Effect of Albumin-Bound Furosemide on the Endocochlear Potential of the Chinchilla: Alleviation of Furosemide-Induced Ototoxicity

Abstract

\s=b\The effects of albumin-unbound furosemide and albumin-bound furosemide on the cochlear function were compared by the continuous observation of the endocochlear potential (EP) in the chinchilla using the microelectrode method. The EP depression following the intravenous injection of 50 mg/kg of furosemide was 108.5 \m=+-\2.7 mV, while the addition of 1.0 and 1.3 g/kg of albumin induced the EP depression to be 35.0 \m=+-\4.8 and 8.1 \ m=+-\ 1.9 mV, respectively, and both prolonged the time to attain the minimum EP. However, there was no difference in the recovery time of the EP between the two groups. The results indicate that access to the site of furosemide action in the cochlea is dependent on the unbound fraction of furosemide and that the albumin-bound furosemide alleviates the EP depression induced by furosemide alone with the augmentation of diuresis.

Conditioning the Cochlea to Facilitate Survival and Integration of Exogenous Cells into the Auditory Epithelium

“…The transient nature of furosemide effects have been shown to last for hours 10,11 but certainly not for 7 days, which is the longest survival time we examined. In addition, we have shown here that the EP in normal animals that receive the conditioning treatment can recover.…”

“…In addition, we have shown here that the EP in normal animals that receive the conditioning treatment can recover. Thus, once the effects of furosemide subside and the SV regains its function, potassium levels in the SM begin to recover and return to normal within hours [11][12][13] as does the EP. [13][14][15] Our finding that implanted cells survive despite the return of a potassium rich fluid around them suggests that gradual return to normal conditions in SM is compatible with survival of transplanted cells.…”

Uniform comparison of several drugs which provide protection from noise induced hearing loss

“…Since a single injection of furosemide at an appropriate time (30 minutes) before the broadband noise exposure (but not after) was effective in providing protection, it is likely that the protective effect of furosemide is related to its reversible depression of the endocochlear potential [14], which is one of the main electrochemical gradients required for auditory transduction, and reduction in the magnitude of the endocochlear potential. This leads to depression of the cochlear amplifier [15], with smaller active displacements of the outer hair cells (OHCs) [16] within a short period after its injection.…”

Ototoxic effects and mechanisms of loop diuretics

“…Diuretic-induced inhibition of the Na-K-2Cl cotransport system in the ascending limb of Henle's loop in the kidney suggested that this cotransporter might play an important role in the stria ( Burg et al., 1973 , Sellick and Johnstone, 1975 , Shindo et al., 1992 ). Indeed, many studies indicate that diuretics and anoxia affect the Na-K-2Cl cotransporter in strial marginal cells ( Bosher, 1979 , Bosher, 1980 , Ikeda and Morizono, 1989b , Ikeda and Morizono, 1989c , Ikeda and Morizono, 1989a , Shindo et al., 1992 , Xu et al., 1994 , Wangemann et al., 1995 , Ikeda et al., 1997 ), however, inhibition of this cotransporter occurs much later that the immediate reduction of EP ( Bosher, 1980 ).…”