Cisplatin-induced ototoxicity occurs in approximately half of patients treated with cisplatin, and pediatric patients are more likely to be affected than adults. The oxidative stress elicited by cisplatin is a key contributor to the pathogenesis of ototoxicity. Notoginsenoside R1 (NGR1), the main bioactive compound of Panax notoginseng saponins, has antioxidant and antiapoptotic effects. This study investigated the ability of NGR1 to protect against cisplatin-induced damage in auditory HEI-OC1 cells and neonatal murine cochlear explants. The viability of HEI-OC1 cells treated with NGR1 and cisplatin was greater than that of cells treated with cisplatin alone. The results of Western blots and immunostaining for cleaved caspase-3 revealed that the level of cleaved caspase-3 in the cells treated with cisplatin was repressed by NGR1. NGR1 attenuated cisplatin-induced cytotoxicity in HEI-OC1 cells. Intracellular reactive oxygen species (ROS) were detected with a DCFDA assay and immunostaining for 4-HNE. The result revealed that its expression was induced by cisplatin and was significantly reduced by NGR1. Moreover, NGR1 can promote heme oxygenase-1 (HO-1) expression at both the mRNA and protein levels. ZNPPIX, an HO-1 inhibitor, was administered to cisplatin-treated cells to investigate the role of HO-1 in the protective effect of NGR1. The suppression of HO-1 activity by ZNPPIX markedly abolished the protective effect of NGR1 on cisplatin-treated cells. Therefore, NGR1 protects cells from cisplatin-induced damage by activating HO-1 and its antioxidative activity. In cochlear explants, NGR1 protects cochlear hair cells and attenuates cisplatin-induced ototoxicity by inhibiting ROS generation. In the group treated with cisplatin alone, prominent loss of outer hair cells and severe damage to the structure of the stereociliary bundles of inner and outer hair cells were observed. Compared with the group treated with cisplatin alone, less loss of outer hair cells (p = 0.009) and better preservation of the stereociliary bundles of hair cells were observed in the group treated with cisplatin and NGR1. In conclusion, these findings indicate that NGR1 can protect against cisplatin-induced ototoxicity by inducing HO-1 expression and suppressing oxidative stress.
机构:
Dalian Med Univ, Affiliated Hosp 1, Dept Gastroenterol, Dalian 0086116011, Liaoning, Peoples R ChinaDalian Med Univ, Affiliated Hosp 1, Dept Gastroenterol, Dalian 0086116011, Liaoning, Peoples R China
Guo, Shi-Bin
Li, Qing
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Dalian Med Univ, Affiliated Hosp 1, Dept Gastroenterol, Dalian 0086116011, Liaoning, Peoples R China
Dalian Friendship Hosp, Dept Gastroenterol, Dalian 0086116011, Liaoning, Peoples R ChinaDalian Med Univ, Affiliated Hosp 1, Dept Gastroenterol, Dalian 0086116011, Liaoning, Peoples R China
Li, Qing
Duan, Zhi-Jun
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Dalian Med Univ, Affiliated Hosp 1, Dept Gastroenterol, Dalian 0086116011, Liaoning, Peoples R ChinaDalian Med Univ, Affiliated Hosp 1, Dept Gastroenterol, Dalian 0086116011, Liaoning, Peoples R China
Duan, Zhi-Jun
Wang, Qiu-Ming
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Dalian Med Univ, Affiliated Hosp 1, Dept Gastroenterol, Dalian 0086116011, Liaoning, Peoples R ChinaDalian Med Univ, Affiliated Hosp 1, Dept Gastroenterol, Dalian 0086116011, Liaoning, Peoples R China
Wang, Qiu-Ming
Zhou, Qin
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Dalian Med Univ, Dept Pharmacol, Dalian 0086116011, Liaoning, Peoples R ChinaDalian Med Univ, Affiliated Hosp 1, Dept Gastroenterol, Dalian 0086116011, Liaoning, Peoples R China
Zhou, Qin
Sun, Xiao-Yu
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Dalian Med Univ, Affiliated Hosp 1, Dept Gastroenterol, Dalian 0086116011, Liaoning, Peoples R ChinaDalian Med Univ, Affiliated Hosp 1, Dept Gastroenterol, Dalian 0086116011, Liaoning, Peoples R China
机构:
Southwest Med Univ, Affiliated Hosp, Dept Cardiol, Lu Zhou, Peoples R ChinaSouthwest Med Univ, Affiliated Hosp, Dept Cardiol, Lu Zhou, Peoples R China
Luo, Jian
Zhu, Qian
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Southwest Med Univ, Affiliated Hosp, Dept Cardiol, Lu Zhou, Peoples R ChinaSouthwest Med Univ, Affiliated Hosp, Dept Cardiol, Lu Zhou, Peoples R China
Zhu, Qian
Huang, Keming
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Southwest Med Univ, Affiliated Hosp, Dept Cardiol, Lu Zhou, Peoples R ChinaSouthwest Med Univ, Affiliated Hosp, Dept Cardiol, Lu Zhou, Peoples R China
Huang, Keming
Wen, Xue
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Southwest Med Univ, Affiliated Hosp, Dept Lab Med, Lu Zhou, Peoples R ChinaSouthwest Med Univ, Affiliated Hosp, Dept Cardiol, Lu Zhou, Peoples R China
Wen, Xue
Peng, Yongquan
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Southwest Med Univ, Affiliated Hosp, Dept Cardiol, Lu Zhou, Peoples R ChinaSouthwest Med Univ, Affiliated Hosp, Dept Cardiol, Lu Zhou, Peoples R China
Peng, Yongquan
Chen, Gong
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Southwest Med Univ, Affiliated Hosp, Dept Cardiol, Lu Zhou, Peoples R ChinaSouthwest Med Univ, Affiliated Hosp, Dept Cardiol, Lu Zhou, Peoples R China
Chen, Gong
Wei, Gang
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Southwest Med Univ, Affiliated Hosp, Dept Cardiol, Lu Zhou, Peoples R ChinaSouthwest Med Univ, Affiliated Hosp, Dept Cardiol, Lu Zhou, Peoples R China
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Anhui Med Univ, Sch Pharm, Hefei, Peoples R China
Anhui Inst Innovat Drugs, Hefei, Peoples R China
Minist Educ, Key Lab Antiinflammatory & Immune Med, Hefei, Peoples R ChinaAnhui Med Univ, Sch Pharm, Hefei, Peoples R China
Gao, Li
Wu, Wei-Feng
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Anhui Med Univ, Sch Pharm, Hefei, Peoples R China
Anhui Inst Innovat Drugs, Hefei, Peoples R China
Minist Educ, Key Lab Antiinflammatory & Immune Med, Hefei, Peoples R ChinaAnhui Med Univ, Sch Pharm, Hefei, Peoples R China
Wu, Wei-Feng
Dong, Lei
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Emory Univ, Childrens Healthcare Atlanta, Aflac Canc & Blood Disorders Ctr, Sch Med,Dept Pediat,Div Hematol & Oncol, Atlanta, GA USAAnhui Med Univ, Sch Pharm, Hefei, Peoples R China
Dong, Lei
Ren, Gui-Ling
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Anhui Med Univ, Sch Pharm, Hefei, Peoples R China
Anhui Inst Innovat Drugs, Hefei, Peoples R China
Minist Educ, Key Lab Antiinflammatory & Immune Med, Hefei, Peoples R ChinaAnhui Med Univ, Sch Pharm, Hefei, Peoples R China
Ren, Gui-Ling
Li, Hai-Di
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Anhui Med Univ, Sch Pharm, Hefei, Peoples R China
Anhui Inst Innovat Drugs, Hefei, Peoples R China
Minist Educ, Key Lab Antiinflammatory & Immune Med, Hefei, Peoples R ChinaAnhui Med Univ, Sch Pharm, Hefei, Peoples R China
Li, Hai-Di
Yang, Qin
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Anhui Med Univ, Sch Pharm, Hefei, Peoples R China
Anhui Inst Innovat Drugs, Hefei, Peoples R China
Minist Educ, Key Lab Antiinflammatory & Immune Med, Hefei, Peoples R ChinaAnhui Med Univ, Sch Pharm, Hefei, Peoples R China
Yang, Qin
Li, Xiao-Feng
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Anhui Med Univ, Sch Pharm, Hefei, Peoples R China
Anhui Inst Innovat Drugs, Hefei, Peoples R China
Minist Educ, Key Lab Antiinflammatory & Immune Med, Hefei, Peoples R ChinaAnhui Med Univ, Sch Pharm, Hefei, Peoples R China
Li, Xiao-Feng
Xu, Tao
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Anhui Med Univ, Sch Pharm, Hefei, Peoples R China
Anhui Inst Innovat Drugs, Hefei, Peoples R China
Minist Educ, Key Lab Antiinflammatory & Immune Med, Hefei, Peoples R ChinaAnhui Med Univ, Sch Pharm, Hefei, Peoples R China
Xu, Tao
Li, Zeng
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Anhui Med Univ, Sch Pharm, Hefei, Peoples R China
Anhui Inst Innovat Drugs, Hefei, Peoples R ChinaAnhui Med Univ, Sch Pharm, Hefei, Peoples R China
Li, Zeng
Wu, Bao-Ming
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Anhui Med Univ, Sch Pharm, Hefei, Peoples R China
Anhui Inst Innovat Drugs, Hefei, Peoples R China
Minist Educ, Key Lab Antiinflammatory & Immune Med, Hefei, Peoples R ChinaAnhui Med Univ, Sch Pharm, Hefei, Peoples R China
Wu, Bao-Ming
Ma, Tao-Tao
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Anhui Med Univ, Sch Pharm, Hefei, Peoples R China
Anhui Inst Innovat Drugs, Hefei, Peoples R China
Minist Educ, Key Lab Antiinflammatory & Immune Med, Hefei, Peoples R ChinaAnhui Med Univ, Sch Pharm, Hefei, Peoples R China
Ma, Tao-Tao
Huang, Cheng
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Anhui Med Univ, Sch Pharm, Hefei, Peoples R China
Anhui Inst Innovat Drugs, Hefei, Peoples R China
Minist Educ, Key Lab Antiinflammatory & Immune Med, Hefei, Peoples R ChinaAnhui Med Univ, Sch Pharm, Hefei, Peoples R China
Huang, Cheng
Huang, Yan
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Anhui Med Univ, Sch Pharm, Hefei, Peoples R China
Anhui Inst Innovat Drugs, Hefei, Peoples R China
Minist Educ, Key Lab Antiinflammatory & Immune Med, Hefei, Peoples R ChinaAnhui Med Univ, Sch Pharm, Hefei, Peoples R China
Huang, Yan
Zhang, Lei
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Anhui Med Univ, Sch Pharm, Hefei, Peoples R China
Anhui Inst Innovat Drugs, Hefei, Peoples R China
Minist Educ, Key Lab Antiinflammatory & Immune Med, Hefei, Peoples R ChinaAnhui Med Univ, Sch Pharm, Hefei, Peoples R China
Zhang, Lei
Lv, Xiongwen
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Anhui Med Univ, Sch Pharm, Hefei, Peoples R China
Anhui Inst Innovat Drugs, Hefei, Peoples R China
Minist Educ, Key Lab Antiinflammatory & Immune Med, Hefei, Peoples R ChinaAnhui Med Univ, Sch Pharm, Hefei, Peoples R China
Lv, Xiongwen
Li, Jun
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Anhui Med Univ, Sch Pharm, Hefei, Peoples R China
Anhui Inst Innovat Drugs, Hefei, Peoples R China
Minist Educ, Key Lab Antiinflammatory & Immune Med, Hefei, Peoples R ChinaAnhui Med Univ, Sch Pharm, Hefei, Peoples R China
Li, Jun
Meng, Xiao-Ming
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Anhui Med Univ, Sch Pharm, Hefei, Peoples R China
Anhui Inst Innovat Drugs, Hefei, Peoples R China
Minist Educ, Key Lab Antiinflammatory & Immune Med, Hefei, Peoples R ChinaAnhui Med Univ, Sch Pharm, Hefei, Peoples R China