Gentamicin (Synonyms: Gentamicin; Centicin; Lyramycin; Oksitselanim; Refobacin; Septigen; Uromycine; )

Gentamicin is an aminoglycoside bactericidal antibiotic that is effective against Gram-negative bacterial infections. Gentamicin binds to the 30S subunit of the bacterial ribosome to inhibit protein synthesis.

Exposure to 100 uM gentamicin exhibited a muscimol EC50 of 80 6nM (n=10). The EC50 value obtained in the absence of gentamicin was 124 11nM (n=10). The 35% increase in potency suggests network sensitization to muscimol in the presence of gentamicin. Action potential (AP) waveform analyses of neurons exposed to gentamicin demonstrated a concentration-dependent decrease in AP amplitudes (extracellular recordings), possibly reflecting gentamicin effects on voltage-gated ion channels^[3].When design, synthesis characterization and evaluation of a fluorescent conjugate of the aminoglycoside antibiotic gentamicin, Related gentamicin conjugates studied quench in live kindney cells, and have been largely restricted to use in fixed (delipidated) cells^[5]. Gentamicin increases mitochondria-specific oxidative stress and rapidly destroys CORE, leading to marked mitochondrial fragmentation and ER-mitochondrial dissociation, which leads to poor UPR activation and proteotoxic cell death^[1].Cell-penetrating peptides (CPPs) mediate the internalization of biologically active molecules into the cytoplasm.CPPs were covalently conjugated to gentamicin, and CPP-gentamicin conjugates were used to target infected cells to kill multiple intracellular Gram-negative pathogenic bacteria^[4]. Strong PKB/Akt activation was observed in the organ of Corti following exposure to 50µM gentamicin for 6 h. In addition, PKC activation by 12-O-tetradecanoylphorbol-13-acetate protected outer hair cells from gentamicin induced cell death^[6].

In Pigmented guinea pigs, Gentamicin was detected in every cochlear cell type, but with spatiotemporal variability. One day after application, an intense staining reaction was found in all cell types except the spiral ganglion cells and the stria vascularis. Six days later, gentamicin staining intensities were additionally reduced in the nerve fibers and the spiral ligament^[2].In organ culture that metformin blocks the gentamicin-induced translocation of endonuclease G into the nucleus of outer hair cells and attenuates hair cell loss. In vivo, gentamicin treatment with 80, 100, or 130mg/kg body weight for 14 days induced significant threshold shifts^[7].

References:
[1]: Igwebuike C, Yaglom J, et,al. Cross organelle stress response disruption promotes gentamicin-induced proteotoxicity. Cell Death Dis. 2020 Apr 3;11(4):217. doi: 10.1038/s41419-020-2382-7. PMID: 32245975; PMCID: PMC7125232.
[2]: Heinrich UR, Schmidtmann I, et,al. Cell-specific accumulation patterns of gentamicin in the guinea pig cochlea. Hear Res. 2015 Aug;326:40-8. doi: 10.1016/j.heares.2015.03.010. Epub 2015 Apr 13. PMID: 25882166.
[3]: Hamilton KS, Gopal KV, et,al. Pharmacological response sensitization in nerve cell networks exposed to the antibiotic gentamicin. Eur J Pharmacol. 2017 Jan 5;794:92-99. doi: 10.1016/j.ejphar.2016.11.017. Epub 2016 Nov 15. PMID: 27864104.
[4]: Gomarasca M, F C Martins T, et,al.Bacterium-Derived Cell-Penetrating Peptides Deliver Gentamicin To Kill Intracellular Pathogens. Antimicrob Agents Chemother. 2017 Mar 24;61(4):e02545-16. doi: 10.1128/AAC.02545-16. PMID: 28096156; PMCID: PMC5365713.
[5]: Escobedo JO, Chu YH, et,al. Live cell imaging of a fluorescent gentamicin conjugate. Nat Prod Commun. 2012 Mar;7(3):317-20. PMID: 22545403; PMCID: PMC3376166.
[6]: Chung WH, Pak K, et,al. A PI3K pathway mediates hair cell survival and opposes gentamicin toxicity in neonatal rat organ of Corti. J Assoc Res Otolaryngol. 2006 Dec;7(4):373-82. doi: 10.1007/s10162-006-0050-y. Epub 2006 Oct 20. PMID: 17053865; PMCID: PMC2504631.
[7]: Oishi N, Kendall A, et,al. Metformin protects against gentamicin-induced hair cell death in vitro but not ototoxicity in vivo. Neurosci Lett. 2014 Nov 7;583:65-9. doi: 10.1016/j.neulet.2014.09.028. Epub 2014 Sep 18. PMID: 25240593; PMCID: PMC4253637.