{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T08:38:19Z","timestamp":1792139899258,"version":"4.4.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2004,2,1]],"date-time":"2004-02-01T00:00:00Z","timestamp":1075593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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\u22121 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.<\/jats:p>","DOI":"10.1211\/0022357023051","type":"journal-article","created":{"date-parts":[[2004,2,18]],"date-time":"2004-02-18T23:03:31Z","timestamp":1077145411000},"page":"221-229","source":"Crossref","is-referenced-by-count":121,"title":["Acute nephrotoxicity of aristolochic acids in mice"],"prefix":"10.1093","volume":"56","author":[{"given":"Noriko","family":"Sato","sequence":"first","affiliation":[{"name":"Department of Drug Information and Communication, Graduate School of Pharmaceutical Sciences, Chiba University , 1\u201333, Yayoi-cho, Inage-ku, Chiba 263\u20138522,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Drug Information and Communication, Graduate School of Pharmaceutical Sciences, Chiba University , 1\u201333, Yayoi-cho, Inage-ku, Chiba 263\u20138522,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reiko","family":"Tsuchiya","sequence":"additional","affiliation":[{"name":"Department of Drug Information and Communication, Graduate School of Pharmaceutical Sciences, Chiba University , 1\u201333, Yayoi-cho, Inage-ku, Chiba 263\u20138522,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Mukoyama","sequence":"additional","affiliation":[{"name":"Department of Drug Information and Communication, Graduate School of Pharmaceutical Sciences, Chiba University , 1\u201333, Yayoi-cho, Inage-ku, Chiba 263\u20138522,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-ichi","family":"Yamagata","sequence":"additional","affiliation":[{"name":"Department of Drug Information and Communication, Graduate School of Pharmaceutical Sciences, Chiba University , 1\u201333, Yayoi-cho, Inage-ku, Chiba 263\u20138522,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobunori","family":"Satoh","sequence":"additional","affiliation":[{"name":"Department of Drug Information and Communication, Graduate School of Pharmaceutical Sciences, Chiba University , 1\u201333, Yayoi-cho, Inage-ku, Chiba 263\u20138522,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiro","family":"Ueda","sequence":"additional","affiliation":[{"name":"Department of Drug Information and Communication, Graduate School of Pharmaceutical Sciences, Chiba University , 1\u201333, Yayoi-cho, Inage-ku, Chiba 263\u20138522,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Ming","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University , 250, Wu Hsing Street, Taipei 110,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Ogawa","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine, Chiba University Hospital , 1\u20138\u20131, Inohana, Chuo-ku, Chiba 260\u20138677,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaaki","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Central Research Laboratory, Kotaro Pharmaceutical Co., LTD , 47\u20133, Suga-cho, Takatsuki, Osaka 569\u20130022,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seizo","family":"Kondo","sequence":"additional","affiliation":[{"name":"Central Research Laboratory, Kotaro Pharmaceutical Co., LTD , 47\u20133, Suga-cho, Takatsuki, Osaka 569\u20130022,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2004,2,1]]},"reference":[{"key":"2024103109403472900_cit1","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1093\/mutage\/17.4.265","article-title":"Aristolochic acid as a probable human cancer hazard in herbal remedies: a review","volume":"17","author":"Arlt","year":"2002","journal-title":"Mutagenesis"},{"key":"2024103109403472900_cit2","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1093\/carcin\/18.5.1063","article-title":"32P-post-labelling analysis of DNA adducts formed by aristolochic acid in tissues from patients with Chinese herbs nephropathy","volume":"18","author":"Bieler","year":"1997","journal-title":"Carcinogenesis"},{"key":"2024103109403472900_cit3","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1021\/np50032a017","article-title":"Studies on Aristolochia III. Isolation and biological evaluation of constituents of Aristolochia indicaroots for fertility-regulating activity","volume":"47","author":"Che","year":"1984","journal-title":"J. Nat. Prod."},{"key":"2024103109403472900_cit4","first-page":"29","article-title":"Aristolochia alkaloids","volume":"31","author":"Chen","year":"1987","journal-title":"The Alkaloids"},{"key":"2024103109403472900_cit5","doi-asserted-by":"crossref","first-page":"33","DOI":"10.2165\/00002018-200326010-00004","article-title":"Aristolochic acid and \u2018Chinese herbs nephropathy\u2019: a review of the evidence to date","volume":"26","author":"Cosyns","year":"2003","journal-title":"Drug Saf."},{"key":"2024103109403472900_cit6","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1038\/ki.1994.220","article-title":"Chinese herbs nephropathy: a clue to Balkan endemic nephropathy","volume":"45","author":"Cosyns","year":"1994","journal-title":"Kidney Int."},{"key":"2024103109403472900_cit7","doi-asserted-by":"crossref","first-page":"2164","DOI":"10.1046\/j.1523-1755.2001.00731.x","article-title":"Chronic aristolochic acid toxicity in rabbits: a model of Chinese herbs nephropathy","volume":"59","author":"Cosyns","year":"2001","journal-title":"Kidney Int."},{"key":"2024103109403472900_cit8","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1681\/ASN.V132431","article-title":"Aristolochic acids induce chronic renal failure with interstitial fibrosis in salt-depleted rats","volume":"13","author":"Debelle","year":"2002","journal-title":"J. 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Biol. Chem."},{"key":"2024103109403472900_cit15","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/BF00333900","article-title":"On the histopathogenesis of rat forestomach carcinoma caused by aristolochic acid","volume":"52","author":"Mengs","year":"1983","journal-title":"Arch. Toxicol."},{"key":"2024103109403472900_cit16","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1007\/BF00295084","article-title":"Acute toxicity of aristolochic acid in rodents","volume":"59","author":"Mengs","year":"1987","journal-title":"Arch. Toxicol."},{"key":"2024103109403472900_cit17","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/BF01973700","article-title":"Renal toxicity of aristolochic acid in rats as an example of nephrotoxicity testing in routine toxicology","volume":"67","author":"Mengs","year":"1993","journal-title":"Arch. 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