Preventive Effect of TJ-90 against cisplatin-induced nephrotoxicity
Ikeda, Yasumasa Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Funamoto, Masafumi Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Kishi, Seiji Kawasaki Medical School KAKEN Search Researchers
Imanishi, Masaki Tokushima University Tokushima University Educator and Researcher Directory
Aihara, Ken-ichi Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Kashiwada, Yoshiki Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
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.
© 2022. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
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