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首页> 外文期刊>Laboratory investigation >Salicylate Protects Hearing and Kidney Function from Cisplatin Toxicity without Compromising its Oncolytic Action
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Salicylate Protects Hearing and Kidney Function from Cisplatin Toxicity without Compromising its Oncolytic Action

机译：水杨酸酯可保护听力和肾脏功能免受顺铂毒性的影响，而不会损害其溶瘤作用

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Salicylate has recently been demonstrated to protect against the auditory and vestibular side effects of aminoglycoside antibiotics. Similarities in the toxic mechanisms suggest salicylate as a treatment strategy to prevent the ototoxic side effects of cisplatin (CDDP). We first tested protection of the inner ear in Wistar rats receiving a single infusion of 16 mg CDDP/kg body weight with or without treatment with 100 mg/kg salicylate (bid) for 5 days beginning one day before the CDDP infusion. Cisplatin induced a threshold shift of more than 30 dB (at 14 kHz; measured by auditory evoked brain stem response) that was significantly reduced by salicylate. We then examined the protective potential of salicylate on the cochlea, peripheral nerves, and kidney in a rat model of breast cancer—Fisher344 rats implanted with highly metastatic MTLn3 breast cancer cells. Animals received 3 5 mg CDDP/kg (given every third day), and salicylate was administered at 100 mg/kg (bid) from 2 days before to 3 days after CDDP treatment. Salicylate significantly attenuated the CDDP-induced threshold shift from approximately 20 dB (at 16 and 24 kHz) to approximately 5 dB, and drastically reduced the loss of cochlear outer hair cells. Likewise, salicylate protected kidney function (measured as plasma blood urea nitrogen and creatinine levels) from CDDP toxicity. Protection of nerve conduction velocities of both sensory and motor nerves was minimal. The chemotherapeutic efficacy of CDDP on suppression of tumor mass and cancer cell metastasis remained unaffected by salicylate. The results suggest that administration of salicylate may become the basis of an effective therapeutic intervention against the ototoxic and nephrotoxic side effects associated with CDDP chemotherapy.
机译：最近已证明水杨酸酯可防止氨基糖苷类抗生素对听觉和前庭的副作用。在毒性机制上的相似性表明，水杨酸盐是预防顺铂（CDDP）耳毒性副作用的治疗策略。我们首先在接受Wistar大鼠的Wistar大鼠中测试了其对内耳的保护，该大鼠在CDDP输注前一天开始5天，接受或不接受100 mg / kg水杨酸酯（出价）的治疗，持续5天。顺铂引起的阈值漂移超过30 dB（在14 kHz时;通过听觉诱发的脑干反应测量），而水杨酸酯可明显降低阈值漂移。然后，我们在乳腺癌大鼠模型-植入了高度转移性MTLn3乳腺癌细胞的Fisher344大鼠中，研究了水杨酸酯对耳蜗，周围神经和肾脏的保护潜力。动物接受3 5 mg CDDP / kg（每三天给予），从CDDP治疗前2天至治疗后3天以100 mg / kg（水平）施用水杨酸盐。水杨酸盐将CDDP引起的阈值位移从大约20 dB（在16和24 kHz时）显着衰减到大约5 dB，并大大减少了耳蜗外毛细胞的损失。同样，水杨酸盐可保护肾脏功能（以血浆尿素氮和肌酐水平衡量）免受CDDP毒性。感觉神经和运动神经的神经传导速度的保护作用很小。水杨酸盐对CDDP抑制肿瘤块和癌细胞转移的化学治疗作用保持不变。结果表明，水杨酸盐的施用可能成为针对与CDDP化疗相关的耳毒性和肾毒性副作用的有效治疗干预措施的基础。

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