Ischemia-reperfusion injury of the cochlea: effects of an iron chelator and nitric oxide synthase inhibitors

Release of free iron from cellular stores and activation of nitric oxide sy nthase (NOS) has been implicated in a wide variety of cochlear injuries. In order to evaluate the effects of deferoxamine (a iron chelator), 3-bromo-7 -nitroindazole (a relatively selective neuronal NOS (nNOS) inhibitor) or am inoguanidine (a relatively selective inducible NOS (iNOS) inhibitor) on the post-ischemic cochlear dysfunction, albino guinea pigs were subjected to 3 0 min ischemia, and the threshold shifts of the compound action potential ( CAP) from pre-ischemic values were compared with those of control animals 4 h after the onset of reperfusion. A statistically significant reduction in the post-ischemic CAP threshold shift was observed in the animals treated with deferoxamine or 3-bromo-7-nitroindazole. However, aminoguanidine did n ot affect the post-ischemic CAP threshold shift. These results suggest that free iron and nNOS play deleterious roles in the cochlear injury induced b y transient ischemia. (C) 2001 Elsevier Science B.V. All rights reserved.