The protective effects of tirilated mesylate (U74006F) on ischemic and reperfusion-induced cochlear damage

We have recently demonstrated that allopurinol, a blocker of free oxygen radical (FOR) production, and superoxide dismutase (SOD), a scavenger of FOR, protect the cochlea from damage associated with ischemia/reperfusion. The purpose of this present study was to determine if tirilated mesylate (U74006F), a potent inhibitor of lipid peroxidation, can also protect the cochlea from ischemia/reperfusion. Eleven Wistar-Kyoto rats were randomly assigned to two groups: (1) a control group (6 animals) that was exposed to 15 minutes of cochlear ischemia by clamping the anterior-inferior cerebellar artery (AICA), followed by 15 minutes of reperfusion, and (2) a drug-treated group (5 animals) that received U74006F before ischemia/reperfusion. In the control group, the tone burst-evoked compound action potential (CAP) recorded from the round window (RW) was abolished and cochlear microphonic (CM) was reduced. In contrast, the U74006F-treated animals showed post-reperfusion sensitivity in CAP, and less of a CM threshold shift. We interpret these results to indicate that U74006F lessens cochlear damage occurring as a result of ischemia/reperfusion and supports the hypothesis that FOR-induced lipid peroxidation may be partly responsible for the cochlear damage that occurs from ischemia.