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

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

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 supplements [83–89].
