Seyit Mehmet Ceylan1, Erdal Uysal2, Serdar Altinay3, Efe Sezgin4, Nagihan Bilal5, Emine Petekkaya6, Mehmet Dokur7, Mahmut Alper Kanmaz8, Mustafa Emre Gulbagci3. 1. Department of Otorhinolaryngology, Faculty of Medicine, Sanko University, Incilipinar Mah. Ali Fuat Cebesoy Bulv. No: 45, Gaziantep, Turkey. drmehmetceylan@hotmail.com. 2. Department of General Surgery, Faculty of Medicine, Sanko University, Gaziantep, Turkey. 3. Department of Pathology, Bakırköy Dr Sadi Konuk Health Application and Research Center, Istanbul, Turkey. 4. Laboratory of Nutrigenomics and Epidemiology, Department of Food Engineering, Izmir Institute of Thecnology, Izmir, Turkey. 5. Department of Otorhinolaryngology, Faculty of Medicine, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey. 6. Department of Anatomy, Faculty of Medicine, Beykent University, Istanbul, Turkey. 7. Department of Emergency Medicine, Faculty of Medicine, Biruni University, Istanbul, Turkey. 8. Department of Otorhinolaryngology, Faculty of Medicine, Sanko University, Incilipinar Mah. Ali Fuat Cebesoy Bulv. No: 45, Gaziantep, Turkey.
Abstract
OBJECTIVE: The aim of this study was to investigate the potential protective and therapeutic effects of milrinone, a specific phosphodiesterase (PDE) III inhibitor, on acoustic trauma-induced cochlear injury and apoptosis. METHODS: A total number of 30 healthy Wistar albino rats were evenly divided into five groups as follows: group 1 was assigned as control group; group 2 and 3 were assigned as low-dosage groups (0.25 mg/kg) in which milrinone was administered 1 h before acoustic trauma (AT) and 2 h after AT, respectively; group 4 and 5 were assigned as high-dosage groups (0.50 mg/kg) in which the drug was administered 1 h before AT and 2 h after AT, respectively. Except control group, all treatment groups received a single dosage of milrinone for 5 days. Distortion product otoacoustic emissions (DPOAE) measurements were recorded before AT as well as at second and fifth post-traumatic days. At the end of fifth day, all rats were sacrificed and the cochlea of the rats was removed for histopathological evaluation. In addition, the groups were compared in terms of apoptotic index via caspase-3 staining. RESULTS: In terms of signal-to-noise ratio (SNR), there was no statistically significant difference among the groups following AT (p > 0.05). After 5 days of milrinone treatment, the best SNR values were found in group 5, though all groups did not statistically differ (p > 0.05). In histopathological evaluation, vacuolization, inflammation, and edema scores in all treatment groups were statistically lower than those of the control group (p < 0.05). In group 2 and 4 where the drug was administered before AT, the inflammation and apoptosis index was lower than those of group 3 and 5 where the drug was administered after AT (p < 0.0001). CONCLUSION: We reveal that milrinone has a protective effect on cochlear damage in the experimental acoustic model of rats. This protective effect was more apparent following the pre-traumatic milrinone administration, and is associated with its effect on decreasing inflammation and apoptosis. Based on DPOAE measurements following AT, especially in the group 5 (high-dosage group), milrinone may also have a therapeutic effect.
OBJECTIVE: The aim of this study was to investigate the potential protective and therapeutic effects of milrinone, a specific phosphodiesterase (PDE) III inhibitor, on acoustic trauma-induced cochlear injury and apoptosis. METHODS: A total number of 30 healthy Wistar albino rats were evenly divided into five groups as follows: group 1 was assigned as control group; group 2 and 3 were assigned as low-dosage groups (0.25 mg/kg) in which milrinone was administered 1 h before acoustic trauma (AT) and 2 h after AT, respectively; group 4 and 5 were assigned as high-dosage groups (0.50 mg/kg) in which the drug was administered 1 h before AT and 2 h after AT, respectively. Except control group, all treatment groups received a single dosage of milrinone for 5 days. Distortion product otoacoustic emissions (DPOAE) measurements were recorded before AT as well as at second and fifth post-traumatic days. At the end of fifth day, all rats were sacrificed and the cochlea of the rats was removed for histopathological evaluation. In addition, the groups were compared in terms of apoptotic index via caspase-3 staining. RESULTS: In terms of signal-to-noise ratio (SNR), there was no statistically significant difference among the groups following AT (p > 0.05). After 5 days of milrinone treatment, the best SNR values were found in group 5, though all groups did not statistically differ (p > 0.05). In histopathological evaluation, vacuolization, inflammation, and edema scores in all treatment groups were statistically lower than those of the control group (p < 0.05). In group 2 and 4 where the drug was administered before AT, the inflammation and apoptosis index was lower than those of group 3 and 5 where the drug was administered after AT (p < 0.0001). CONCLUSION: We reveal that milrinone has a protective effect on cochlear damage in the experimental acoustic model of rats. This protective effect was more apparent following the pre-traumatic milrinone administration, and is associated with its effect on decreasing inflammation and apoptosis. Based on DPOAE measurements following AT, especially in the group 5 (high-dosage group), milrinone may also have a therapeutic effect.
Authors: S G Zhuravskii; L A Aleksandrova; S A Ivanov; V S Sirot; A I Lopotko; A A Zhloba Journal: Bull Exp Biol Med Date: 2004-01 Impact factor: 0.804
Authors: René Rissel; Moritz Gosling; Jens Kamuf; Miriam Renz; Robert Ruemmler; Alexander Ziebart; Erik K Hartmann Journal: Biomedicines Date: 2022-04-29