キシ　セイジ   Seiji Kishi   岸　誠司    所属   川崎医科大学  医学部 臨床医学　腎臓・高血圧内科学    職種   特任准教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	The novel preventive effect of a Japanese ethical Kampo extract formulation TJ-90 (Seihaito) against cisplatin-induced nephrotoxicity.
掲載誌名	正式名：Phytomedicine : international journal of phytotherapy and phytopharmacology 略　 称：Phytomedicine ISSNコード：1618095X/09447113
掲載区分	国外
巻・号・頁	103,pp.154213
著者・共著者	Yasumasa Ikeda, Masafumi Funamoto, Seiji Kishi, Masaki Imanishi, Ken-Ichi Aihara, Yoshiki Kashiwada, Koichiro Tsuchiya
発行年月	2022/08
概要	BACKGROUND AND PURPOSE:Chinese herbal medicine has been developed as the traditional Japanese Kampo medicine, and it has been widely used to cure various symptoms in clinical practice. However, only a few studies are currently available on the effect of the Kampo medicine on renal disease. Nephrotoxicity is one of major side effect of cisplatin, the first metal-based anticancer drug. In the present study, we examined the effect of the Kampo medicine against cisplatin-induced nephrotoxicity (CIN).METHODS:First, we screened the ethical Kampo extract formulation having positive effect against CIN using HK-2 cells. Next, we examined the preventive action of the selected ethical Kampo extract formulation against CIN in vivo using a mouse model.RESULTS:Cisplatin-induced cell death was significantly suppressed by TJ-43 (Rikkunshito) and TJ-90 (Seihaito); however, cisplatin-induced cleaved caspase-3 expression was inhibited only by TJ-90. In an in vivo mouse model of cisplatin-induced kidney injury with dysfunction and increased inflammatory cytokine expression, TJ-90 showed amelioration of these damaging effects. Cisplatin-induced apoptosis and superoxide production were inhibited by treatment with TJ-90. The expression of cleaved caspase-3, 4-hydroxynonenal, and MAPK phosphorylation increased after cisplatin administration, but decreased after the administration of TJ-90. Among 16 crude drug extracts present in Seihaito, Bamboo Culm (Chikujo in Japanese) inhibited cisplatin-induced cell death and cleaved caspase-3 expression in HK-2 cells. Moreover, the anti-tumor effect of cisplatin was not affected by TJ-90 co-treatment in cancer cell lines.CONCLUSION:TJ-90 might have a novel preventive action against CIN through the suppression of inflammation, apoptosis, and oxidative stress without interfering with the anti-tumor effect of cisplatin. Collectively, these findings might contribute to innovations in supportive care for cancer treatment-related side effects.
DOI	10.1016/j.phymed.2022.154213
PMID	35671634