Kanamycin Sulfate

Kanamycin Sulfate is a broad-spectrum aminoglycoside antibiotic that exhibits potent antibacterial activity against a wide range of both Gram-positive and Gram-negative bacteria, including many multidrug-resistant strains. Kanamycin Sulfate commonly used in clinical settings to treat severe infections^[1-2]. Kanamycin Sulfate interferes with bacterial protein synthesis by binding to the 30S subunit of the bacterial ribosome, resulting in the production of nonfunctional or abnormal proteins^[3]. Additionally, Kanamycin Sulfate has been shown to cause hearing loss in rats^[4].

In vitro, treatment with Kanamycin Sulfate (50mg/kg) in combination with exogenous pyruvate or glucose significantly reduces the survival rate of resistant strains and enhances their sensitivity to Kanamycin Sulfate ^[5]. After 24 hours of treatment with Kanamycin Sulfate (25μg/mL), HeLa cells exhibited significant changes in the ratio of phosphatidylinositols (PI) to cardiolipins (CL), with an increase in PI and a decrease in CL. Moreover, Kanamycin Sulfate treatment led to a reduction in mitochondrial membrane potential and changes in mitochondrial morphology, characterized by shorter and fewer mitochondrial branches^[6].

In vivo, a single intraperitoneal injection of Kanamycin Sulfate (200mg/kg) in combination with Furosemide (400mg/kg) was administered to 8-week-old male C57/BL6 mice. This treatment significantly elevated auditory brainstem response (ABR) thresholds and resulted in the loss of hair cells (HC) and spiral ganglion neurons (SGN)^[7]. In another study, Kanamycin Sulfate (200mg/kg) in combination with Furosemide (50mg/ml) was applied via a single intratympanic injection to guinea pigs for either 1 or 2 hours. The results showed that 94% of ears treated for 2 hours experienced complete hearing loss, compared to 80% of ears treated for 1 hour. The hearing loss remained stable and irreversible during the 26-week follow-up period^[8].

References:
[1] Hotta K, Kondo S. Kanamycin and its derivative, arbekacin: significance and impact. J Antibiot (Tokyo). 2018 Mar;71(4):417-424.
[2] Pindell MH. The pharmacology of kanamycin--a review and new developments. Ann N Y Acad Sci. 1966 Jun 14;132(2):805-10.
[3] Chen Z, Liu X, Chen L, et al. Deglycosylation Inactivation Initiated by a Novel Periplasmic Dehydrogenase Complex Provides a Novel Strategy for Eliminating the Recalcitrant Antibiotic Kanamycin. Environ Sci Technol. 2023 Mar 14;57(10):4298-4307.
[4] Wang M, Han Y, Wang X, et al. Characterization of EGR-1 Expression in the Auditory Cortex Following Kanamycin-Induced Hearing Loss in Mice. J Mol Neurosci. 2021 Nov;71(11):2260-2274.
[5] Peng B, Su YB, Li H, et al. Exogenous alanine and/or glucose plus kanamycin kills antibiotic-resistant bacteria. Cell Metab. 2015 Feb 3;21(2):249-262.
[6] Rebollo-Ramirez S, Krokowski S, Lobato-Márquez D, et al. Intact Cell Lipidomics Reveal Changes to the Ratio of Cardiolipins to Phosphatidylinositols in Response to Kanamycin in HeLa and Primary Cells. Chem Res Toxicol. 2018 Aug 20;31(8):688-696.
[7] Nitta Y, Kurioka T, Mogi S, et al. Suppression of the TGF-β signaling exacerbates degeneration of auditory neurons in kanamycin-induced ototoxicity in mice. Sci Rep. 2024 May 13;14(1):10910.
[8] Bako P, Gerlinger I, Wolpert S, et al. The ototoxic effect of locally applied kanamycin and furosemide in guinea pigs. J Neurosci Methods. 2022 Apr 15;372:109527.

Kanamycin Sulfate是一种广谱氨基糖苷类抗生素，对多种革兰氏阳性菌和革兰氏阴性菌具有强大的抗菌活性，包括多重耐药菌株。Kanamycin Sulfate在临床中常用于治疗严重感染^[1-2]。Kanamycin Sulfate通过与细菌30S亚基结合，干扰细菌蛋白质合成，从而产生非功能性或异常蛋白质^[3]。此外，Kanamycin Sulfate可能会引起大鼠的听力损伤^[4]。

在体外，Kanamycin Sulfate（50mg/kg）联合外源性丙酮酸或葡萄糖处理，可显著降低耐药菌株的生存率，并增强其对Kanamycin Sulfate的敏感性^[5]。Kanamycin Sulfate（25μg/mL）处理HeLa细胞24小时后，显著改变了磷脂酰肌醇（PI）和心磷脂（CL）的比率，导致PI含量增加，CL含量减少。同时，Kanamycin Sulfate处理还降低了线粒体膜电位，并改变了线粒体形态，使线粒体分支变短且数量减少^[6]。

在体内，Kanamycin Sulfate（200mg/kg）联合Furosemide（400mg/kg）单次腹腔注射用于处理8周龄的C57/BL6雄性小鼠。Kanamycin Sulfate处理显著增加了听觉脑干反应（ABR）阈值，并导致毛细胞（HC）和螺旋神经节神经元（SGN）的丢失^[7]。Kanamycin Sulfate（200mg/kg）联合Furosemide（50mg/ml）通过单次鼓室注射应用于豚鼠，处理时间为1小时或2小时。结果显示，2小时处理组中94%的耳朵出现完全听力丧失，而1小时处理组中80%的耳朵出现完全听力丧失。听力丧失在26周的随访期间保持稳定且不可逆^[8]。