Juzentaihoto alleviates cisplatin‐induced renal injury in mice

Author:

Yoshioka Hiroki123ORCID,Tominaga Sarah45,Amano Fumiya1,Wu Sixun6,Torimoto Shintaro1,Moriishi Takeshi6,Tsukiboshi Yosuke15,Yokota Satoshi7,Miura Nobuhiko8,Inagaki Naoki1,Matsushita Yuki6,Maeda Tohru34

Affiliation:

1. Faculty of Pharmacy Gifu University of Medical Science Gifu Japan

2. Department of Hygiene Kitasato University, School of Medicine Sagamihara Japan

3. College of Pharmacy Kinjo Gakuin University Nagoya Japan

4. Graduate School of Pharmaceutical Sciences Kinjo Gakuin University Nagoya Japan

5. Department of Neurotoxicology Nagoya City University Graduate School of Medical Sciences Nagoya Japan

6. Department Cell Biology Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan

7. Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research National Institute of Health Sciences Kawasaki Japan

8. Department of Health Science Yokohama University of Pharmacy Yokohama Japan

Abstract

AbstractAimCisplatin 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.MethodsFour 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.ResultsCisplatin 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.ConclusionOur 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.

Publisher

Wiley

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