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 and 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 regular, full-protein diet (9 +/- 6 dB at 8 kHz and 10 +/- 9 dB at 18 kHz) but a significantly higher hearing loss in animals on a low-protein diet (23 +/- 17 dB at 8 kHz and 32 +/- 23 dB at 18 kHz). Animals on the low-protein diet gained significantly less weight than those on the regular diet, and cisplatin treatment lowered the weight gain in both groups. The low-protein diet also significantly reduced cochlear glutathione levels from 180 +/- 50 to 90 +/- 21 nmol/mg protein and serum albumin from 2.32 +/- 0.04 to 1.75 +/- 0.06 g/dl. Cisplatin treatment tended to decrease glutathione and serum albumin in animals on a full-protein 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. Furthermore, serum platinum levels did not differ between animals on either diet, ruling out a potential influence of altered pharmacokinetics on ototoxicity. These results suggest that the metabolic state of the animal is a risk factor for cisplatin ototoxicity.
Lautermann
J
J
Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan, Ann Arbor 48109-0506, USA.
Song
B
B
McLaren
J
J
Schacht
J
J
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D001806:Blood Urea Nitrogen; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D003051:Cochlea / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003404:Creatinine / Q000097:blood; D004044:Dietary Proteins / Q000008:administration & dosage*; D005978:Glutathione / Q000378:metabolism; D006168:Guinea Pigs; D034381:Hearing Loss / Q000139:chemically induced; D007279:Injections, Subcutaneous; D008297:Male; D010984:Platinum / Q000097:blood; D012709:Serum Albumin / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects
D000970:Antineoplastic Agents; D004044:Dietary Proteins; D012709:Serum Albumin; D010984:Platinum; D003404:Creatinine; D005978:Glutathione; D002945:Cisplatin