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Protective and therapeutic effects of milrinone on acoustic trauma in rat cochlea
Seyit Mehmet Ceylan1, Erdal Uysal2, Serdar Altinay3
1Department of Otorhinolaryngology, Faculty of Medicine, Sanko University, Incilipinar Mah. Ali Fuat Cebesoy Bulv. No: 45, Gaziantep, Turkey. drmehmetceylan@hotmail.com.
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.
Insights
Milrinone, a phosphodiesterase (PDE) III inhibitor, shows protective effects against acoustic trauma-induced cochlear injury in rats. Pre-traumatic administration was more effective in reducing inflammation and apoptosis.
Area of Science:
- Ototoxicology
- Pharmacology
- Cellular Biology
Background:
- Acoustic trauma (AT) can cause significant cochlear damage and apoptosis.
- Phosphodiesterase (PDE) III inhibitors, like milrinone, are being investigated for potential protective effects.
- Understanding the role of milrinone in mitigating AT-induced cochlear injury is crucial for developing new therapeutic strategies.
Purpose of the Study:
- To investigate the protective and therapeutic effects of milrinone on cochlear injury and apoptosis induced by acoustic trauma.
- To evaluate the impact of milrinone dosage and administration timing (pre- vs. post-trauma) on these effects.
Main Methods:
- Wistar albino rats were divided into five groups: control, low-dose (0.25 mg/kg) milrinone before/after AT, and high-dose (0.50 mg/kg) milrinone before/after AT.
- Distortion product otoacoustic emissions (DPOAE) were measured before and after AT.
- Histopathological evaluation and caspase-3 staining were performed to assess cochlear damage, inflammation, and apoptosis.
Main Results:
- Milrinone treatment significantly reduced vacuolization, inflammation, and edema scores compared to the control group.
- Pre-traumatic administration of milrinone (groups 2 and 4) resulted in lower inflammation and apoptosis indices than post-traumatic administration (groups 3 and 5).
- While signal-to-noise ratio (SNR) did not show statistically significant differences, the high-dose, pre-traumatic group exhibited the best SNR values.
Conclusions:
- Milrinone demonstrates a protective effect against acoustic trauma-induced cochlear damage in rats.
- Pre-traumatic administration of milrinone enhances its protective effect by reducing inflammation and apoptosis.
- Milrinone may also possess therapeutic potential for acoustic trauma, particularly at higher doses and when administered before injury.
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