The effects of cisplatin and 5-fluorourasil on prestin levels and hearing functions in experimental animal study

Cisplatin (cis ‐diamminedichloroplatin‐II, CP) and 5-fluorouracil (FL) are effective chemotherapeutic drugs that are frequently used together in the treatment of cancer. These drugs used may show ototoxic side effects such as hearing loss and tinnitus. These agents may cause irreversible damage in the outer hair cells (OHC) of the cochlea, especially through apoptosis. Prestin is a motor protein that is highly present as a membrane protein in the OHC's of the cochlea and produces electromotility with rapid length change, and may primarily be affected by these toxic agents. Today, early detection of hearing loss and tinnitus due to various kalıcıpre-evaluate the effects of an ototoxic agent affecting OHC on hearing functions. Early detection of the damage in OHC will allow the treatment to be more effective and resultable. The aim of this study is to reveal the effects of the single or combined use of CP and FL, which are frequently used in the treatment of various cancer types, on hearing functions and to investigate the relationship between this effect and serum prestin levels. For this purpose, 56 rats (rats) were equally divided into control, CP, FL and CP + FL groups and hearing tests were performed before and after treatment. After the treatments, half of the subjects in each group were decapitated on day 3 and the other half on day 14, and blood and cochlea samples were taken, and plasma prestin levels and histopathological changes were examined. With respect to day 3 prestin immunoreactivity, an increase was observed in the CP (p<0.01) and CP + FL (p<0.01) groups, while no difference was observed in the FL group (p>0.05). The changes observed in the CP (p>0.05), CP + FL (p>0.05) and FL (p>0.05) groups with respect to day 14 findings were insignificant. However, in the CP and CP + FL groups (p<0.01), it was determined that the immunoreactivity of prestin on day 14 decreased compared to day 3. In terms of day 3 apoptotic cell findings, an increase was observed in TUNEL positivity in the CP (p<0.001) and CP + FL (p<0.001) groups, while no difference was observed in the FL group (p>1,000). In terms of day 14 findings, an increase was observed in TUNEL positivity in the CP (p<0.001) and CP + FL (p<0.001) groups, while no difference was observed in the FL group (p>0.05). However, no statistically significant difference was observed between day 3 and 14 in TUNEL positivenesses of the CP, CP + FL and FL groups. There was no difference between the groups in ABR measurement values on day 3. An increase on day 14 findings was detected in CP, CP + FL and FL groups (p<0.05). However, no difference was observed in CP, CP + FL and FL groups with respect to days 3 and 14 values. An increase was observed in day 3 plasma prestin findings of CP and CP + FL groups (p<0.01), but no difference in FL group. No difference was observed in CP, CP + FL and FL groups in day 14 findings. However, a decrease was determined in day 14 values of CP and CP + FL groups (p<0.05) compared to day 3 values.