title: Diet is a risk factor in cisplatin ototoxicity.
abstract: 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.
authors.affiliation: Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan, Ann Arbor 48109-0506, USA.
authors.forename: J
authors.initials: J
authors.lastname: Lautermann
authors.forename: B
authors.initials: B
authors.lastname: Song
authors.forename: J
authors.initials: J
authors.lastname: McLaren
authors.forename: J
authors.initials: J
authors.lastname: Schacht
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D004044:Dietary Proteins; D012709:Serum Albumin; D010984:Platinum; D003404:Creatinine; D005978:Glutathione; D002945:Cisplatin