ABSTRACT
Astaxanthine (AST) has important biological activities including antioxidant and anti-inflammatory effects that could alleviate neurological and heart diseases, but its role in the prevention of cisplatin-induced hearing loss (CIHL) is not yet well understood. In our study, a steady interaction between AST and the E3 ligase adapter Kelch-like ECH-associated protein 1, a predominant repressor of nuclear factor erythroid 2-related factor 2 (NRF2), was performed and tested via computer molecular docking and dynamics. AST protected against cisplatin-induced ototoxicity via NRF2 mediated pathway using quantitative PCR and Western blotting. The levels of reactive oxygen species (ROS) and mitochondrial membrane potential revealed that AST reduced ROS overexpression and mitochondrial dysfunction. Moreover, AST exerted anti-apoptosis effects in mouse cochlear explants using immunofluorescence staining and HEI-OC1 cell lines using quantitative PCR and Western blotting. Finally, AST combined with poloxamer was injected into the middle ear through the tympanum, and the protection against CIHL was evaluated using the acoustic brain stem test and immunofluorescent staining in adult mice. Our results suggest that AST reduced ROS overexpression, mitochondrial dysfunction, and apoptosis via NRF2-mediated pathway in cisplatin-exposed HEI-OC1 cell lines and mouse cochlear explants, finally promoting cell survival. Our study demonstrates that AST is a candidate therapeutic agent for CIHL.
ABSTRACT
Objective@#Acoustic pharyngealmetry technology is utilized to evaluate the change and clinical significance of obstructive sleep apnea-hypopnea syndrome (OSAHS) patients caused by non-upper airway structural factor and normal individuals′ PWF(pharyngeal wall floppiness).@*Methods@#Acoustic pharyngealmetry instrument of Ecconvision was utilized to examine 102 OSAHS patients and 50 normal individuals, separately recorded their volume of pharyngeal cavity in sit or supine position, calculated PWF in sit or supine position, and SPSS 12.0 of tware was used to analyze data.@*Results@#PWF was 0.14±0.09 in sit position and PWF was 0.21±0.10, (t=5.96, t=9.63, P<0.001)in supine position of OSAHS group, which were all significantly higher than those of control group. PWFs in supine position of OSAHS group and control group were evidently higher than PWF(t=-11.91, P<0.001; t=-2.32, P=0.025) in sit position. ΔPWF(PWF_supine-PWF_sit)was 0.063±0.054 in OSAHS group which was significantly greater than in control(F=41.173, P<0.01). PWF in sit position and supine position were all positively related with age(r=0.714, r=0.735, P<0.001)while irrelevant with BMI(P>0.05).@*Conclusions@#PWF can be utilized to be an index to reflect the physiological feature of upper airway. PWF can more precisely reflect upper airway collapsibility of OSAHS patients on the condition of PWF in supine position. Pharyngeal wall floppiness quantified as a high PWF index is a non-structure vital factor of OSAHS patients and plays a role of guiding us to make personal treatment plans for OSAHS patients.