Ototoxic and Nephrotoxic Effects of Combined Treatment with cis -Diamminedichloroplatinum and Kanamycin in the Guinea Pig

Abstract

Ototoxic and nephrotoxic potentiation with concomitant cis-diamminedichloroplatinum, or cis-platinum II (CSP), and aminoglycoside therapy was investigated in the guinea pig. We evaluated possible potentiation of the toxic effects of CSP and kanamycin compared with CSP alone in the inner ear and kidney and quantitatively localized CSP in the cochlea with gamma emission analysis of ^195mPt. Kanamycin-treated animals demonstrated cytocochleograms and ABR waveforms, absolute latencies, and interwave latencies for waves I, II, and III similar to control animals at our maximum level of acoustic stimulation. CSP treatment produced 60% to 70% mean outer hair cell (OHC) loss in the basal turn of the cochlea, a reduction In ABR waveform and amplitude, and an Increase in latencies of ABR waves I, II, and III. Combined CSP and kanamycin treatment produced 90% to 100% mean OHC loss in all rows of the basal turn of the cochlea, with no discernible ABR waveform corresponding to the region stimulated by a 4500 to 7000 Hz acoustic click. Combined treatment produced the most significant cortical medullary tubular necrosis and interstitial nephritis. Furthermore, this study reports for the first time localization of platinum in the inner ear.