Molecular and clinical implications of loop diuretic ototoxicity

Recent advances in molecular biology have been applied to inner ear research. Loop diuretic ototoxicity has been suggested, but not proven, to share a common mechanism with diuretic effects on renal tubules. The discovery of the molecular nature of the Na-K-2Cl cotransporter in the cochlea provided a better understanding of loop diuretic ototoxicity. In this review, we describe clinical reports of loop diuretic ototoxicity and other information obtained by physiological, biochemical and morphological investigations related to the mechanism sensitive to loop diuretics. Based on recent evidence for the molecular nature of the Na-K-2Cl cotransporter expressed in the mammalian cochlea, the underlying mechanisms of ototoxicity induced by loop diuretics are described.