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The roles for GSH in redox signaling, detoxification of xenobiotics and antioxidant defense have been investigated. A drug\u2010induced rhabdomyolysis mouse model was recently established in L\u2010buthionine\u2010(<jats:italic>S,R<\/jats:italic>)\u2010sulfoximine (BSO; a GSH synthesis inhibitor)\u2010treated normal mice by co\u2010administration of antibacterial drug and statin. In these models, mild kidney injury was observed in the BSO only\u2010treated mice. Therefore, in this study, we studied kidney injury in the GSH\u2010depleted mouse. BSO was intraperitoneally administered twice a day for 7\u00a0days to normal mice. The maximum level of plasma creatine phosphokinase (351\u00a0487\u00a0\u00b1\u00a053\u00a0815\u00a0U\/L) was shown on day 8, and that of aspartate aminotransferase was shown on day 6. Increased levels of blood urea nitrogen, plasma creatinine, urinary kidney injury molecule\u20101 and urinary creatinine were observed. An increase of mRNA expression level of renal lipocalin 2\/neutrophil gelatinase\u2010associated lipocalin was observed. Degeneration and necrosis in the skeletal muscle and high concentrations of myoglobin (Mb) in blood (347\u2010203\u00a0925\u00a0ng\/mL) and urine (2.5\u201068\u00a0583\u00a0ng\/mL) with large interindividual variability were shown from day 5 of BSO administration. Mb\u2010stained regions in the renal tubule and renal cast were histologically observed. In this study, the GSH\u2010depletion treatment established an acute kidney injury mouse model due to Mb release from the damaged skeletal muscle. This mouse model would be useful for predicting potential acute kidney injury risks in non\u2010clinical drug development.<\/jats:p>","DOI":"10.1002\/jat.3780","type":"journal-article","created":{"date-parts":[[2019,2,15]],"date-time":"2019-02-15T07:55:24Z","timestamp":1550217324000},"page":"919-930","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Acute kidney injury model established by systemic glutathione depletion in mice"],"prefix":"10.1002","volume":"39","author":[{"given":"Akiko","family":"Matsubara","sequence":"first","affiliation":[{"name":"Department of Drug Safety Sciences, Division of Clinical Pharmacology Nagoya University Graduate School of Medicine  65 Tsurumai\u2010cho, Showa\u2010ku Nagoya 466\u20108550 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