Aristolochic Acids ; adverse effects ; Humans ; Kidney Diseases ; chemically induced

Aristolochic Acids ; adverse effects ; Drugs, Chinese Herbal ; adverse effects ; Humans ; Plants, Medicinal ; Quality Control ; Research Design

Aristolochic Acids ; adverse effects ; Child ; Drugs, Chinese Herbal ; adverse effects ; Female ; Humans ; Male ; Nephrosis ; chemically induced

OBJECTIVE: To evaluate the changes in renal oxygenation in rats with acute aristolochic acid nephropathy using blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) at 7.0T. METHODS: Wistar rats were randomly divided into AAN group (=18) and control group (=6) for intraperitoneal injections of AAI at 40 mg/kg and PEG400, respectively, on a daily basis for 6 consecutive days. All the control rats and 6 rats from AAN group underwent BOLD MRI scan before and at 2, 4, and 6 days after the initial injection for measuring renal cortical and medullary R2 values. At each of the 4 time points, 3 rats in AAN group were sacrificed for histological evaluation; the control rats were examined at 6 days after the initial injection. RESULTS: The cortical and medullary R2 values of the rats in AAN group on days 4 and 6 were significantly higher than those in the control group ( < 0.05). In AAN group, the cortical R2 values showed no obvious changes on day 2 as compared with the baseline values, but increased significantly on day 4 ( < 0.05) and day 6 ( < 0.01); the medullary R2 values increased progressively and were significantly higher than the baseline values on day 4 ( < 0.01) and day 6 ( < 0.01). In the control group, no significant changes were detected in either cortical or medullary R2 values throughout the experiment. CONCLUSIONS BOLD MRI allows non-invasive measurement of renal oxygenation levels in rats with AAN. The increase of renal cortical and medullary R2 values, and particularly the latter, indicates a lowered renal oxygenation level, which provides potentially useful information for clinical decisions.
Animals ; Aristolochic Acids ; Kidney ; Kidney Diseases ; metabolism ; Magnetic Resonance Imaging ; Oxygen ; Random Allocation ; Rats ; Rats, Wistar

Aristolochia ; chemistry ; poisoning ; Aristolochic Acids ; analysis ; isolation & purification ; poisoning ; Drugs, Chinese Herbal ; poisoning ; Poisoning ; prevention & control

This paper was aim to screen microorganisms with attenualed efficiency for Chinese medicine containing aristolochic acid A by liquid-state fermentation. Twelve Chinese medicine were detected by UPLC and aristolochic acid A was only founded in four species of Aristolochia, those were Caulis Aristolochiae Manshuriensis, Aristolochiae Radix, Aistolochia Contorta Bunge and Herba Aristolochiae Mollissima,but not in the others. With the four Chinese medicine containing aristolochic acid A as raw material, ten microorganisms were tested, and the content of aristolochic acid A was detected by UPLC. The results showed that one microorganism can decrease content of aristolochic acid A in all those four Chinese medicine.
Aristolochic Acids ; analysis ; metabolism ; Bacteria ; metabolism ; Biotransformation ; Drugs, Chinese Herbal ; analysis ; metabolism ; Fungi ; metabolism ; Plants, Medicinal ; chemistry ; microbiology

OBJECTIVETo investigate whether aristolochic acid can be transported into human kidney proximal tubular cell (HKC) and its potential mechanism.

METHODSIntracellular aristolochic acid was measured by liquid chromatography-tandem mass spectrometry. The release of lactate dehydrogenase (LDH) induced by aristolochic acid in the presence of organic anion transporter inhibitor (probenecid) or organic cation transporter inhibitor (tetraethylammonium) was evaluated. The effects of probenecid on aristolochic acid induced connective tissue growth factor (CTGF) mRNA and protein expression were also examined by real time polymerase chain reaction and Western blot, respectively.

RESULTSAristolochic acid was detected in the suspension of the denatured HKC after incubation with aristolochic acid sodium salt. The release of LDH from HKC, which was induced by 60 mg/L aristolochic acid sodium salt, was significantly inhibited by 1 mmol/L probenecid (P < 0.01), but not by 1 mmol/L tetraethylammonium. The increased CTGF mRNA and protein expression in HKC stimulated by 40 mg/L aristolochic acid sodium salt was significantly down-regulated by 1 mmol/L probenecid (P < 0.05), with an inhibition rate of 16% and 21%, respectively.

CONCLUSIONAristolochic acid can be transported into HKC by organic anion transport system, and then exerts its biological effects.

Aristolochic Acids ; metabolism ; Connective Tissue Growth Factor ; metabolism ; Epithelial Cells ; metabolism ; Humans ; Kidney ; physiology ; Organic Anion Transporters ; metabolism

Aristolochic Acids ; adverse effects ; Drugs, Chinese Herbal ; adverse effects ; Humans ; Kidney Tubular Necrosis, Acute ; chemically induced ; prevention & control

OBJECTIVETo develop an HPLC method for determination of the plasma concentration of aristolochic acid I (AA I ) and aristolochic acid II (AA II) and study their pharmacokinetics in rats.

METHODThe plasma samples were extracted with acetonitrile. The analysis involved a C18 column as stationary phase and methanol, water and acetic acid as mobile phase. The flow rate was 1.0 mL min(-1), the UV detection wavelength was 315 nm. After a single intravenous dose of 5 mg kg(-1) AA in rats, the pharmacokinetic parameters were estimated.

RESULTThe calibration curve of AA I was linear over the range from 0.056 mg L(-1) to 56.3 mg L(-1) with a correlation coefficient of 0.9997. The mean recovery rate was 88.7%. The RSD of within-day and between-day were all less than 8%. And the calibration curve of AA II was linear over the range from 0.192 mg L(-1) to 11.52 mg L(-1) with a correlation coefficient of 0. 998 9. The mean recovery was 85.8%. The RSD of within-day was less than 3% and between-day was less than 10%. The main pharmacokinetic parameters were estimated to be as follows: CL = (0.010 +/- 0.003) L min(-1) kg(-1), t(1/2alpha) = (8.2 +/- 1.7) min, t(1/2beta) = (79.6 +/- 28.5) min for AA I; CL = (0.003 +/- 0.001) L min(-1) kg (-1), t(1/2alpha) = (56.7 +/- 38.1) min, t(1/2beta) = (209.3 +/- 37.9) min for AA II.

CONCLUSIONThe established HPLC method is simple and sensitive to determine the concentration of AA I , AA II and the metabolite of AA I in rat plasma. From the result of animal's test, we can find that AA I was quickly eliminated from plasma, the elimination of AA II and Aristololactam-the metabolite of AA I - were slower than that of AA I.

Animals ; Aristolochic Acids ; pharmacokinetics ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; pharmacokinetics ; Male ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results

OBJECTIVETo develop a HPLC method to determine the contents of aristolochic A in aristolochia debilis and Asarun spp..

METHODMethanol-water-formic acid extracts were separated on an Alltech C18 column with methanol-water-acetic acid (68:32:1) as mobile phase. The flow rate was 1.0 mL x min(-1). UV detection wavelength was 390 nm. Column temperature was 35 degrees C.

RESULTAristolochic acid A was separated well. The relationship of injection amounts and peak areas was linear (r = 0.9999) the range of 0.12-1.89 microg x g(-1) and the recovery rate was 101.8% (n = 5). 11 samples of aristolochia debilis which bought from different areas in China were determined, and the contents of aristolochic acid A varied from 0.9 to 2 mg x g(-1). The difference of the contents in Asarum spp. was obvious. The highest is 0.35, and aristolochic acid A couldn't be detected in one sample.

Aristolochia ; chemistry ; Aristolochic Acids ; analysis ; Asarum ; chemistry ; China ; Chromatography, High Pressure Liquid ; methods ; Ecosystem ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry