Evaluation of the Bilirubin Ototoxicity using ABR and DPOAE in Jaundiced Gunn Rats / 대한이비인후과학회지

ABSTRACT

BACKGROUND AND OBJECTIVES: In neonatal hyperbilirubinemia, accumulation of unconjugated bilirubin in the central auditory pathway and basal ganglia may cause sensorineural hearing loss and neurologic sequelae. The effect of unconjugated bilirubin on the brain is known well through auditory brainstem responses (ABRs). However, there is no evidence of pathologic changes in the cochlea. Jaundiced (jj) Gunn rats have been used as a good animal model for hyperbilirubinemia-related auditory dysfunction. The purpose of this study is to evaluate the bilirubin ototoxicity using ABR and DPOAE in jaundiced Gunn rats before and after sulfadimethoxine injection. MATERIALS AND METHOD: Experiments were conducted on three homozygous (jj) P19 (postnatal 19 days) littermates, one heterozygous Gunn rat, five P21 jj littermates, and one nj Gunn rat littermate. P21 jj and nj Gunn rats were re-tested in three weeks in the same condition. ABR with 100-microsecond pulse width click and DPOAEs at 8 kHz, 16 kHz and 22 kHz were measured before and after 1 mg/kg sulfadimethoxine injection. RESULTS: The thresholds of ABR were elevated in P19 and P21 group within the first day after injection and became normalized at several days after injection. Delay of wave II, III, IV and V were also observed. DPOAE showed no significant change after injection in all groups, meaning that the cochlea was not damaged. CONCLUSION: This study shows that bilirubin ototoxicity is related with pathologic changes at or higher than the brainstem level with intact cochlear function. Changes in ABR findings were only observed in P19 and P21 groups because they had higher bilirubin level in blood and their central auditory pathway is more immature than that found in the P42 group. In this study, we also found the possibility of spontaneous recovery from hyperbilirubinemia-related auditory toxicity.