Lautermann J, Song B, McLaren J, Schacht J
Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan, Ann Arbor 48109-0506, USA.
Hear Res. 1995 Aug;88(1-2):47-53. doi: 10.1016/0378-5955(95)00097-n.
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.
本研究表明,顺铂耳毒性取决于饮食因素,且与耳蜗谷胱甘肽水平和血清白蛋白水平降低相关。注射12天后,顺铂(1毫克/千克体重,皮下注射)使喂食常规全蛋白饮食的豚鼠出现轻度听力损失(8千赫兹时为9±6分贝,18千赫兹时为10±9分贝),但使低蛋白饮食的动物听力损失显著更高(8千赫兹时为23±17分贝,18千赫兹时为32±23分贝)。低蛋白饮食的动物体重增加明显少于常规饮食的动物,顺铂治疗降低了两组动物的体重增加。低蛋白饮食还使耳蜗谷胱甘肽水平从180±50纳摩尔/毫克蛋白显著降至90±21纳摩尔/毫克蛋白,血清白蛋白从2.32±0.04克/分升降至1.75±0.06克/分升。顺铂治疗倾向于降低全蛋白饮食动物的谷胱甘肽和血清白蛋白水平,但对低蛋白饮食动物则无此影响。通过测量血尿素氮(BUN)和血清肌酐评估肾功能。虽然BUN和肌酐值表明存在一些顺铂诱导的肾毒性,但与耳毒性的严重程度无关。此外,两种饮食的动物血清铂水平无差异,排除了药代动力学改变对耳毒性的潜在影响。这些结果表明,动物的代谢状态是顺铂耳毒性的一个危险因素。