Protective effect of ethosuximide on hearing in NOD/LtJ mice via blockage of endogenous apoptosis

Purpose: To determine the protective effect of ethosuximide on the hearing of NOD/LtJ mice, and the underlying mechanism of action. Methods: The mice were randomly assigned to control and treatment groups (20 mice per group). Mice in the treatment group were administered ethosuximide intraperitoneally at a dose of 200mg/kg body weight (bwt), while those in the control group received an equivalent dose of saline via the same route. Both groups were subjected to auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) tests, as well as determination of mRNA expressions of alpha 1G, alpha 1H, alpha 1I, m-calpain, mu-calpain, and caspase-3. Results: At ages of 6 and 9 weeks, ABR values were significantly lower in the treatment group than those in the control group (p < 0.05). At age 3, 6 and 9 weeks, control group DPOAE values were much lower than those in the treatment group. However, at signal frequency of 35344 Hz, DPOAE value was significantly reduced in the treatment group (p < 0.05). There was significant down-regulation in mRNA expressions of alpha 1G, alpha 1H, all, m-calpain, mu-calpain and caspase-3, in the treatment group, when compared with the control group (p < 0.05). Conclusion: Ethosuximide delays mice hearing loss and protects their hearing via a mechanism involving blockage of endogenous apoptotic pathways. This mechanism may provide guidance in the search for suitable new drugs.