The effects of leupeptin on cochlear blood flow, auditory sensitivity, and histology

The purpose of this study was to evaluate the long-term safety of administering leupeptin (1 mg/ml in Hank's Balanced Salt Solution) to the round window membrane by investigating its effects on cochlear blood flow, auditory sensitivity (i.e., auditory brainstem response), and cochlear histology. A comparison of baseline and posttreatment measurements of cochlear blood flow and mean arterial blood pressure in guinea pigs revealed no significant changes. Auditory brainstem response measurements revealed no significant changes in auditory threshold shifts when compared to controls at the 2-, 4-, 6-, and 8-week time points. Furthermore, poststudy surface preparations of the organs of Corti and cytocochleograms from leupeptin-treated ears and controls revealed no significant hair cell losses. These data suggest that the prolonged administration of leupeptin (1 mg/ml at a rate of 0.5 microliter/hr for 8 weeks) to the round window membrane is not ototoxic. This study may serve as a basis for future clinical trials of leupeptin administration for the prevention or treatment of noise-induced hearing loss and the management of tinnitus.