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Revision as of 09:42, 7 February 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers from ChemSpider, CommonChemistry and FDA for the Chem/Drugbox validation project - Updated: ChEMBL KEGG.← Previous edit		Latest revision as of 23:56, 16 December 2024 edit undoArthurfragoso (talk | contribs)Extended confirmed users2,076 edits Fixes images on dark mode
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	{{chembox		{{chembox
	| Watchedfields = changed		| Watchedfields = changed
	| verifiedrevid = 399531133		| verifiedrevid = 412505426
	| Name = '''Aristolochic acid'''		| Name = Aristolochic acid I
	| ImageFile_Ref = {{chemboximage|correct|??}}		| ImageFile_Ref = {{chemboximage|correct|??}}
	| ImageFile = Aristolochic acid.png		| ImageFile = Aristolochic acid.png
	| ImageSize = 178px		| ImageSize = 160px
			| ImageClass = skin-invert
	| IUPACName =8-methoxy-6-nitrophenanthrodioxole-5-carboxylic acid
	| OtherNames = Aristolochic acid I		| ImageFile1 = Aristolochic-acid-3D-spacefill.png
			| ImageSize1 = 180px
	*Aristinic acid
			| ImageName1 = C=black, H=white, O=red, N=blue
	*Aristolochia yellow
	*Aristolochic acid A		| ImageAlt1 = Aristolochic acid molecule
			| PIN =8-Methoxy-6-nitro-2''H''-phenanthrodioxole-5-carboxylic acid
	*Aristolochin
			| OtherNames = Aristinic acid; Aristolochia yellow; Aristolochic acid A; Aristolochin;Aristolochine; Descresept; Tardolyt;TR 1736
	*Aristolochine
			|Section1={{Chembox Identifiers
	*Descresept
			| PubChem = 2236
	*Isoaristolochic acid
			| KEGG_Ref = {{keggcite|correct|kegg}}
	*Tardolyt
	*TR 1736
	Aristolochic acid II
	*Aristolochic acid B
	| Section1 = {{Chembox Identifiers
	| PubChem = 2236
	| KEGG = C08469		| KEGG = C08469
	| InChI = 1/C17H11NO7/c1-23-12-4-2-3-8-9(12)5-11(18(21)22)14-10(17(19)20)6-13-16(15(8)14)25-7-24-13/h2-6H,7H2,1H3,(H,19,20)		| InChI = 1/C17H11NO7/c1-23-12-4-2-3-8-9(12)5-11(18(21)22)14-10(17(19)20)6-13-16(15(8)14)25-7-24-13/h2-6H,7H2,1H3,(H,19,20)
	| InChIKey = BBFQZRXNYIEMAW-UHFFFAOYAG		| InChIKey = BBFQZRXNYIEMAW-UHFFFAOYAG
			| ChEMBL_Ref = {{ebicite|correct|EBI}}
	| ChEMBL = 93353		| ChEMBL = 93353
	| StdInChI_Ref = {{stdinchicite|correct|chemspider}}		| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
Line 29:		Line 25:
	| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}		| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChIKey = BBFQZRXNYIEMAW-UHFFFAOYSA-N		| StdInChIKey = BBFQZRXNYIEMAW-UHFFFAOYSA-N
			| CASNo_Ref = {{cascite|correct|??}}
	| CASNo = 313-67-7		| CASNo = 313-67-7
	| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}		| UNII_Ref = {{fdacite|correct|FDA}}
			| UNII = 94218WFP5T
			| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
	| ChemSpiderID = 2149		| ChemSpiderID = 2149
	| SMILES = (=O)c1cc4c(c2c1c(C(=O)O)cc3OCOc23)cccc4OC		| SMILES = (=O)c1cc4c(c2c1c(C(=O)O)cc3OCOc23)cccc4OC
	}}		}}
	| Section2 = {{Chembox Properties		|Section2={{Chembox Properties
			| Appearance = yellow powder
	|C=17|H=11|N=1|O=7
			| C =17|H=11|N=1|O=7
	| MolarMass = 341.27684 g/mol
	| Density = 1.571g/cm<sup>3</sup>		| Density =
	| MeltingPt = 260 - 265 °C		| MeltingPtC = 260 to 265
			| MeltingPt_notes =
	| BoilingPt = 615.5°C @760mmHg
	| Solubility = DMSO		| BoilingPt =
	| Solubility = slightly soluble in water		| Solubility = Slightly soluble
	}}		}}
			|Section3={{Chembox Hazards
	| Appearence = yellow powder
			| NFPA-H = 2
	| Section3 = {{Chembox Hazards
	| FlashPt = 326°C		| NFPA-F = 1
			| NFPA-R = 0
			| NFPA-S =
			| FlashPt =
	}}		}}
	}}		}}
			'''Aristolochic acids''' ({{IPAc-en|lang|ə|ˌ|r|ɪ|s|t|ə|ˈ|l|oʊ|k|ᵻ|k}}) are a family of ], ], and ] ] commonly found in the ] family ] (birthworts). Aristolochic acid (AA) I is the most abundant one.<ref>{{cite book|chapter=Chemical constituents and pharmacology of ''Aristolochia'' species|editor=Rahman, Atta-ur|title=Studies in Natural Products Chemistry: Bioactive Natural Products (Part L)|publisher=Gulf Professional Publishing|year=2005|isbn=978-0-444-52171-2|page=863|chapter-url=https://books.google.com/books?id=UBHng8FfwgIC&pg=PA863|author=Wu, Tian-Shung|display-authors=etal }}</ref> The family Aristolochiaceae includes the genera '']'' and '']'' (wild ginger), which are commonly used in ].<ref>{{cite journal |vauthors=Heinrich M, Chan J, Wanke S, Neinhuis C, Simmonds MS |title=Local uses of Aristolochia species and content of nephrotoxic aristolochic acid 1 and 2--a global assessment based on bibliographic sources |journal=J Ethnopharmacol |volume=125 |issue=1 |pages=108–44 |date=August 2009 |pmid=19505558 |doi=10.1016/j.jep.2009.05.028 }}</ref><ref>{{cite book|chapter=Mechanisms of drug-induced nephrotoxicity|editor=Uetrecht, Jack|title=Adverse Drug Reactions|publisher=Springer|year=2010|isbn=978-3-642-00662-3|page=123|chapter-url=https://books.google.com/books?id=0NhAFmL2Q08C&pg=PA123|author1=Nolin, Thomas D. |author2=Himmelfarb, Jonathan |name-list-style=amp }}</ref> Although these compounds are widely associated with kidney problems, liver and urothelial cancers, the use of AA-containing plants for medicinal purposes has a long history. The ] has issued warnings regarding consumption of AA-containing supplements.
	'''Aristolochic acid''' is a ] found in '']'' and '']'', both in the ] family of ]s. Aristolochic acid is composed of a ~1:1 mixture of two forms, aristolochic acid I and aristolochic acid II. In type II, the –OCH<sub>3</sub> group is replaced with –H.
			==History==
	In addition to its carcinogenicity, aristolochic acid is also highly ] and may be a causative agent in ]. Aristolochic acid is linked to increase in urinary tract cancers as well. However, despite these well-documented dangers, aristolochic acid still is present sometimes in ] (such as for weight loss), primarily because of substitution of innocuous herbs with ''Aristolochia'' species.
			===Early medical uses===
	The following substitutions (not a complete list) with ''Aristolochia'' species have been reported:
			Birthwort plants, and the aristolochic acids they contain, were quite common in ancient Greek and Roman medical texts, well-established as an herb there by the fifth century BC.<ref name= "scarborough">{{cite journal|last1=Scarborough|first1=John|title=Ancient Medicinal Use of Aristolochia: Birthwort's Tradition and Toxicity|journal=Pharmacy in History|date=2011|volume=53|issue=1|pages=3–21|url=https://www.academia.edu/3219887|access-date=3 May 2015|pmid=22702021}}</ref> Birthworts appeared in Ayurvedic texts by 400 AD, and in Chinese texts later in the fifth century. 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, birthworts were just some of the many ingredients used to create ointments or salves. In the early first 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 ].<ref name= "scarborough"/>
			===Discovery of toxicity===
	* '']'' (reported in Belgium).
			====Kidney damage====
	* ''Solanum lyratum'' 白毛藤 báimáoténg (pak mo tang), also known as 白英 báiyīng (reported in Hong Kong).
			Aristolochic acid poisoning was first diagnosed at a clinic in Brussels, Belgium, when cases of ] leading to rapid kidney failure were seen in a group of women who had all taken the same weight-loss supplement, ''Aristolochia fangchi'', which contained aristolochic acid.<ref name=Shaw2010>{{cite journal|last1=Shaw|first1=D|title=Toxicological risks of Chinese herbs.|journal=Planta Medica|date=December 2010|volume=76|issue=17|pages=2012–8|doi=10.1055/s-0030-1250533|pmid=21077025|doi-access=free}}</ref> This nephritis was termed “Chinese herbs nephropathy” (CHN) due to the origin of the weight-loss supplement.<ref name="seven">{{cite journal|last1=Arlt|first1=Volker|last2=Stiborova|first2=Marie|last3=Schmeiser|first3=Heinz|title=Aristolochic acid as a probable human cancer hazard in herbal remedies: a review|journal=Mutagenesis|date=2002|volume=17|issue=4|pages=265–277|doi=10.1093/mutage/17.4.265|pmid=12110620|doi-access=free}}<!--|accessdate=3 May 2015--></ref> A similar condition previously known as ] (BEN), first characterized in the 1950s in southeastern Europe, was later discovered to be 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, '']''.<ref name="six">{{cite journal|last1=Lunn|first1=Ruth|last2=Jameson|first2=C.W.|last3=Jahnke|first3=Gloria|title=Report on Carcinogens Background Document for Aristolochic Acids|journal=National Toxicology Program|date=2 Sep 2008|url=https://ntp.niehs.nih.gov/ntp/roc/twelfth/2010/finalbds/aristolochic_acids_final_508.pdf |access-date=3 May 2015}}</ref> CHN and BEN fall under the umbrella of what is now known as aristolochic acid nephropathy, the prevalent symptom of AA poisoning.<ref name="seven" />
	* Various ''Akebia'' species (Akebiae Caulis) 木通 mùtōng (reported in Mainland China).
			]
			====Liver cancer====
			A study reported in the ] journal in October 2017 reported high incidents of liver cancer in Asia, particularly Taiwan, which bore the "well-defined mutational signature" of aristolochic acids. The same link was found in Vietnam and other South-east Asian countries. This was compared with much lower rates found in Europe and North America.<ref>{{cite news|newspaper=Hong Kong Free Press|url=https://www.hongkongfp.com/2017/10/19/across-asia-liver-cancer-linked-herbal-remedies-study/|title=Across Asia, liver cancer is linked to herbal remedies – study|date=19 October 2017|access-date=20 October 2017}}</ref>
			==Biosynthesis==
			The herbal drug known as aristolochic acid contains a mixture of numerous structurally related nitrophenanthrene carboxylic acids generally consisting of two major compounds: aristolochic acid I (AA-I) and aristolochic acid II (AA-II). The biosynthesis of these compounds has been of considerable interest due in large part to the inclusion of both an aryl carboxylic acid and an aryl nitro functionality (uncommon in natural products) within their structures, which suggested an apparent biogenetic relationship to the well-known aporphine alkaloids.<ref>{{Cite journal|last1=Spenser|first1=I. D.|last2=Tiwari|first2=H. P.|date=1966|title=Biosynthesis of Aristolochic Acid|journal=Chemical Communications|publisher=Royal Society of Chemistry|issue=2|pages=55–56|doi=10.1039/c19660000055}}</ref> Furthermore, this association thereby suggested a biosynthetic relationship with norlaudanosoline (]) or related ] precursors, which in turn are derived from ] (2).<ref name=":0">{{Citation
			| title = Biosynthesis of aristolochic acid | year = 1969 | journal = Canadian Journal of Chemistry | pages = 481–487 | volume = 47 | issue = 3 | last1 = Comer | first1 = F. | last2 = Tiwari | first2 = H.P.
			| last3 = Spenser | first3 = I.D. | doi=10.1139/v69-070}}</ref> Feeding studies (''Aristolochia sipho'') independently using uniquely <sup>14</sup>C-labeled compounds -tyrosine, -dopamine and -dihydroxyphenylalanine resulted in the isolation of -AA-I in each case, which illustrated that the aporphine alkaloid stephanine (11) could be a precursor of AA-I since tyrosine, L-DOPA (3) and dopamine (4) were known precursors of norlaudanosoline: tyrosine (2) is metabolized to ] (3) which is converted into ] (4) which is metabolized to ] (DOPAL); cyclization of these two compounds results in the formation of ] via a ] like condensation catalyzed by norlaudanosoline synthetase.<ref>{{Cite journal|last1=Rueffer|first1=Martina|last2=El-Shagi|first2=Hannemarie|last3=Nagakura|first3=Naotaka|last4=Zenk|first4=Meinhart H.|date=1981|title=(S)-Norlaudanosoline synthase: The first enzyme in the benzylisoquinoline biosynthetic pathway|journal=FEBS Letters|volume=129|pages=5–9|doi=10.1016/0014-5793(81)80742-9|s2cid=13456773}}</ref><ref>{{Citation | title = Biotransformation of Dopamine to Norlaudanosoline by Aspergillus niger | year = 1991 | journal = Biotechnology and Bioengineering | pages = 1029–1033 | volume = 38
			| issue = 9 | last1 = Hoover | first1 = Larry K. | last2 = Moo-young | first2 = Murray
			| last3 = Legge | first3 = Raymond L. | doi=10.1002/bit.260380911| pmid = 18600867 | s2cid = 27365169 }}</ref>
			Subsequent feeding studies that used (±)‑-norlaudanosoline also resulted in the formation of <sup>14</sup>C‑labeled-AAI, further suggesting that norlaudanosoline and stephanine (11) could have a possible intermediacy in the biosynthesis of AA-I. Degradation studies of the isolated <sup>14</sup>C-labeled AA-I demonstrated that the carbon atom at ring position C4 of the benzyltetrahydroisoquinoline norlaudanosoline was incorporated exclusively in the carboxylic acid moiety of AAI. When this study was repeated but using -tetrahydropapaverine no labeled AAI was isolated; this observation established that a phenol oxidative reaction was required for the biosynthesis of AA-I from norlaudanosoline, further supporting the intermediacy of aporphine intermediates.<ref>{{Cite journal|last1=Schutte|first1=H. R.|last2=Orban|first2=U.|last3=Mothes|first3=K.|date=1967|title=Biosynthesis of Aristolochic Acid|journal=European Journal of Biochemistry|volume=1|issue=1|pages=70–72|doi=10.1111/j.1432-1033.1967.tb00045.x|pmid=6059349|doi-access=free}}</ref> The results of a feeding experiment (''A. sipho'') with (±)‑-tyrosine followed by degradation of the isolated doubly labeled AA-I provided evidence that the nitro group of AA-I originates from the amino group of tyrosine.<ref name=":0" />
			Confirmation of the involvement of aporphine intermediates in the biogenetic route from norlaudanosoline to AA-I was obtained some two decades later through a series of feeding studies (''Aristolochia bracteata'') using several labeled hypothetical benzyltetrahydroisoquinoline and aporphine precursors.<ref name=":1">{{Citation|last1=Sharma|first1=Vidur|title=Biosynthesis of aristolochic acid|journal=Journal of the Chemical Society, Perkin Transactions 1|volume=1|pages=1153–1155|year=1982|doi=10.1039/p19820001153|last2=Jain|first2=Sudha|last3=Bhakuni|first3=Dewan S.|last4=Kapil|first4=Randhir S.}}</ref> Feeding experiments with (±)‑-nororientaline resulted in the isolation of the doubly labeled AA-I. Cleavage of the methylenedioxy group with trapping of the resulting <sup>14</sup>C‑labeled formaldehyde confirmed that this functionality was formed from the ''o''‑methoxyphenol segment of the tetrahydroisoquinoline ring of nororientaline. (±)‑‑Orientaline was also incorporated into AA-I. These observations implied that the aporphine prestephanine (10) would be an obligatory intermediate in the biosynthesis, which would involve the intermediacy of the proaporphines orientalinone (8) and orientalinol (9) via the known intramolecular dienone-dienol-phenol sequence for the transformation of benzyltetrahydroisoquinolines to aporphines.<ref>{{Cite journal|last1=Battersby|first1=A. R.|last2=Brown|first2=R. T.|last3=Clements|first3=J. H.|last4=Iverach|first4=G.|date=1965|title=On the Biosynthesis of Isothebaine|journal=Chemical Communications|issue=11|publisher=Royal Society of Chemistry|pages=230–232|doi=10.1039/c19650000230}}</ref> A potential role for CYP80G2, a cytochrome P450 that has been demonstrated to catalyze the intramolecular C-C phenol coupling of several benzyltetrahydroisoquinolines, in this orientaline (7) to prestephanine (10) transformation has been suggested.<ref>{{Cite journal|last1=Ikezawa|first1=Nobuhiro|last2=Iwasa|first2=Kinuko|last3=Sato|first3=Fumihiko|date=2008|title=Molecular Cloning and Characterization of CYP80G2, a Cytochrome P450 That Catalyzes an Intramolecular C-C Phenol Coupling of (S)-Reticuline in Magnoflorine Biosynthesis, from Cultured Coptis japonica Cells|journal=Journal of Biological Chemistry|volume=283|issue=14|pages=8810–8821|doi=10.1074/jbc.M705082200|pmid=18230623|doi-access=free}}</ref> (±)‑‑Prestephanine was incorporated into AA-I confirming its intermediacy in the biosynthesis; and also (±)‑‑stephanine was incorporated into AA-I.<ref name=":1" /> This final transformation, that is stephanine (11) to AA-I (12), involves an uncommon oxidative cleavage of the B ring of the aporphine structure to give a nitro substituted phenanthrene carboxylic acid. Hence, taken together these experiments support the sequence outlined for the biosynthesis of aristolochic acid I from norlaudanosoline.
			]
			==Symptoms and diagnosis==
			Exposure to aristolochic acid is associated with a high incidence of ] ],<ref>{{cite book|editor=Ronco, Claudio |display-editors=etal |title=Critical care nephrology|publisher=Elsevier Health Sciences|year=2008|isbn=978-1-4160-4252-5|page=1699|url=https://books.google.com/books?id=XkKn96HThzEC&pg=PA1699}}</ref> and is linked to urothelial cancer.<ref>{{cite journal |vauthors=Chen CH, Dickman KG, Moriya M, Zavadil J, Sidorenko VS, Edwards KL, Gnatenko DV, Wu L, Turesky RJ, Wu XR, Pu YS, Grollman AP |title=Aristolochic acid-associated urothelial cancer in Taiwan |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=109 |issue=21 |pages=8241–6 |date=May 2012 |pmid=22493262 |pmc=3361449 |doi=10.1073/pnas.1119920109 |doi-access=free }}</ref><ref>{{Cite journal | doi = 10.1093/jnci/djp467 | pmid = 20026811 | title = Population-Based Case-Control Study of Chinese Herbal Products Containing Aristolochic Acid and Urinary Tract Cancer Risk | year = 2009 | last1 = Lai | first1 = M.-N. | last2 = Wang | first2 = S.-M. | last3 = Chen | first3 = P.-C. | last4 = Chen | first4 = Y.-Y. | last5 = Wang | first5 = J.-D. | journal = JNCI Journal of the National Cancer Institute | volume = 102 | issue = 3 | pages = 179–186| pmc = 2815723 }}</ref> Since aristolochic acid is a mutagen, it does damage over time. Patients are often first diagnosed with aristolochic acid ] (AAN), which is a rapidly progressive nephropathy and puts them at risk for renal failure and urothelial cancer. However, urothelial cancer is only observed long after consumption. One study estimated, on average, detectable cancer develops ten years from the start of daily aristolochic acid consumption.<ref name="seven"/>
			A patient thought to have AAN can be confirmed through phytochemical analysis of plant products consumed and detection of aristolactam ] in the renal cells. (Aristolochic acid is metabolised into aristolactam.) Additionally, mutated proteins in renal cancers as a result of ] of ]:] pairings to T:A are characteristically seen in aristolochic acid-induced mutations. In some cases, early detection resulting in cessation of aristolochia-product consumption can lead to reverse of the kidney damage.<ref name="six"/><ref name="five">{{cite journal|last1=Go¨kmen|first1=M. Refik|last2=Cosyns|first2=Jean-Pierre|last3=Arlt|first3=Volker M.|last4=Stiborova|first4=Marie|last5=Phillips|first5=David H.|last6=Schmeiser|first6=Heinz H.|last7=Simmonds|first7=Monique S.J.|last8=Cook|first8=Terence|last9=Vanherweghem|first9=Jean-Louis|last10=Nortier|first10=Joe¨lle L.|last11=Lord|first11=Graham M.|title=The Epidemiology, Diagnosis, and Management of Aristolochic Acid Nephropathy: A Narrative Review|journal=Annals of Internal Medicine|date=2013|volume=158|issue=6|pages=469–477|url=https://dipot.ulb.ac.be/dspace/bitstream/2013/176399/1/Gokmen.pdf|access-date=3 May 2015|doi=10.7326/0003-4819-158-6-201303190-00006|pmid=23552405|s2cid=8007069}}</ref>
			==Pharmacology==
			===Absorption, distribution, metabolism, and excretion===
			Once orally ingested, aristolochic acid I is absorbed through the gastrointestinal tract into the blood stream.<ref name="six"/> It is distributed throughout the body via the blood stream.<ref name="six"/>
			]
			Aristolochic acids are metabolized by oxidation and reduction pathways, or ]. Reduction of aristolochic acid I produces aristolactam I<ref>{{cite journal |doi=10.1039/c3np70114j |title=Naturally occurring aristolochic acid analogues and their toxicities |year=2014 |last1=Michl |first1=Johanna |last2=Ingrouille |first2=Martin J. |last3=Simmonds |first3=Monique S. J. |last4=Heinrich |first4=Michael |journal=Natural Product Reports |volume=31 |issue=5 |pages=676–93 |pmid=24691743 }}</ref> which has been observed in the urine. Further processing of aristolactam I by O-demethylation results in aristolactam Ia, the primary metabolite.<ref name="six"/><ref name="four">{{cite journal|title=Plants Containing Aristolochic Acid|journal=IARC Monographs-100A|pages=347–361|url=http://monographs.iarc.fr/ENG/Monographs/vol100A/mono100A-23.pdf|access-date=3 May 2015}}</ref> Additionally, nitroreduction results in an N-acylnitrenium ion, which can form DNA-base adducts, thus giving aristolochic acid I its mutagenic properties.<ref name="seven"/><ref name="six"/><ref name="four"/>
			Aristolactam I adducts that are bound to DNA are extremely stable; they have been detected in patient biopsy samples taken 20 years after exposure to plants containing aristolochic acid.<ref>{{cite journal|title=Exceptionally long-term persistence of DNA adducts formed by carcinogenic aristolochic acid I in renal tissue from patients with aristolochic acid nephropathy|journal=International Journal of Cancer|volume=135|issue=2|doi=10.1002/ijc.28681|pmid=24921086|date=2014|last1=Schmeiser|last2=Nortier|last3=Singh|last4=da Costa|last5=Sennesaei|last6=Cassuto-Viguier|last7=Ambrosetti|last8=Rorive|last9=Pozdzik|last10=Phillips|last11=Stiborova|last12=Arlt|pages=502–507|s2cid=28784835|doi-access=free}}</ref>
			Excretion of aristolochic acids and their metabolites is through the urine.<ref name="six"/>
			===Mechanism of action===
			The exact mechanism of action of aristolochic acid is not known, especially in regards to nephropathy. The carcinogenic effects of aristolochic acids are thought to be a result of mutation of the ] '']'', which seems to be unique to aristolochic acid-associated carcinogenesis.<ref name="five"/> Nephropathy caused by aristolochic acid consumption is not mechanistically understood, but DNA adducts characteristic of aristolochic acid-induced mutations are found in the kidneys of AAN patients, indicating these might play a role.<ref name="five"/>
			==Regulation==
			In April 2001, the ] issued a consumer health alert warning against consuming botanical products, sold as "]s" or as ingredients in dietary supplements, containing aristolochic acid.<ref name=2001FDA> April 11, 2001.</ref> 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."<ref name=2001FDA/>
			In August 2013, two studies identified an aristolochic acid mutational signature in upper urinary tract cancer patients from Taiwan.<ref name=Poon>{{cite journal | doi = 10.1126/scitranslmed.3006086 | title = Genome-Wide Mutational Signatures of Aristolochic Acid and Its Application as a Screening Tool | year = 2013 | last1 = Poon | first1 = S. L. | last2 = Pang | first2 = S.-T. | last3 = McPherson | first3 = J. R. | last4 = Yu | first4 = W. | last5 = Huang | first5 = K. K. | last6 = Guan | first6 = P. | last7 = Weng | first7 = W.-H. | last8 = Siew | first8 = E. Y. | last9 = Liu | first9 = Y. | journal = Science Translational Medicine | volume = 5 | issue = 197 | pages = 197ra101 | pmid = 23926199 | s2cid = 25923013 }}</ref><ref>{{cite journal | doi = 10.1126/scitranslmed.3006200 | title = Mutational Signature of Aristolochic Acid Exposure as Revealed by Whole-Exome Sequencing | year = 2013 | last1 = Hoang | first1 = M. L. | last2 = Chen | first2 = C.-H. | last3 = Sidorenko | first3 = V. S. | last4 = He | first4 = J. | last5 = Dickman | first5 = K. G. | last6 = Yun | first6 = B. H. | last7 = Moriya | first7 = M. | last8 = Niknafs | first8 = N. | last9 = Douville | first9 = C. | journal = Science Translational Medicine | volume = 5 | issue = 197 | pages = 197ra102 | pmid = 23926200 | pmc=3973132}}</ref> 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.<ref name=Poon/>
	==See also==		==See also==
	*]		*]
			* ]
			*'']''
	==References==		==References==
			{{reflist|2}}
	* April 11, 2001.
	* May 2000.
			==Further reading==
	* Health Canada advising not to use products labelled to contain Aristolochia. August ]. Website - http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/2001/2001_91_e.html
			* {{cite book|author=Aronson, J.K.|chapter=Aristolochicae|title=Meyler's side effects of herbal medicines|publisher=Elsevier|year=2008|isbn=978-0-444-53269-5|page=55|chapter-url=https://books.google.com/books?id=ibxfK1l6oXoC&pg=PA55}}
	* 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.
			* {{cite book|chapter=Aristolochic Acid Nephropathy|title=The essential guide to herbal safety|publisher=Elsevier Health Sciences|year=2005|isbn=978-0-443-07171-3|page=15|chapter-url=https://books.google.com/books?id=85M0N8UioCcC&pg=PA15|author1=Mills, Simon |author2=Bone, Kerry |name-list-style=amp }}
	*Lai M., 2009. Journal of National Cancer Institute. doi:10.1093/jnci/djp467. (Short summary published as "Chinese herbal products containing aristolochic acid were associated with urinary tract cancer" in "HemOnc today", page 28, dated 2010-01-25.)
			* {{cite journal | last1 = Poon | first1 = Wing-Tat | last2 = Lai | first2 = Chi-Kong | last3 = Yan-Wo Chan | first3 = Albert | year = 2007 | title = Aristolochic Acid Nephropathy: The Hong Kong Perspective | journal = Hong Kong Journal of Nephrology | volume = 9 | issue = 1| pages = 7–14 | doi=10.1016/s1561-5413(07)60003-9| doi-access = }}
	==External links==		==External links==
			{{Commons category|Aristolochic acid}}
	* of warnings from the US ]
			* of warnings from the US ]
	*
			* May 2000.
			*
			* , ''Times of India'', Mar 19, 2013
	{{DEFAULTSORT:Aristolochic Acid}}		{{DEFAULTSORT:Aristolochic Acid}}
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	{{commonscat|Aristolochic acid}}
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