Increased Excretion of Urinary 20-HETE in Rats With Cyclosporine-Induced Nephrotoxicity
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- Seki Takayuki
- Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd.
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- Ishimoto Tsuyoshi
- Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd.
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- Sakurai Takanobu
- Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd.
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- Yasuda Yoshiko
- Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd.
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- Taniguchi Kazuo
- Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd.
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- Doi Mariko
- Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd.
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- Sato Mariko
- Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd.
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- Roman Richard J.
- Department of Physiology, Medical College of Wisconsin
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- Miyata Noriyuki
- Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd.
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抄録
The present study examined the contribution of 20-hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE) in cyclosporine A (CsA)-induced renal nephrotoxicity. Treatment of rats with CsA (50 mg/kg) for 9 days induced renal damage as indicated by marked increase in urine flow (from 9.0 ± 0.3 ml/day to 46.6 ± 7.1 ml/day) and a 3 – 5-fold rise in blood urea nitrogen (BUN) levels. The urinary excretion of 20-HETE increased from 164 ± 5 ng/day (N = 5) to 2432 ± 290 ng/day (N = 5, P<0.01) after 9 days of CsA treatment. The increase in the urinary excretion of 20-HETE in the CsA treated rats was highly correlated with the increase in BUN levels (r = 0.819, P<0.001) and urine volume (r = 0.832, P<0.001). Immunohistochemical examination of kidney revealed that expression of cytochrome P450 4A (CYP4A) protein was markedly enhanced in the proximal tubules of CsA-treated rats. These results indicate that CsA-induced nephrotoxicity in rats is associated with a marked elevation in the renal production of 20-HETE and that 20-HETE may contribute to the pathophysiological condition of CsA-induced nephrotoxicity.<br>
収録刊行物
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- Journal of Pharmacological Sciences
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Journal of Pharmacological Sciences 97 (1), 132-137, 2005
公益社団法人 日本薬理学会
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詳細情報 詳細情報について
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- CRID
- 1390001205176181504
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- NII論文ID
- 10025725562
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- NII書誌ID
- AA11806667
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- ISSN
- 13478648
- 13478613
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- NDL書誌ID
- 7228675
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- PubMed
- 15655287
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 使用不可