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KMID : 0379520180340020133
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한국독성학회지
2018 Volume.34 No. 2 p.133 ~ p.141
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Beneficial Effects of Cynaroside on Cisplatin-Induced Kidney Injury In Vitro and In Vivo
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Nho Jong-Hyun
Jung Hee-Jae
Lee Mu-Jin
Jang Ji-Hun
Sim Mi-Ok
Jeong Da-Eun
Cho Hyun-Woo
Kim Jong-Choon
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Abstract
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Anti-cancer drugs such as cisplatin and doxorubicin are effectively used more than radiotherapy. Cisplatin is a chemotherapeutic drug, used for treatment of various forms of cancer. However, it has side effects such as ototoxicity and nephrotoxicity. Cisplatin-induced nephrotoxicity increases tubular damage and renal dysfunction. Consequently, we investigated the beneficial effect of cynaroside on cisplatin-induced kidney injury using HK-2 cell (human proximal tubule cell line) and an animal model. Results indicated that 10 μM cynaroside diminished cisplatin- induced apoptosis, mitochondrial dysfunction and caspase-3 activation, cisplatin-induced upregulation of caspase-3/MST-1 pathway decreased by treatment of cynaroside in HK-2 cells. To confirm the effect of cynaroside on cisplatin-induced kidney injury in vivo, we used cisplatin exposure animal model (20 mg/kg, balb/c mice, i.p., once a day for 3 days). Renal dysfunction, tubular damage and neutrophilia induced by cisplatin injection were decreased by cynaroside (10 mg/kg, i.p., once a day for 3 days). Results indicated that cynaroside decreased cisplatin-induced kidney injury in vitro and in vivo, and it could be used for improving cisplatin-induced side effects. However, further experiments are required regarding toxicity by high dose cynaroside and caspase-3/MST-1-linked signal transduction in the animal model.
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KEYWORD
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Cisplatin, Cynaroside, HK-2, Nephrotoxicity, MST-1
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