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Panax�notoginseng Saponins protect auditory cells against cisplatin‑induced ototoxicity by inducing the AKT/Nrf2 signaling‑mediated redox pathway
- Source :
- Molecular Medicine Reports.
- Publication Year :
- 2020
- Publisher :
- Spandidos Publications, 2020.
-
Abstract
- Cisplatin‑induced cytotoxicity, such as nephrotoxicity, neurotoxicity and ototoxicity, restricts the clinical application of this compound. Panax notoginseng Saponins (PNS) exhibit potent free radical scavenging and antioxidant activity. PNS have been demonstrated to reduce cisplatin‑induced nephrotoxicity and neurotoxicity. The present study investigated the ability of PNS to protect the auditory HEI‑OC1 cell line against ototoxicity induced by cisplatin. PNS induced activation of the AKT/nuclear factor erythroid 2‑related factor 2 (Nrf2) signaling pathway. Following pretreatment with PNS, HEI‑OC1 cells were treated with cisplatin and cultured for 24 h. The viability of HEI‑OC1 cells was examined using a Cell Counting Kit‑8 assay. Double staining analysis was used to measure cell apoptosis. The ability of PNS to reduce reactive oxygen species (ROS) levels was assessed by flow cytometry. The levels of phosphorylated (p)‑AKT, heme oxygenase 1 (HO‑1), NAD(P)H quinone dehydrogenase 1 (NQO1), glutamate‑cysteine ligase catalytic (GCLC) and Nrf2 were measured by western blotting. HEI‑OC1 cells that were pretreated with PNS exhibited significantly increased cell viability compared with that noted in cells treated only with cisplatin. In addition, PNS suppressed the induction of apoptosis and ROS production following cisplatin treatment. The upregulation of NQO1, HO‑1 and GCLC expression in PNS‑pretreated cells was associated with p‑AKT levels and the activation of Nrf2. These findings suggested that PNS protected auditory cells against ototoxicity induced by cisplatin by activating AKT/Nrf2 signaling. PNS may serve as a potential candidate in regulating cisplatin‑induced cytotoxicity.
- Subjects :
- Male
0301 basic medicine
Cancer Research
Cell Survival
NF-E2-Related Factor 2
Panax notoginseng
Pharmacology
Models, Biological
Biochemistry
Cell Line
Mice
03 medical and health sciences
0302 clinical medicine
Ototoxicity
Hair Cells, Auditory
Genetics
medicine
Animals
Viability assay
Phosphorylation
Molecular Biology
Protein kinase B
chemistry.chemical_classification
Cisplatin
Reactive oxygen species
Chemistry
Saponins
medicine.disease
Heme oxygenase
Oxidative Stress
030104 developmental biology
GCLC
Gene Expression Regulation
Oncology
Apoptosis
030220 oncology & carcinogenesis
Molecular Medicine
Proto-Oncogene Proteins c-akt
Signal Transduction
medicine.drug
Subjects
Details
- ISSN :
- 17913004 and 17912997
- Database :
- OpenAIRE
- Journal :
- Molecular Medicine Reports
- Accession number :
- edsair.doi.dedup.....a6a674703cdef16193592af522229470