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Insights into Ototoxicity
Author(s) -
Humes H. David
Publication year - 1999
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1999.tb00278.x
Subject(s) - ototoxicity , nephrotoxicity , endolymph , aminoglycoside , chemistry , inner ear , cochlea , furosemide , kidney , pharmacology , renal physiology , endocrinology , medicine , biophysics , biochemistry , renal function , antibiotics , anatomy , biology , cisplatin , organic chemistry , chemotherapy
The most common ototoxic compounds in clinical practice are aminoglycoside antibiotics, cisplatin, and loop diuretics (ethacrynic acid and furosemide). These agents also have substantial renal effects in the form of nephrotoxicity or diuresis. The understanding of these renal effects may provide insight into ototoxic mechanisms. For aminoglycosides, the renal proximal tubule cell is susceptible due to high concentration achieved and slow clearance with direct effects on phosphoinositide binding and mitochondrial bioenergetics. Pathogenesis appears to involve iron‐induced free‐radical formation, since iron chelators prevent nephrotoxicity. Analogous effects of aminoglycosides on the inner and outer hair cells have been observed. Cisplatin is also highly concentrated in the proximal tubule cell. Less is known about the direct toxic effects of this agent on renal cells. Insights into mechanisms on renal tubule cells could be directly relevant to the inner ear. The loop diuretics are direct ihibitors of the Na + ‐K + ‐2CI − cotransport system, which also exists in the marginal and dark cells of the stria vascularis, which are responsible for endolymph secretion. The ototoxicity of these agents may be indirect, due to changes in ionic composition and fluid volume within the endolymph.