**Glossary of terms**

It is likely that the ototoxic effect of immunosuppressants depends on the length of time of intake. Groups studying noise-induced hearing loss have successfully used cyclosporine A and tacrolimus to protect the auditory epithelium in mice from the noise-induced injury [64]. However, the dosage was single and not–like in the case of transplant patients–years long.

The treatment of hearing impairment occurring in organ transplant recipients includes hearing aids and cochlear implantation [65]. However, one should not ignore the fact that these patients are immunocompromised, and therefore, the risk of wound infection after CI should

The auditory system requires a lot of energy produced in mitochondria [66–69]. Mitochondrial pathologies induced by genetic mutations are often associated with hearing loss [70–72]. Similarly, substances known to damage mitochondria such as aminoglycosides or cisplatin are known as ototoxic and contribute significantly to the hearing loss and tinnitus [73].

The substances listed in the present chapter can all damage the mitochondria. The damaging mechanism varies, and for instance, IFN-alpha impairs the transcription of mitochondrial DNA, whereas nucleoside analogues impair the replication of mitochondrial DNA [74]. In agreement with this, severe mitochondrial toxicity manifested by hyperlactatemia and pancreatitis was described in some cases involving patients with HIV/hepatitis C virus treated with pegylated interferon and ribavirin [75]. Paracetamol was also shown to have negative effect on mitochondria by inducing overproduction of reactive oxygen species (ROS) and inducing endoplasmic reticulum stress [47, 76]. Methadone was shown to impair synthesis of mitochondrial ATP leading to bioenergetics crisis of the affected organism [77]. The reverse transcriptase inhibitors used to slow down the replication of HIV virus were likewise demonstrated to induce mitochondrial toxicity [78, 79]. Lastly, cyclosporine A was shown to inhibit adenine nucleotide net transport into the mitochondria [80], whereas tacrolimus was associ-

**7. Mitochondrial toxicity: common denominator of ototoxic drugs**

ated with decreasing the levels of oxidative phosphorylation in mitochondria [81].

supplements [83–89].

242 Advances in Clinical Audiology

**8. Conclusions**

Since the negative effect of various drugs on mitochondria likely results in a damage of hearing, it is plausible that the mitochondria-supporting substances (such as coenzyme Q10, vitamin B12 with folic acid, sirtuin and many others) given as auxiliary therapy could protect the sense of hearing in patients with hepatitis, HIV, transplant patients or painkiller or PDE5 inhibitor users. In fact, targeting mitochondria is becoming increasingly popular [82], and there were some successful attempts in treatment of hearing conditions using mitochondrial

The appearance of new drugs to treat ever more conditions is an inevitable and welcomed progress of medical and pharmaceutical sciences. However, assuring the drug safety in terms

be taken under consideration during postsurgical management.


