Acute nephrotoxicity of aristolochic acids in mice

Noriko Sato, Daisuke Takahashi, Shih Ming Chen, Reiko Tsuchiya, Takuya Mukoyama, Shin Ichi Yamagata, Makoto Ogawa, Masaaki Yoshida, Seizo Kondo, Nobunori Satoh, Shiro Ueda

研究成果: 雜誌貢獻文章

85 引文 (Scopus)

摘要

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 1 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.

原文英語
頁(從 - 到)221-229
頁數9
期刊Journal of Pharmacy and Pharmacology
56
發行號2
DOIs
出版狀態已發佈 - 二月 2004

指紋

Aristolochic Acids
Interstitial Nephritis
Inbred C3H Mouse
Aristolochia
Kidney
Inbred Strains Mice
Blood Urea Nitrogen
Intraperitoneal Injections
Serum
Inbred C57BL Mouse
Oral Administration
Creatinine
Fibrosis
Necrosis
Salts
Sodium
Urine
Wounds and Injuries

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

引用此文

Sato, N., Takahashi, D., Chen, S. M., Tsuchiya, R., Mukoyama, T., Yamagata, S. I., ... Ueda, S. (2004). Acute nephrotoxicity of aristolochic acids in mice. Journal of Pharmacy and Pharmacology, 56(2), 221-229. https://doi.org/10.1211/0022357023051

Acute nephrotoxicity of aristolochic acids in mice. / Sato, Noriko; Takahashi, Daisuke; Chen, Shih Ming; Tsuchiya, Reiko; Mukoyama, Takuya; Yamagata, Shin Ichi; Ogawa, Makoto; Yoshida, Masaaki; Kondo, Seizo; Satoh, Nobunori; Ueda, Shiro.

於: Journal of Pharmacy and Pharmacology, 卷 56, 編號 2, 02.2004, p. 221-229.

研究成果: 雜誌貢獻文章

Sato, N, Takahashi, D, Chen, SM, Tsuchiya, R, Mukoyama, T, Yamagata, SI, Ogawa, M, Yoshida, M, Kondo, S, Satoh, N & Ueda, S 2004, 'Acute nephrotoxicity of aristolochic acids in mice', Journal of Pharmacy and Pharmacology, 卷 56, 編號 2, 頁 221-229. https://doi.org/10.1211/0022357023051
Sato N, Takahashi D, Chen SM, Tsuchiya R, Mukoyama T, Yamagata SI 等. Acute nephrotoxicity of aristolochic acids in mice. Journal of Pharmacy and Pharmacology. 2004 2月;56(2):221-229. https://doi.org/10.1211/0022357023051
Sato, Noriko ; Takahashi, Daisuke ; Chen, Shih Ming ; Tsuchiya, Reiko ; Mukoyama, Takuya ; Yamagata, Shin Ichi ; Ogawa, Makoto ; Yoshida, Masaaki ; Kondo, Seizo ; Satoh, Nobunori ; Ueda, Shiro. / Acute nephrotoxicity of aristolochic acids in mice. 於: Journal of Pharmacy and Pharmacology. 2004 ; 卷 56, 編號 2. 頁 221-229.
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abstract = "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 1 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.",
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AU - Tsuchiya, Reiko

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AU - Yamagata, Shin Ichi

AU - Ogawa, Makoto

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AU - Ueda, Shiro

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