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

A unique type of rapidly progressive interstitial fibosis of the kidney designated Chinese herb nephropathy (CHN) has been reported in Belgian woman after intake of Chinese herbs. CHN contains variable clinical features from progressive renal failure with severe anemia to adult-onset Fanconi's syndrome which have been reported mostly in Asian countries. We are reporting a case of 43 years-old female patient. The patient visited our hospital with symptoms of polyuria, polydipsia and generalized weakness and laboratory investigation showed hypokalemia, hyperchloremic metabolic acidosis, hypophosphatemia consitent with Fanconis's syndrome. We found out her intake of Chinese herbal mixture by history taking. The Fanconi's syndrome seemed to be revrersible but it progressed to renal failure after four months in spite of only ten days intake. Renal biopsy resulted typical findings of aristolochic acid induced nephrophathy. Aristolochic acids were also detected in herbal mixture by high performance chromatography. This case shows variable clinical course of aristolochic acid-induced nephrophathy. It is important to bear in mind that CHN could present variable clinical pattern and herbal mixture that include aristolochic acid should be avoided.
Acidosis ; Adult ; Anemia ; Aristolochic Acids ; Asian Continental Ancestry Group ; Biopsy ; Chromatography ; Female ; Humans ; Hypokalemia ; Hypophosphatemia ; Kidney ; Polydipsia ; Polyuria ; Renal Insufficiency

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

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

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

A HPLC method for limit detection of aristolochic acid A in the Chinese herbs containing aristolochic acid or suspected-containing aristolochic acid and their preparations was established. The samples were analyzed on an Alltima C18 column eluted with methanol-water-acetic acid (68:32:1.5) as the mobile phase. Flow rate was at 1.0 mL x min(-1) and the detection wavelength was at 390 nm. The calibration curve was linear over the range from 0.016 to 0.51 g (r = 0.9993) and LOD was 4 ng. The average recovery was 101.2% with RSD of 2.01%. The procedures of sample preparation were systematically investigated. The contents of aristolochic acid A in Radix et Rhizoma Asari bought from market or drugstore were fluctuated from 3.1 to 26.6 microg x g(-1) and 3 of 11 samples accorded with the quality requirement of current Chinese Pharmacopoeia. Among 15 batches samples of Chinese medicaments, only one sample was found to contain aristolochic acid A. The present investigation shows that the method is sensitive and repeatable and it could be used for the limit detection of aristolochic acid A in the Chinese herbal medicines containing trace amount of aristolochic acid A or suspected-containing aristolochic acid A and their preparations.
Acetic Acid ; chemistry ; Aristolochic Acids ; analysis ; Chromatography, High Pressure Liquid ; methods ; Limit of Detection ; Methanol ; chemistry ; Water ; chemistry