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.
Seidman
M D
MD
Department of Otolaryngology-Head and Neck Surgery, Henry Ford Hospital, Detroit, MI 48202.
Quirk
W S
WS
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003051:Cochlea / Q000098:blood supply* / Q000503:physiopathology; D003055:Cochlear Microphonic Potentials / Q000187:drug effects; D005609:Free Radicals; D007511:Ischemia / Q000150:complications / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors*; D011281:Pregnatrienes / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*
D005609:Free Radicals; D008054:Lipid Peroxides; D011281:Pregnatrienes; C053355:tirilazad