DIET IS A RISK FACTOR IN CISPLATIN OTOTOXICITY

This study demonstrates that cisplatin ototoxicity depends on dietary factors and correlates with decreased levels of cochlear glutathione a nd serum albumin. After 12 days of injections, cisplatin (1 mg/kg body weight, s.c.) caused a small hearing loss in guinea pigs fed a regula r, full-protein diet (9 +/- 6 dB at 8 kHz and 10 +/- 9 dB at 18 kHz) b ut a significantly higher hearing loss in animals on a low-protein die t (23 +/- 17 dB at 8 kHz and 32 +/- 23 dB at 18 kHz). Animals on the l ow-protein diet gained significantly less weight than those on the reg ular diet, and cisplatin treatment lowered the weight gain in both gro ups. The low-protein diet also significantly reduced cochlear glutathi one levels from 180 +/- 50 to 90 +/- 21 nmol/mg protein and serum albu min from 2.32 +/- 0.04 to 1.75 +/- 0.06 g/dl. Cisplatin treatment tend ed to decrease glutathione and serum albumin in animals on a full-prot ein diet but not on the low-protein diet. Renal function was assessed by measuring blood urea nitrogen (BUN) and serum creatinine. While BUN and creatinine values indicated some cisplatin-induced nephrotoxicity , there was no correlation with the severity of ototoxicity. Furthermo re, serum platinum levels did not differ between animals on either die t, ruling out a potential influence of altered pharmacokinetics on oto toxicity. These results suggest that the metabolic state of the animal is a risk factor for cisplatin ototoxicity.