Department of Otolaryngology and Laryngological Oncology, Medical University of Lublin, Lublin, Poland.
Department of Otolaryngology and Laryngological Oncology, Medical University of Lublin, Lublin, Poland.
Pharmacol Rep. 2019 Apr;71(2):351-356. doi: 10.1016/j.pharep.2019.01.002. Epub 2019 Jan 4.
Drug-induced ototoxicity is still a main clinical problem in otolaryngology. It is widely known that aminoglycoside antibiotics combined with loop diuretics significantly contribute to permanent ototoxicity. The aim of this study was to find out whether ascorbic acid (vitamin C) is able to reverse or alleviate ototoxicity evoked by systemic (ip) administration of combination of amikacin and furosemide in experimental male albino Swiss mice.
Ototoxic combination of amikacin and furosemide was isobolographically evaluated based on the hearing threshold decreasing doses by 20% and 50% (TDD and TDD), respectively. Linear regression analysis was used to determine the TDD and TDD values for amikacin, furosemide, vitamin C administered alone and in combination (at the fixed-ratio of 1:1).
Vitamin C (in a dose of 500 mg/kg, ip) alleviated the impairment in hearing threshold evoked by combined ip administration of amikacin and furosemide (at the fixed-ratio of 1:1) in mice by reducing TDD values from 49.82 to 21.56 (p < 0.01). In contrast, vitamin C (500 mg/kg, ip) had no significant effect on TDD values for the combination of amikacin and furosemide at the fixed-ratio of 1:1.
Vitamin C administered together with ototoxic drug combination of amikacin and furosemide reduced ototoxicity evoked by this two-drug combination in the experimental mice.
药物性耳毒性仍然是耳鼻喉科的一个主要临床问题。众所周知，氨基糖苷类抗生素与袢利尿剂联合使用会显著导致永久性耳毒性。本研究旨在探讨抗坏血酸（维生素 C）是否能够逆转或减轻氨基糖苷类抗生素和呋塞米联合全身（ip）给药在实验性雄性白化瑞士小鼠中引起的耳毒性。
基于氨基糖苷类抗生素和呋塞米分别引起听力阈值降低 20%和 50%（TDD 和 TDD）的剂量，对氨基糖苷类抗生素和呋塞米的耳毒性组合进行等辐射评价。线性回归分析用于确定氨基糖苷类抗生素、呋塞米、单独给予和联合给予（固定比例为 1:1）的维生素 C 的 TDD 和 TDD 值。
维生素 C（剂量为 500mg/kg，ip）通过降低 TDD 值（从 49.82 降至 21.56，p<0.01），减轻了氨基糖苷类抗生素和呋塞米联合 ip 给药在小鼠中引起的听力阈值损伤。相比之下，维生素 C（500mg/kg，ip）对氨基糖苷类抗生素和呋塞米联合固定比例为 1:1 的 TDD 值没有显著影响。
在实验性小鼠中，与氨基糖苷类抗生素和呋塞米的耳毒性药物组合一起给予维生素 C，可降低该两种药物组合引起的耳毒性。
