Mechanism and Prevention of Ototoxicity Induced by Aminoglycosides

Abstract

Aminoglycosides, a class of clinically important drugs, are widely used worldwide against gram-negative bacterial infections. However, there is growing evidence that aminoglycosides can cause hearing loss or balance problems. In this article, we mainly introduce the main mechanism of ototoxicity induced by aminoglycosides. Genetic analysis showed that the susceptibility of aminoglycosides was attributable to mutations in mtDNA, especially A1555G and C1494T mutations in 12S rRNA. In addition, the overexpression of NMDA receptors and the formation of free radicals also play an important role. Understanding the mechanism of ototoxicity induced by aminoglycosides is helpful to develop new therapeutic methods to protect hearing. In this article, the prevention methods of ototoxicity induced by aminoglycosides were introduced from the upstream and downstream aspects.

Keywords: aminoglycosides; hearing loss; mechanism; ototoxicity; prevention.

Figure 1

Internal and external pathway that induce apoptosis. The external pathway, the ligand binds to the death receptor to active it, which in turn induces a cascade of caspase-8 and caspase-3, leading to apoptosis. The internal pathway, some death signals, such as stress, DNA damage and faulty cell signaling, can induce mitochondria to release cytochrome c, which may form apoptotic bodies, which in turn activate caspase-3 and lead to apoptosis.

Figure 2

Aminoglycoside induce activation of JNK and then induces apoptosis. Aminoglycosides enter the outer hair cells, induce the production of ROS. In response to ROS and then activate JNK, they are translocated into the nucleus and activate some genes, which in turn induce mitochondria to release cytochrome c and induce cell apoptosis.