Comparison of the nephroprotective effects of non-steroidal anti-inflammatory drugs on cisplatin-induced nephrotoxicity in vitro and in vivo

Okamoto, Keisuke; Saito, Yoshitaka; Narumi, Katsuya; Furugen, Ayako; Iseki, Ken; Kobayashi, Masaki

Comparison of the nephroprotective effects of non-steroidal anti-inflammatory drugs on cisplatin-induced nephrotoxicity in vitro and in vivo

Okamoto, Keisuke; Saito, Yoshitaka; Narumi, Katsuya et al.

European journal of pharmacology, 2020, 884, 173339

Permalink : https://hdl.handle.net/2115/82868

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アクセス権	open access
URI	https://hdl.handle.net/2115/82868
タイトル	Comparison of the nephroprotective effects of non-steroidal anti-inflammatory drugs on cisplatin-induced nephrotoxicity in vitro and in vivo
著者	Okamoto, Keisuke ; Saito, Yoshitaka ; Narumi, Katsuya ; Furugen, Ayako ; Iseki, Ken ; Kobayashi, Masaki
著者名 Okamoto, Keisuke
著者名 Saito, Yoshitaka
e-Rad_Researcher 90746752 著者名 Narumi, Katsuya
e-Rad_Researcher 90767261 著者名 Furugen, Ayako
e-Rad_Researcher 40203062 著者名 Iseki, Ken
e-Rad_Researcher 70431319 著者名 Kobayashi, Masaki
言語	英語
キーワード	Cisplatin
	Nephrotoxicity
	NSAIDs
	Celecoxib
発行日	2020-10-05
出版者	Elsevier
収録物名	European journal of pharmacology
巻(号)	884
ページ	173339
抄録	Cisplatin (CDDP) is an anticancer drug, often used in the treatment of several types of cancers. CDDP-induced nephrotoxicity (CIN) is one of the most severe adverse events associated with the use of CDDP. It has been suggested that the co-administration of non-steroidal anti-inflammatory drugs (NSAIDs) is a risk factor for CIN. However, the specific NSAIDs that affect CIN and the precise mechanisms underlying this interaction remain unclear. Hence, we aimed to evaluate the effect of NSAIDs on CDDP-induced cytotoxicity in vitro and confirmed the results in vivo. Using the epithelioid clone of the normal rat kidney cells (NRK-52E cells), we assessed the effects of 17 NSAIDs on CDDP-induced cytotoxicity all at once using the MTT assay. Furthermore, we evaluated two NSAIDs, which significantly attenuated or enhanced CDDP-induced cytotoxicity, in vivo. Wistar rats were treated with CDDP (5 mg/kg, i.p., day 1) and NSAIDs (p.o., day 1-4), and the kidneys were excised on day 5. Our results demonstrated that several NSAIDs attenuated, while others enhanced CDDP-induced cytotoxicity. Celecoxib significantly attenuated and flurbiprofen markedly enhanced cell dysfunction by CDDP. These results were reproduced in vivo as celecoxib decreased and flurbiprofen increased the expression of kidney injury molecule 1 (Kim-1) mRNA, a sensitive kidney injury marker, compared to the CDDP group. Moreover, celecoxib increased the antioxidant and autophagy markers quantified by qPCR in vitro and prevented a decrease in body weight induced by CDDP in vivo. In conclusion, we revealed that celecoxib significantly attenuated CIN in vitro and in vivo.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報	©2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
PISSN	0014-2999
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.ejphar.2020.173339