Damage and threshold shift resulting from cochlear exposure to paraquat-generated superoxide

Abstract

Superoxide has been implicated as a contributing factor to cochlear pathology from a number of sources, including noise and ototoxic drugs. The effects of NADPH oxidase-dependent superoxide on the cochlea were investigated in the current study using paraquat (PQ). PQ is a toxic herbicide that causes tissue damage by generating superoxide through reduction of molecular oxygen in a reaction catalyzed by NADPH oxidase. The current study examined the effects of round window PQ administration on inferior colliculus (IC) evoked potential thresholds (EVP) and hair cell damage. Using implanted IC electrodes, chinchillas were tested for IC EVP thresholds before and after PQ exposure. Ears were exposed to PQ at one of four concentrations: 10, 5, 3 mM, and vehicle control. Thresholds were increased in a dose-dependent manner, and peaked between one and seven days post-exposure. Thresholds then showed a small amount of recovery before reaching PTS by Day 22. Outer and inner hair cell losses were consistent with PTS. The similarities between PQ ototoxicity and noise-induced hearing loss suggest the possibility of similar biochemical pathways involving superoxide.

Fig. 1

Recovery patterns of the 10 mM concentration group for the five frequencies tested, plotted as threshold shift in dB against the Day of testing post-exposure. Error bars are +1 standard deviation.

Fig. 2

Recovery patterns of the 5 mM concentration group for the five frequencies tested, plotted as threshold shift in dB against the Day of testing post-exposure. Error bars are +1 standard deviation.

Fig. 3

Recovery patterns of the 3 mM concentration group for the five frequencies tested, plotted as threshold shift in dB against the Day of testing post-exposure. Error bars are +1 standard deviation.

Fig. 4

PTS for the four experimental groups plotted as dB PTS across frequency. Error bars are +1 standard deviation.

Fig. 5

Mean OHC loss cochleograms for the four concentration groups, plotted as % OHC lost against % distance from the apex of the cochlea.

Fig. 6

Mean IHC loss cochleograms for the four concentration groups, plotted as % IHC lost against % distance from the apex of the cochlea.