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.
Highlights
Hearing loss is the most common sensory disorder worldwide
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
Summary
Hearing loss is the most common sensory disorder worldwide. The World Health Organization estimates that around 466 million people worldwide suffer from disabling hearing loss and that by 2050 more than 900 million people will have this condition. Studies have found that when mitochondrial DNA (especially 12S rRNA) is mutated, it increases the binding to aminoglycosides, inhibits the synthesis of mitochondrial proteins and increases the formation of free radicals, which in turn affects hearing (Qian and Guan, 2009) This suggests that mitochondrial DNA mutations are associated with susceptibility to aminoglycosides. Substrates of ERK and JNK subfamilies of MAPK, c-Fos and c-Jun, form AP-1 transcription factor complexes (Xia et al, 1996) It can be seen from the above studies that NMDA plays an important role in the ototoxicity induce by aminoglycosides, which is worth further exploration. ROS induced by aminoglycosides can cause the release of cytochrome c in mitochondria and cascade activation of caspase, leading to substrate proteolysis and cell collapse. It may be more effective to inhibit these ototoxicinducing pathways together
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