Antioxidant effect of ascorbic acid against cisplatin-induced nephrotoxicity and P-glycoprotein expression in rats

Okamoto, Keisuke; Kitaichi, Fumi; Saito, Yoshitaka; Ueda, Hinata; Narumi, Katsuya; Furugen, Ayako; Kobayashi, Masaki

Antioxidant effect of ascorbic acid against cisplatin-induced nephrotoxicity and P-glycoprotein expression in rats

Okamoto, Keisuke; Kitaichi, Fumi; Saito, Yoshitaka et al.

European journal of pharmacology, 2021, 909, 174395

Permalink : https://hdl.handle.net/2115/87012

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アクセス権	open access
URI	https://hdl.handle.net/2115/87012
タイトル	Antioxidant effect of ascorbic acid against cisplatin-induced nephrotoxicity and P-glycoprotein expression in rats
著者	Okamoto, Keisuke ; Kitaichi, Fumi ; Saito, Yoshitaka ; Ueda, Hinata ; Narumi, Katsuya ; Furugen, Ayako ; Kobayashi, Masaki
著者名 Okamoto, Keisuke
著者名 Kitaichi, Fumi
e-Rad_Researcher 00835001 著者名 Saito, Yoshitaka
著者名 Ueda, Hinata
e-Rad_Researcher 90746752 著者名 Narumi, Katsuya
e-Rad_Researcher 90767261 著者名 Furugen, Ayako
e-Rad_Researcher 70431319 著者名 Kobayashi, Masaki
言語	英語
キーワード	Cisplatin
	Ascorbic acid
	Nephrotoxicity
	P-glycoprotein
	Antioxidant
	Transporter
発行日	2021-10-15
出版者	Elsevier
収録物名	European journal of pharmacology
巻(号)	909
ページ	174395
抄録	Cisplatin (CDDP) is a highly potent anticancer drug that is widely used in the treatment of several cancers. CDDP-induced nephrotoxicity (CIN) is one of the most significant adverse effects, and oxidative stress is thought to be one of the mechanisms underlying CIN. Although there are some studies available on the variability in transporter expression in the kidney after a single CDDP dose, none have reported the change in renal transporter expression after multiple CDDP dose administrations. P-glycoprotein (P-gp), a transporter, is reported to be induced by oxidative stress. Ascorbic acid is a vitamin with antioxidant potential and therefore, may regulate the expression of P-gp transporter and affect CIN. In the present study, our aim was to assess the variability in expression of several renal transporters after multiple CDDP dose administrations and the antioxidant effect of ascorbic acid against transporter expression and CIN. Multiple doses of CDDP affected markers of kidney injury and antioxidants in the kidneys. Also, the expression of P-gp, breast cancer resistance protein, and multidrug resistance-associated protein 4 was upregulated by CDDP. Using a normal kidney cell line, we demonstrated that ascorbic acid attenuated CDDP-induced cytotoxicity due to its high superoxide scavenging ability. CDDP and ascorbic acid were injected into rats once a week for three weeks, and it was observed that co-administration of ascorbic acid attenuated CIN and regulated antioxidant marker. In addition, ascorbic acid reduced P-gp expression, which was upregulated by CDDP. In conclusion, ascorbic acid may attenuate CIN and reverse P-gp-mediated changes in drug pharmacokinetics.
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	©2021. 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.2021.174395