Reduced nutritional status enhances ototoxicity

Abstract

This study investigates whether the nutritional state of guinea pigs is a risk factor for the ototoxic side effects of cisplatin, gentamicin, and gentamicin in combination with ethacrynic acid. A normal nutritional state was maintained with a standard 18.5% protein diet while nutritional deficiency was produced by feeding a 7% protein diet. Hearing loss was measured by auditory evoked brainstem responses. Guinea pigs on the low protein diet had a significantly higher drug-induced hearing loss. Cisplatin-induced hearing loss was 32 dB in undernourished animals but 10 dB in normal animals (18 kHz). The difference for gentamicin was 74 dB versus 42 dB (18 kHz). Gentamicin in combination with 20 mg ethacrynic acid/kg body weight produced a hearing loss of 95 dB in animals on a low protein diet and 12 dB in animals on a full protein diet. The enhanced ototoxicity was not based on differences in drug pharmacokinetics since serum levels of platinum and gentamicin did not differ between the groups. These results demonstrate that the severity of ototoxic side effects is influenced by nutritional factors. They also imply that animals on a restricted diet may be a more appropriate model for severely compromised patients undergoing pharmacotherapy.