Horseradish peroxidase ototoxicity

Abstract

Following intracochlear perfusion of horseradish peroxidase (HRP) in artifical perilymph (1% for 10 min–4 h; 1–24 survival), HRP was demonstrated histochemically in some hair cells and supporting cells, the basilar membrane, spiral limbus and stria vascularis of 18 anesthetized (DIAL) guinea pigs. No neuronal retrograde transport occurred. To test for possible HRP ototoxicity, cochlear microphonics (CM) were recorded during presentation of two pure tones (4 kHz, 500 Hz) in four HRP experiments and two controls perfused with artificial perilymph alone. Only six drops of perfusate were used in one HRP and one control animal. No significant variation in CM occurred during perfusion. At stop-flow, CM declined slightly but soon stabilized in both 6-drop animals; decline was greater upon stop flow of either perfusate at one hour, but was greatest after HRP. An animal was then perfused with 10% HRP for one hour; CM declined during perfusion and continued downward at stop flow. Our results indicate ototoxicity of HRP, especially when concentrated, perhaps due to an adverse effect on inner ear fluid balance. Studies which utilized HRP as a tracer in the cochlea should be reassessed.