screening / dose selection for ototoxicity or otoprotection
in vitro assay on otic cell line
Cilcare’s in vitro screening model allows the study and screening of the otoprotective properties of a large library of drug candidates in a short timeframe.
The assay is performed on the immortalized cell line HEI-OC1 derived from the mouse’s organ of Corti (Kalinec et al., 2003). These cells are taken from early-stage mouse cochleae and express specific markers including those of cochlear sensory cells and supporting cells. Used in more than 250 studies, HEI-OC1 is a reference cell line in inner ear research. They represent a valuable tool for screening since the auditory system has an extremely complex anatomy, is relatively small, and encased in several layers of bone.
Otoprotection with NAC
CILcare’s model demonstrated the ability of N-Acetyl Cystein (NAC) to protect from cisplatin damage, both with MTT and CCK8 assays.
Characterization with NAC
CILcare’s model allowed to emphasize NAC’s mechanism of action in cisplatin-induced ototoxicity: NAC partially prevented caspase activation in a dose-dependent fashion and completely abrogated the ROS production.
CILcare’s in vitro model is also a valuable and reliable assay to identify potential ototoxic compounds at early phase.
Cisplatin ototoxicity in HEI-OC1 cells
Cell metabolism and quantification with cisplatin
A compound’s potential ototoxicity can be assessed in comparison to cisplatin or any other reference ototoxic drug. Additional assays for apoptosis, with annexin, caspase 3-7 and -8 activities, and for ROS production can also be performed to provide insight into the mechanism of action of drug candidates.
A variety of complementary read outs for otoprotection and ototoxicity screenings
- ROS production
- Apoptosis vs Necrosis
- Caspase 3/7 activation
- Caspase 8 activation
- Intracellular Ca++ increase
- Mitochondrial functionality
- Morphological alterations
- Cytokine production
- Transcriptomics analysis
This in vitro screening model is offered in partnership with Neuro-Zone.