Aminoglycoside antibiotics are widely used for many life-threatening infections. The use of aminoglycosides is often comprised by their deleterious side effects to the kidney and inner ear. A novel semisynthetic antibiotic, etimicin, has good antimicrobial activity against both gram-positive and gram-negative bacteria. But its toxicity profile analysis is still lacking. In the present study, we compared the in vivo toxic effects of three aminoglycosides, gentamicin, amikacin, and etimicin, in zebrafish embryos. We examined the embryotoxicity, nephrotoxicity, and the damage to the neuromast hair cells. Our results revealed that etimicin and amikacin exhibit more developmental toxicities to the young embryos than gentamicin. But at subtoxic doses, etimicin and amikacin show significantly reduced toxicities towards kidney and neuromast hair cells. We further demonstrated that fluorescently conjugated aminoglycosides (gentamicin-Texas red [GTTR], amikacin-Texas red [AMTR], and etimicin-Texas red [ETTR]) all enter the hair cells properly. Inside the hair cells, gentamicin, not etimicin and amikacin, displays robust reactive oxygen species generation and induces apoptosis. Our data support that the different intracellular cytotoxicity underlies the different ototoxicity of the three aminoglycosides and that etimicin is a new aminoglycoside with reduced risk of nephrotoxicity and ototoxicity.

中文翻译：

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一种新的氨基糖苷类依替米星在斑马鱼胚胎中显示出低肾毒性和耳毒性

氨基糖苷类抗生素广泛用于许多危及生命的感染。氨基糖苷类的使用通常包括它们对肾脏和内耳的有害副作用。一种新型的半合成抗生素依替米星对革兰氏阳性菌和革兰氏阴性菌均具有良好的抗菌活性。但其毒性特征分析仍然缺乏。在本研究中，我们比较了三种氨基糖苷类药物庆大霉素、阿米卡星和依替米星在斑马鱼胚胎中的体内毒性作用。我们检查了胚胎毒性、肾毒性和对神经母细胞毛细胞的损伤。我们的研究结果表明，依替米星和阿米卡星对年轻胚胎的发育毒性高于庆大霉素。但在亚毒性剂量下，依替米星和阿米卡星对肾脏和神经瘤毛细胞的毒性显着降低。我们进一步证明荧光偶联的氨基糖苷类（庆大霉素-德克萨斯红 [GTTR]、阿米卡星-德克萨斯红 [AMTR] 和依替米星-德克萨斯红 [ETTR]）都能正确进入毛细胞。在毛细胞内，庆大霉素，而不是依替米星和阿米卡星，显示出强大的活性氧生成并诱导细胞凋亡。我们的数据支持不同的细胞内细胞毒性是三种氨基糖苷类不同耳毒性的基础，并且依替米星是一种新的氨基糖苷类，具有降低的肾毒性和耳毒性风险。显示强大的活性氧生成并诱导细胞凋亡。我们的数据支持不同的细胞内细胞毒性是三种氨基糖苷类不同耳毒性的基础，并且依替米星是一种新的氨基糖苷类，具有降低的肾毒性和耳毒性风险。显示强大的活性氧生成并诱导细胞凋亡。我们的数据支持不同的细胞内细胞毒性是三种氨基糖苷类不同耳毒性的基础，并且依替米星是一种新的氨基糖苷类，具有降低的肾毒性和耳毒性风险。