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Names | |
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IUPAC name
8-Methoxy-6-nitrophenanthro[3,4-d][1,3]dioxole-5-carboxylic acid
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Other names
Aristinic acid; Aristolochia yellow; Aristolochic acid A; Aristolochin;Aristolochine; Descresept; Tardolyt;TR 1736
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Identifiers | |
3D model (
JSmol ) |
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ChEMBL | |
ChemSpider | |
KEGG | |
PubChem CID
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UNII | |
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Properties | |
C17H11NO7 | |
Molar mass | 341.275 g·mol−1 |
Appearance | yellow powder |
Melting point | 260 to 265 °C (500 to 509 °F; 533 to 538 K) |
Slightly soluble | |
Hazards | |
NFPA 704 (fire diamond) | |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Aristolochic acids are a family of
Although these compounds are widely associated with kidney problems and urothelial cancers, the use of AA-containing plants for medicinal purposes has a long history, and there is controversy regarding their toxicity. Nevertheless, the FDA has issued warnings regarding consumption of AA-containing supplements.
History
Early medical uses
Aristolochic acid first appeared in Chinese medicine in the 5th century AD, however the Birthwort plants in which it is found are mentioned in ancient Greek and Roman medical texts dating back even earlier. In these ancient times, it was used to treat kidney and urinary problems, as well as gout, snakebites, and a variety of other ailments. It was also considered to be an effective contraceptive. In many of these cases, Birthwort plants, and the aristolochic acids they contain, were just some of the many ingredients used to create ointments or salves. In the early 1st century, in Roman texts, aristolochic acids are first mentioned as a component of frequently ingested medicines to treat things such as asthma, hiccups, spasms, pains, and expulsion of afterbirth. [4]
Discovery of toxicity
Aristolochic acid poisoning was first diagnosed at a clinic in Brussels, Belgium, when cases of nephritis leading to rapid kidney failure were seen in a group of women who had all taken the same weight-loss suplement, Aristolochia fangchi, which contained aristolochic acid. This nephritis was termed “Chinese Herbs Nephropathy” (CHN) due to the origin of the weight-loss supplement.[5] It was later discovered that a similar condition previously known as Balkan endemic nephropathy (BEN), first characterized in the 1950’s in southeastern Europe, was also the result of aristolochic acid (AA) consumption. BEN is more slowly progressive than the nephritis that is seen in CHN, but is likely caused by low-level AA exposure, possibly from contamination of wheat flour seeds by a plant of the Birthwort family, Aristolochia clematitis.[6] CHN and BEN fall under the umbrella of what is now known as Aristolochic Acid Nephropathy (AAN), the prevalent symptom of AA poisoning.[5]
Biosynthesis
The aristolochic acids are among a group of substituted 10-nitro-1-phenantropic acids, biogenetically derived from
Symptoms and diagnosis
Exposure to aristolochic acid is associated with a high incidence of
If a patient is thought to have AAN, this can be confirmed through phytochemical analysis of plant products consumed and detection of aristolochic acid
Pharmacology
ADME
Absorption
Once orally ingested, aristolochic acid I is absorbed through the gastrointestinal track into the blood stream.[6]
Distribution
It is distributed throughout the body via the blood stream.[6]
Metabolism
Aristolochic acids are metabolized by oxidation and reduction pathways, or
Excretion
Excretion of aristolochic acids and their metabolites is through the urine. [6]
Mechanism of action
The exact mechanism of action of aristolochic acid is not known, especially in regards to nephropathy. It is thought that the carcinogenic effects of aristolochic acids are a result of mutation of the tumor supressor gene TP53, which seems to be unique to aristolochic acid associated carcinogenesis. [13] Nephropathy caused by aristolochic acid consumption is not mechanistically understood, however DNA adducts characteristic of aristolochic acid induced mutations are found in the kidneys of aristolochic acid nephropathy (AAN) patients, indicating that these might play a role.[13]
Regulation
In April 2001, the Food and Drug Administration issued a consumer health alert warning against consuming botanical products, sold as "traditional medicines" or as ingredients in dietary supplements, containing aristolochic acid.[15] The agency warned that consumption of aristolochic acid-containing products was associated with "permanent kidney damage, sometimes resulting in kidney failure that has required kidney dialysis or kidney transplantation. In addition, some patients have developed certain types of cancers, most often occurring in the urinary tract."[15]
In August 2013, two studies identified an aristolochic acid mutational signature in upper urinary tract cancer patients from Taiwan.[16][17] The carcinogenic effect is the most potent found thus far, exceeding the amount of mutations in smoking-induced lung cancer and UV-exposed melanoma. Exposure to aristolochic acid may also cause certain types of liver cancer.[16]
Controversy
Due to the prevalence of aristolochic acid containing plants in
See also
References
- ISBN 978-0-444-52171-2.)
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: CS1 maint: multiple names: authors list (link - ^ Scarborough, John (2011). "Ancient Medicinal Use of Aristolochia: Birthwort's Tradition and Toxicity". Pharmacy in History. 53 (1): 3–21. Retrieved 3 May 2015.
- ^ )
- ^ a b c d e f g h Lunn, Ruth; Jameson, C.W.; Jahnke, Gloria (2 Sep 2008). "Report on Carcinogens Background Document for Aristolochic Acids" (PDF). National Toxicology Program. Retrieved 3 May 2015.
- doi:10.1139/v69-070
- ISBN 978-1-4160-4252-5.)
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- ^ a b c Go¨kmen, M. Refik; Cosyns, Jean-Pierre; Arlt, Volker M.; Stiborova, Marie; Phillips, David H.; Schmeiser, Heinz H.; Simmonds, Monique S.J.; Cook, Terence; Vanherweghem, Jean-Louis; Nortier, Joe¨lle L.; Lord, Graham M. (2013). "The Epidemiology, Diagnosis, and Management of Aristolochic Acid Nephropathy: A Narrative Review" (PDF). Annals of Internal Medicine. 158 (6): 469–477. Retrieved 3 May 2015.
- ^ a b "Plants Containing Aristolochic Acid" (PDF). IARC Monographs-100A: 347–361. Retrieved 3 May 2015.
- ^ a b FDA Warns Consumers to Discontinue Use of Botanical Products that Contain Aristolochic acid. April 11, 2001.
- ^ PMID 23926199.
- PMID 23926200.
- ^ Dharmananda, Subhuti. "Are Aristolochia Plants Dangerous?". ITM. Institute for Traditional Medicine. Retrieved 3 May 2015.
Further reading
- Aronson, J.K. (2008). "Aristolochicae". Meyler's side effects of herbal medicines. Elsevier. p. 55. ISBN 978-0-444-53269-5.
- Mills, Simon & Bone, Kerry (2005). "Aristolochic Acid Nephropathy". The essential guide to herbal safety. Elsevier Health Sciences. p. 15. ISBN 978-0-443-07171-3.)
{{cite book}}
: CS1 maint: multiple names: authors list (link - Wing-Tat Poon, Chi-Kong Lai, Albert Yan-Wo Chan, 2007. "Aristolochic Acid Nephropathy: The Hong Kong Perspective." Hong Kong Journal of Nephrology, 9(1):7-14.
External links
- Complete list of warnings from the US Food and Drug Administration
- FDA Concerned About Botanical Products, Including Dietary Supplements, Containing Aristolochic Acid May 2000.
- Plants Containing Aristolochic Acid
- Herbal medicines causing kidney failure, bladder cancer in India, Times of India, Mar 19, 2013
Category:IARC Group 1 carcinogens
Category:Nitro compounds
Category:Phenol ethers
Category:Carboxylic acids