2024-03-28T11:59:01Z
https://nagoya.repo.nii.ac.jp/oai
oai:nagoya.repo.nii.ac.jp:00028483
2023-01-16T04:21:03Z
499:500:501
Acute kidney injury model established by systemic glutathione depletion in mice
Matsubara, Akiko
93365
Oda, Shingo
93366
Jia, Ru
93367
Yokoi, Tsuyoshi
93368
acute kidney injury
animal model
BSO
glutathione
myoglobin
Glutathione (GSH) is one of the most extensively studied tripeptides. The roles for GSH in redox signaling, detoxification of xenobiotics and antioxidant defense have been investigated. A drug‐induced rhabdomyolysis mouse model was recently established in L‐buthionine‐(S,R)‐sulfoximine (BSO; a GSH synthesis inhibitor)‐treated normal mice by co‐administration of antibacterial drug and statin. In these models, mild kidney injury was observed in the BSO only‐treated mice. Therefore, in this study, we studied kidney injury in the GSH‐depleted mouse. BSO was intraperitoneally administered twice a day for 7 days to normal mice. The maximum level of plasma creatine phosphokinase (351 487 ± 53 815 U/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‐1 and urinary creatinine were observed. An increase of mRNA expression level of renal lipocalin 2/neutrophil gelatinase‐associated lipocalin was observed. Degeneration and necrosis in the skeletal muscle and high concentrations of myoglobin (Mb) in blood (347‐203 925 ng/mL) and urine (2.5‐68 583 ng/mL) with large interindividual variability were shown from day 5 of BSO administration. Mb‐stained regions in the renal tubule and renal cast were histologically observed. In this study, the GSH‐depletion 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‐clinical drug development.
ファイル公開:2020-06-01
journal article
Wiley
2019-06
application/pdf
Journal of Applied Toxicology
6
39
919
930
0260-437X
https://nagoya.repo.nii.ac.jp/record/28483/files/appendPDF.pdf
eng
https://doi.org/10.1002/jat.3780
This is the peer reviewed version of the following article: [Matsubara, A, Oda, S, Jia, R, Yokoi, T. Acute kidney injury model established by systemic glutathione depletion in mice. J Appl Toxicol. 2019; 39: 919– 930. https://doi.org/10.1002/jat.3780], which has been published in final form at [https://doi.org/10.1002/jat.3780]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.