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Platycodin D suppresses cisplatin‐induced cytotoxicity by suppressing ROS‐mediated oxidative damage, apoptosis, and inflammation in HEK‐293 cells
Author(s) -
Hu Junnan,
Leng Jing,
Shen Qiong,
Liu Ying,
Li Xindian,
Wang Shihan,
Li Huiping,
Wang Zi,
Wang Yingping,
Li Wei
Publication year - 2021
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.22624
Subject(s) - oxidative stress , chemistry , reactive oxygen species , cisplatin , apoptosis , superoxide dismutase , pharmacology , nephrotoxicity , malondialdehyde , p38 mitogen activated protein kinases , cytotoxicity , mapk/erk pathway , biochemistry , signal transduction , medicine , toxicity , chemotherapy , in vitro , organic chemistry
Cisplatin, a proven effective chemotherapeutic agent, has been used clinically to treat malignant solid tumors, whereas its clinical use is limited by serious side effect including nephrotoxicity. Platycodin D (PD), the major and marked saponin isolated from Platycodon grandiflorum , possesses many pharmacological effects. In this study, we evaluated its protective effect against cisplatin‐induced human embryonic kidney 293 (HEK‐293) cells injury and elucidated the related mechanisms. Our results showed that PD (0.25, 0.5, and 1 μM) can dose‐dependently alleviate oxidative stress by decreasing malondialdehyde and reactive oxygen species, while increasing the levels of glutathione, superoxide dismutase, and catalase. Moreover, the elevation of apoptosis including Bax, Bad, cleaved caspase‐3,‐9, and decreased protein levels of Bcl‐2, Bcl‐XL induced by cisplatin were reversed after PD treatment. Importantly, PD pretreatment can also regulate PI3K/Akt and ERK/JNK/p38 signaling pathways. Furthermore, PD was found to reduce NF‐κB‐mediated inflammatory relative proteins. Our finding indicated that PD exerted significant effects on cisplatin induced oxidative stress, apoptosis and inflammatory, which will provide evidence for the development of PD to attenuate cisplatin‐induced nephrotoxicity.