.

Aristolochic Acids↗
PubMed2006

[Research on the interaction of aristolochic acid and bovine serum albumin].

The interaction between aristolochic acid and bovine serum albumin (BSA) under physiological conditions was investigated by fluorescence quenching methods. The results indicate that there is a strong interaction between aristolochic acid and BSA, and the distances between the binding location and tryptophan residue is 2.8 nm. The binding location of aristolochic acid in BSA is in subdomain III A. In addition, the effects of aristolochic acid on the protein second structure were studied using CD and FTIR techniques. The results of CD proved that the alpha-helix contents of BSA decreased from 43.5% to 36.7% after binding with aristolochic acid.

Animals↗
PubMed2000

Pressurized liquid extraction of berberine and aristolochic acids in medicinal plants.

Berberine and aristolochic acids I and II present naturally in medicinal plants were extracted using a laboratory-made pressurized liquid extraction (PLE) system in the dynamic mode. As the target analytes were present naturally in the medicinal plants, spiking was not done and comparison with ultrasonic extraction and Soxhlet extraction was performed to assess the method accuracy. The effect of temperature, volume of solvent required and particle size were investigated. Method precision (RSD, n=5) between 1.98 and 3.4% was achieved for the extraction of berberine and aristolochic acids I and II in medicinal plants and lower than 8% for lower levels of aristolochic acid II in medicinal plants.

Aristolochic Acids↗