Effect of ghrelin on cysplatin autotoxicity

The aim of this study is to evaluate whether ghrelin has a protective effect against ototoxicity, one of the side effects of cisplatin. The study was conducted on 24 healthy adult male Sprague Dawley rats, weighing between 225-300 grams. The subjects were randomly divided into 4 groups of 6 rats each. Group 1 (Control) received 1 ml/day of intraperitoneal (ip) saline solution for seven days. Group 2 (Cisplatin) received ip cisplatin at doses of 10 mg/kg for two days, reaching a cumulative dose of 20 mg/kg. Group 3 (G40) received ip cisplatin at doses of 10 mg/kg for two days, reaching a cumulative dose of 20 mg/kg, and additionally, ip ghrelin at 40 μg/kg for seven days. Group 4 (G80) received i.p cisplatin at doses of 10 mg/kg for two days, reaching a cumulative dose of 20 mg/kg, and additionally, i.p ghrelin at 80 μg/kg for seven days. Before the study, all subjects underwent DPOAE and ABR tests. On the 4th day of the study, after DPOAE and ABR tests were performed on all subjects, half of the subjects in each group were decapitated after serum samples were taken, and their cochleae were removed for immunohistochemical examination. The same procedures were then performed on the remaining subjects on the 8th day. According to the DPOAE test results, all subjects had similar DPOAE test results on day 0. On days 4 and 8, a significant decrease in SNR values was observed in both ears of group 2. On days 4 and 8 of the study, there was no significant decrease in SNR at frequencies of 552, 728, 1270, 2207, and 6694 Hz in the right ear, and at frequencies of 552, 728, 2207, 6694, and 8838 Hz in the left ear for groups 3 and 4. In the ABR test, no statistically significant difference was observed in the prolongation of V wave latencies when comparing group 2 with groups 3 and 4 on day 4 of the study. However, on day 8, the prolongation of V wave latencies was significantly less in groups 3 and 4. Regarding the biochemical findings, on days 4 and 8 of the study, serum TOS levels increased in group 2, while TAS levels increased in groups 3 and 4. According to the findings of our study, compared to the pre-study period, it was observed that there was cisplatin ototoxicity in groups 2, 3, and 4, but the effects were less pronounced in groups 3 and 4 compared to the other groups. Based on these findings, we suggest that ghrelin could be used to protect against cisplatin ototoxicity.