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Hypothesis: Erythropoietin (EPO) may protect against cisplatin-induced ototoxicity in HEI-OC1 auditory cell line., Background: Cisplatin is a widely used chemotherapeutic agent for the treatment of human solid tumors limited by its high incidence of ototoxicity. Currently, there are no clinical solutions. EPO has been reported to have varieties of neuroprotective effects. However, nothing has yet been reported on its potential to prevent cisplatin ototoxicity in auditory cell lines and possible mechanism., Methods: HEI-OC1 cells were incubated with 20 μM of cisplatin for 48 hours, after application of various concentrations of EPO for 24 hours. Cell viability was determined using a Cell Counting Kit-8 (CCK-8) assay. Oxidative stress and apoptosis were assessed by reactive oxygen species (ROS) measurement, Hoechst 33258 staining, and flow cytometry (FC). Western blot (WB) and real-time quantitative PCR were used to detect nuclear factor erythroid 2-related factor 2 (Nrf2), NAD (P)H quinone oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), Bcl-2 and Bcl-xl protein and mRNA expression levels., Results: Pretreatment with 40, 8, and 1.6 ng/mL of EPO for 24 hours before application of 20 μM cisplatin increased cell viability in HEI-OC1 cells. Besides, EPO enhanced the expression of Nrf-2, HO-1, and NQO1. Moreover, upregulation of the expression of Bcl-2 and bcl-xl were also observed., Conclusion: Our results suggest that EPO alleviates cisplatin-induced ototoxicity by activating Nrf2-ARE signaling.

Ototoxicity is one of the most important adverse effects of cisplatin chemotherapy. As a common treatment of acute sensorineural hearing loss, systemic administration of steroids was demonstrated ineffective against cisplatin-induced hearing loss (CIHL) in published studies. The current study aimed to evaluate the potential protective effect of dexamethasone (DEX) encapsulated in polyethyleneglycol-coated polylactic acid (PEG-PLA) nanoparticles (DEX-NPs) against cisplatin-induced hearing loss following systemic administration. DEX was fabricated into PEG-PLA nanoparticles using emulsion and evaporation technique as previously reported. DEX or DEX-NPs was administered intraperitoneally to guinea pigs 1h before cisplatin administration. Auditory brainstem response (ABR) threshold shifts were measured at four frequencies (4, 8, 16, and 24kHz) 1 day before and three days after cisplatin injection. Cochlear morphology was examined to evaluate inner ear injury induced by cisplatin exposure. A single dose of DEX-NPs 1h before cisplatin treatment resulted in a significant preservation of the functional and structural properties of the cochlea, which was equivalent to the effect of multidose (3 days) DEX injection. In contrast, no significant protective effect was observed by single dose injection of DEX. The results of histological examination of the cochleae were consistent with the functional measurements. In conclusion, a single dose DEX-NPs significantly attenuated cisplatin ototoxicity in guinea pigs after systemic administration at both histological and functional levels indicating the potential therapeutic benefits of these nanoparticles for enhancing the delivery of DEX in acute sensorineural hearing loss., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Polyethylene glycol (PEG) and pH‐sensitive polymers have been widely utilized in anticancer drug delivery systems due to their characteristics of prolonging circulation time and tumor‐responsive drug release. However, the effect of PEG molecular weight on the delivery of anticancer drug‐encapsulating pH‐sensitive polymer micelles has been poorly studied. Therefore, a simple method was used to prepare pH‐sensitive doxorubicin (DOX)‐loaded micelles (DOX/POD) based on polyethylene glycol‐2‐(octadecyloxy)‐1, 3‐dioxan‐5‐amine (POD) polymers, and the influence of PEG molecular weights (1 K, 2 K, and 5 K) on in vitro drug release and antitumor effect was further studied. Interestingly, as the molecular weight increased, the release amount of DOX was augmented. While the cytotoxicity and cellular uptake were increased, the molecular weight was decreased. It is reasonable to speculate that the high molecular weight of PEG may promote the dissolution rate of DOX, and their micelles with uncompact structure are being prone to disassembly in an acid environment. However, the low molecular weight of PEG may contribute to the formation of compact POD micelles, which make it easier to be uptaken by tumor cells resulting in the enhanced antitumor effect. Taken together, the results indicate that pH‐sensitive POD micelles with low molecular weight can achieve the efficient delivery of drugs, and PEG molecular weight in pH‐sensitive nanocarriers may influence the antitumor effect. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47854. [ABSTRACT FROM AUTHOR]