Juzentaihoto alleviates cisplatin‐induced renal injury in mice

Hiroki Yoshioka, S. Tominaga, Fumiya Amano, Sixun Wu, Shintaro Torimoto, Takeshi Moriishi, Yosuke Tsukiboshi, Satoshi Yokota, Nobuhiko Miura, Naoki Inagaki, Yuki Matsushita, Tohru Maeda
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Abstract

Cisplatin is a highly effective anti‐cancer agent, but its clinical use is restricted due to severe renal toxicity. This study aimed to investigate the alleviative effects of juzentaihoto (JTT) in a mouse model of cisplatin‐induced renal injury.Four groups of seven‐week‐old male C57BL/6J mice (control, JTT, cisplatin, and JTT + cisplatin groups) were used in the study. The JTT and JTT + cisplatin groups received oral JTT (500 mg/kg) once a day for three days. After 24 h, the cisplatin, and JTT + cisplatin groups were intraperitoneally injected with cisplatin (15 mg/kg). The mice in each group were euthanized 72 h after cisplatin administration, and blood and kidney samples were collected.Cisplatin injection decreased body weight and elevated plasma blood urea nitrogen and creatinine levels, while also increasing renal oxidative stress, inflammation, and cell death. These changes were alleviated by JTT administration. We also found that platinum accumulation in the kidneys following cisplatin injection was attenuated by JTT treatment. Furthermore, Mate1 expression levels (a cisplatin efflux transporter) were upregulated by JTT injection.Our results demonstrated that JTT mitigated cisplatin‐induced renal injury in mice by alleviating oxidative stress, inflammation, and cell death, achieved through the upregulation of the cisplatin efflux transporter Mate1.
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九仙台本能减轻顺铂引起的小鼠肾损伤
顺铂是一种高效抗癌药物,但由于其严重的肾毒性,其临床应用受到限制。本研究旨在探讨顺铂诱导的肾损伤小鼠模型中久治本(JTT)的缓解作用。研究使用了四组七周大的雄性 C57BL/6J 小鼠(对照组、JTT 组、顺铂组和 JTT + 顺铂组)。JTT 组和 JTT + 顺铂组每天口服一次 JTT(500 毫克/千克),连续三天。24 小时后,顺铂组和 JTT + 顺铂组腹腔注射顺铂(15 毫克/千克)。注射顺铂后,小鼠体重下降,血浆尿素氮和肌酐水平升高,同时肾脏氧化应激、炎症和细胞死亡增加。服用 JTT 可缓解这些变化。我们还发现,顺铂注射后铂在肾脏的蓄积在 JTT 治疗后有所减轻。我们的研究结果表明,JTT 通过上调顺铂外排转运体 Mate1 的表达水平,缓解了氧化应激、炎症和细胞死亡,从而减轻了顺铂诱导的小鼠肾损伤。
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