| ○種別 (必須): | □ | 学術論文 (審査論文)
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| ○言語 (必須): | □ | 英語
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| ○著者 (必須): | 1. | (英) Iwamura Atsushi (日) (読)
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| 2. | (英) Watanabe Katsuhito (日) (読)
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| 3. | (英) Akai Sho (日) (読)
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| 4. | (英) Nishinosono Tsubasa (日) (読)
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| 5. | 常山 幸一 ([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.病理系.疾患病理学])
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| 6. | (英) Oda Shingo (日) (読)
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| 7. | (英) Kume Toshiyuki (日) (読)
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| 8. | (英) Yokoi Tsuyoshi (日) (読)
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| ○題名 (必須): | □ | (英) Zomepirac Acyl Glucuronide Is Responsible for Zomepirac-Induced Acute Kidney Injury in Mice. (日)
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| ○要約 (任意): | □ | (英) Glucuronidation, an important phase II metabolic route, is generally considered to be a detoxification pathway. However, acyl glucuronides (AGs) have been implicated in the toxicity of carboxylic acid drugs due to their electrophilic reactivity. Zomepirac (ZP) was withdrawn from the market because of adverse effects such as renal toxicity. Although ZP is mainly metabolized to acyl glucuronide (ZP-AG) by UDP-glucuronosyltransferase, the role of ZP-AG in renal toxicity is unknown. In this study, we established a ZP-induced kidney injury mouse model by pretreatment with tri-o-tolyl phosphate (TOTP), a nonselective esterase inhibitor, and l-buthionine-(S,R)-sulfoximine (BSO), a glutathione synthesis inhibitor. The role of ZP-AG in renal toxicity was investigated using this model. The model showed significant increases in blood urea nitrogen (BUN) and creatinine (CRE), but not alanine aminotransferase. The ZP-AG concentrations were elevated by cotreatment with TOTP in the plasma and liver and especially in the kidney. The ZP-AG concentrations in the kidney correlated with values for BUN and CRE. Upon histopathological examination, vacuoles and infiltration of mononuclear cells were observed in the model mouse. In addition to immune-related responses, oxidative stress markers, such as the glutathione/disulfide glutathione ratio and malondialdehyde levels, were different in the mouse model. The suppression of ZP-induced kidney injury by tempol, an antioxidant agent, suggested the involvement of oxidative stress in ZP-induced kidney injury. This is the first study to demonstrate that AG accumulation in the kidney by TOTP and BSO treatment could explain renal toxicity and to show the in vivo toxicological potential of AGs. (日)
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| ○誌名 (必須): | □ | Drug Metabolism and Disposition (American Society for Pharmacology and Experimental Therapeutics)
(pISSN: 0090-9556, eISSN: 1521-009X)
| ○ISSN (任意): | □ | 1521-009X
ISSN: 0090-9556
(pISSN: 0090-9556, eISSN: 1521-009X) Title: Drug metabolism and disposition: the biological fate of chemicalsTitle(ISO): Drug Metab DisposPublisher: American Society for Pharmacology and Experimental Therapeutics (NLM Catalog)
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| ○巻 (必須): | □ | 44
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| ○号 (必須): | □ | 7
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| ○頁 (必須): | □ | 888 896
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| ○年月日 (必須): | □ | 西暦 2016年 4月 25日 (平成 28年 4月 25日)
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| ○URL (任意): |
| ○DOI (任意): | □ | 10.1124/dmd.116.069575 (→Scopusで検索)
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| ○PMID (任意): | □ | 27112166 (→Scopusで検索)
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| ○備考 (任意): | 1. | (英) Article.ELocationID: 10.1124/dmd.116.069575 (日)
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| 2. | (英) Article.PublicationTypeList.PublicationType: Journal Article (日)
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