Top

European Archives of Oto-Rhino-Laryngology

Published in:

01-07-2019 | Acoustic Trauma | Otology

Protective and therapeutic effects of milrinone on acoustic trauma in rat cochlea

Authors: Seyit Mehmet Ceylan, Erdal Uysal, Serdar Altinay, Efe Sezgin, Nagihan Bilal, Emine Petekkaya, Mehmet Dokur, Mahmut Alper Kanmaz, Mustafa Emre Gulbagci

Published in: European Archives of Oto-Rhino-Laryngology | Issue 7/2019

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.

Basner M, Babisch W, Davis A, Brink M, Clark C, Janssen S, Stansfeld S (2014) Auditory and non-auditory effects of noise on health. Lancet 383:1325–1332CrossRefPubMed

Zhang J, Song YL, Tian KY, Qiu JH (2017) Minocycline attenuates noise-induced hearing loss in rats. Neurosci Lett 639:31–35CrossRefPubMed

Ogurlu M, Celebi Erdivanli O, Tumkaya L, Ozgur A, Ozergin Coskun Z, Terzi S, Demirci M, Dursun E (2017) The therapeutic effect of thymoquinone on acoustic trauma-induced hearing loss in rats. Eur Arch Otorhinolaryngol 274(2):743–749CrossRefPubMed

Motalebi Kashani M, Saberi H, Hannani M (2013) Prevention of acoustic trauma-induced hearing loss by N-acetylcysteine administration in rabbits. Arch Trauma Res 1:145–150CrossRefPubMedPubMedCentral

Fetoni AR, Ralli M, Sergi B, Parrilla C, Troiani D, Paludetti G (2009) Protective effects of N-acetylcysteine on noise-induced hearing loss in guinea pigs. Acta Otorhinolaryngol Ital 29:70Y5

Gumrukcu SS, Topaloglu İ, Salturk Z, Tutar B, Atar Y, Berkiten G, Göker AE (2018) Effects of intratympanic dexamethasone on noise-induced hearing loss: an experimental study. Am J Otolaryngol 39(1):71–73CrossRefPubMed

Lorito G, Giordano P, Petruccelli J, Martini A, Hatzopoulos S (2008) Different strategies in treating noiseinduced hearing loss with N-acetylcysteine. Med Sci Monit 14(8):159–164

Sakat MS, Kilic K, Bercin S (2016) Pharmacological agents used for treatment and prevention in noise-induced hearing loss. Eur Arch Otorhinolaryngol 273:4089–4101CrossRefPubMed

Kansu L, Ozkarakas H, Efendi H, Okar I (2011) Protective effects of pentoxifylline and nimodipine on acoustic trauma in guinea pig cochlea. Otol Neurotol 32:919–925CrossRefPubMed

10.

Boswell-Smith V, Spina D, Page CP (2006) Phosphodiesterase inhibitors. Br J Pharmacol 147:252–257CrossRef

11.

Jung HS, Joo JD, Kim DW et al (2014) Effect of milrinone on the inflammatory response and NF-kB activation in renal ischemia-reperfusion injury in mice. Korean J Anesthesiol 66:136–142CrossRefPubMedPubMedCentral

12.

Besirli K, Burhani SM, Arslan C et al (2006) Effect of combining phosphodiesterase III inhibitors with St Thomas Hospital’s solution used as transplantation preservative solution in isolated rat hearts. Transplant Proc 38:1253–1258CrossRefPubMed

13.

Zhang J, Chen F, Zhao X et al (2009) Nebulized phosphodiesterase III inhibitor during warm ischemia attenuates pulmonary ischemia-reperfusion injury. J Heart Lung Transplant 28:79–84CrossRefPubMed

14.

Satoh K, Kume M, Abe Y et al (2009) Implication of protein kinase A for a hepato-protective mechanism of milrinone pretreatment. J Surg Res 155:32–39CrossRefPubMed

15.

Nishiki T, Kitada H, Okabe Y, Miura Y, Kurihara K, Kawanami S, Tanaka M (2011) Effect of milrinone on ischemia-reperfusion injury in the rat kidney. Transplant Proc 43:1489–1494CrossRefPubMed

16.

Uysal E, Dokur M, Altınay S, Saygılı Eİ, Batcıoglu K, Ceylan MS, Kazımoglu H, Uyumlu BA, Karadag M (2017) Investigation of the effect of milrinone on renal damage in an experimental non-heart beating donor model. J Investig Surg 14:1–10

17.

Lanfear DE, Hasan R, Gupta RC et al (2009) Short term effects of milrinone on biomarkers of necrosis, apoptosis, and inflammation in patients with severe heart failure. J Transl Med 7:67CrossRefPubMedPubMedCentral

18.

White M, Ducharme A, Ibrahim R et al (2006) Increased systemic inflammation and oxidative stress in patients with worsening congestive heart failure: improvement after short-term inotropic support. Clin Sci (Lond) 110(4):483–489CrossRef

19.

Miranda ML, Pereira SJ, Santos AOMT, Villela NR, Kraemer-Aguiar LG, Bouskela E (2015) Milrinone attenuates arteriolar vasoconstriction and capillary perfusion deficits on endotoxemic hamsters. PLoS One 10(2):e0117004CrossRefPubMedPubMedCentral

20.

Saklani R, Jaggi A, Singh N (2010) Pharmacological preconditioning by milrinone: memory preserving and neuroprotective effect in ischemia-reperfusion injury in mice. Arch Pharm Res 33(7):1049–1057CrossRefPubMed

21.

Han X, Ge R, Xie G, Li P, Zhao X, Gao L, Zhang H, Wang O, Huang F, Han F (2015) Caspase-mediated apoptosis in the cochleae contributes to the early onset of hearing loss in A/J mice. ASN Neuro 7(1):1–13CrossRef

22.

Boettcher FA, Caldwell RK, Gratton MA, White DR, Miles LR (1998) Effects of nimodipine on noise-induced hearing loss. Hear Res 121:139Y46CrossRef

23.

Lamm K, Arnold W (1996) Noise-induced cochlear hypoxia is intensity dependent, correlates with hearing loss and precedes reduction of cochlear blood flow. Audiol Neurootol 1(3):148–160CrossRefPubMed

24.

Dogan R, Sjostrand AP, Yenıgun A, Karatas E, Kocyigit A, Ozturan O (2018) Influence of Ginkgo Biloba extract (EGb 761) on expression of IL-1 Beta, IL-6, TNF-alfa, HSP-70, HSF-1 and COX-2 after noise exposure in the rat cochlea. Auris Nasus Larynx 45(4):680–685CrossRefPubMed

25.

Sendowski I (2006) Magnesium therapy in acoustic trauma. Magnes Res 19(4):244–254PubMed

26.

Lamm K, Arnold W (1999) Successful treatment of noise-induced cochlear ischemia, hypoxia, and hearing loss. Ann N Y Acad Sci 884:233–248CrossRefPubMed

27.

Lamm K, Arnold W (2000) The effect of blood flow promoting drugs on cochlear blood flow, perilymphatic pO₂ and auditory function in the normal and noise-damaged hypoxic and ischemic guinea pig inner ear. Hear Res 141:199–219CrossRefPubMed

28.

Anderson JL, Baim DS, Fein SA, Goldstein RA, Lejemtel TH, Likoff MJ (1987) Efficacy and safety of sustained (48 hour) intravenous infusion of milrinone in patients with severe congestive heart failure. A multicenter study. J Am Coll Cardiol 9:711–722CrossRefPubMed

29.

Arslan HH, Satar B, Serdar MA, Ozler M, Yilmaz E (2012) Effects of hyperbaric oxygen and dexamethasone on proinflammatory cytokines of rat cochlea in noise-induced hearing loss. Otol Neurotol 33(9):1672–1678CrossRefPubMed

30.

Kume M, Banafsche R, Yamamoto Y, Yamaoka Y, Nobiling R et al (2006) Dynamic changes of postischemic hepatic microcirculation improved by a pre-treatment of phosphodiesterase-3 inhibitor, milrinone. J Surg Res 136:209–218CrossRefPubMed

31.

Hayashida N, Tomoeda H, Oda T, Tayama E, Chihara S, Kawara T et al (1999) Inhibitory effect of milrinone on cytokine production after cardiopulmonary bypass. Ann Thorac Surg 68:1661–1667CrossRefPubMed

32.

Honkura Y, Matsuo H, Murakami S et al (2016) NRF2 is a key target for prevention of noise-induced hearing loss by reducing oxidative damage of cochlea. Sci Rep 6:19329CrossRefPubMedPubMedCentral

33.

Kamogashira T, Fujimoto C, Yamasoba T (2015) Reactive oxygen species, apoptosis, and mitochondrial dysfunction in hearing loss. Biomed Res Int 2015:617207CrossRefPubMedPubMedCentral

34.

Yamashita D, Shiotani A, Kanzaki S, Nakagawa M, Ogawa K (2008) Neuroprotective effects of T-817MA against noise-induced hearing loss. Neurosci Res 61(1):38–42CrossRefPubMed

35.

Fetoni AR, Paciello F, Rolesi R, Eramo SL, Mancuso C, Troiani D, Paludetti G (2015) Rosmarinic acid up-regulates the noise-activated Nrf2/HO-1 pathway and protects against noise-induced injury in rat cochlea. Free Radic Biol Med 85:269–281CrossRefPubMed

36.

Kobayashi T, Sugawara Y, Ohkubo T, Imamura H, Makuuchi M (2002) Effects of amrinone on hepatic ischemiareperfusion injury in rats. J Hepatol 37:31–38CrossRefPubMed

37.

Kucuk C, Akcan A, Akyildiz H, Akgun H, Muhtaroglu S, Sozuer E (2009) Effects of amrinone in an experimental model of hepatic ischemia-reperfusion injury. J Surg Res 151:74–79CrossRefPubMed

38.

Yoon SY, Eum JH, Cha SK, Yoon TK, Lee DR, Lee WS (2018) Prematuration culture with phosphodiesterase inhibitors after vitrification may induce recovery of mitochondrial activity in vitrified mouse immature oocytes. Biopreserv Biobank 16(4):296–303CrossRefPubMed

39.

Wang J, Tymczyszyn N, Yu Z, Yin S, Bance M, Robertson GS (2011) Overexpression of X-linked inhibitor of apoptosis protein protects against noise-induced hearing loss in mice. Gene Ther 18(6):560–568CrossRefPubMed

40.

Zhu WH, Majluf-Ctuz A, Omburo GA (1998) Cyclic AMP specific phosphodiesterase inhibitor rolipramandRo-20-1724 promoted apoptosis in HL 60 promyelocytic leukemic cells via cyclic AMP-independent mechanism. Life Sci 63:265–274CrossRefPubMed

41.

Jafari A, Baghaei A, Solgi R, Baeeri M, Chamanara M, Hassani S, Gholami M, Ostad SN, Sharifzadeh M, Abdollahi M (2015) An electrocardiographic, molecular and biochemical approach to explore the cardioprotective effect of vasopressin and milrinone against phosphide toxicity in rats. Food Chem Toxicol 80:182–192CrossRefPubMed

42.

Morrill S, He DZZ (2017) Apoptosis in inner ear sensory hair cells. J Otol 12:151e164

43.

Schmutzhard J, Glueckert R, Pritz C et al (2013) Sepsis otopathy: experimental sepsis leads to significant hearing impairment due to apoptosis and glutamate excitotoxicity in murine cochlea. Dis Model Mech 6:745–754CrossRefPubMedPubMedCentral

44.

Yanpallewar SU, Hota D, Rai S, Kumar M, Acharya SB (2004) Nimodipine attenuates biochemical, behavioral and histopathological alterations induced by acute transientand long-term bilateral common carotid occlusion in rats. Pharmacol Res 49:143–150CrossRefPubMed

45.

Iwasaki K, Egashira N, Takagaki Y, Yoshimitsu Y, Hatip-Al-Khatib I, Mishima K, Fujiwara M (2007) Nilvadipine prevents the impairment of spatial memory induced by cerebral ischemia combined with beta-amyloid in rats. Biol Pharm Bull 30:698–701CrossRefPubMed

46.

Wesley MC, McGowan FX, Castro RA, Dissanayake S, Zurakowski D, DiNardo JA (2009) The effect of milrinone on platelet activation as determined by TEG® Platelet Mapping™. Anesth Analg 108:1425–1429CrossRefPubMed

47.

Mariscalco MM (2006) Unlocking (perhaps unblocking) the microcirculation in sepsis. Crit Care Med 34:561–562CrossRefPubMed

48.

Murashita H, Tabuchi K, Hoshino T, Tsuji S, Hara A (2006) The effects of tempol, 3-aminobenzamide and nitric oxide synthase inhibitors on acoustic injury of the mouse cochlea. Hear Res 214:1–6CrossRefPubMed

49.

Zhuravskii SG, Aleksandrova LA, Ivanov SA, Sirot VS, Lopotko AI, Zhloba AA (2004) Protective effect of carnosine on excitable structures of the auditory apparatus in albino rats with acute acoustic trauma. Bull Exp Biol Med 137:98–102CrossRefPubMed

50.

Fetoni AR, Ferraresi A, Greca CL, Rizzo D, Sergi B, Tringali G et al (2008) Antioxidant protection against acoustic trauma by coadministration of idebenone and vitamin E. Neuroreport 19(3):277–281CrossRefPubMed

51.

Lopes AC, Otowiz VG, de Barros Lopes PM, Lauris JRP, Santos CC (2012) Prevalence of noise-induced hearing loss in drivers. Int Arch Otorhinolaryngol 16:509–514PubMedPubMedCentral

52.

Desjardins S, Cauchy MJ (1989) Acute effects of milrinone on the electrocardiogram and the cardiac hemodynamics of rats with pressure overload-induced congestive heart failure. Arch Int Pharmacodyn Ther 301:182–199PubMed

53.

Baruch L, Patacsil P, Hameed A, Pina I, Loh E (2001) Pharmacodynamic effects of milrinone with and without a bolus loading infusion. Am Heart J 141:266–267CrossRefPubMed

Title: Protective and therapeutic effects of milrinone on acoustic trauma in rat cochlea
Authors: Seyit Mehmet Ceylan
Erdal Uysal
Serdar Altinay
Efe Sezgin
Nagihan Bilal
Emine Petekkaya
Mehmet Dokur
Mahmut Alper Kanmaz
Mustafa Emre Gulbagci
Publication date: 01-07-2019
Publisher: Springer Berlin Heidelberg
Keywords: Acoustic Trauma
Milrinone
Published in: European Archives of Oto-Rhino-Laryngology / Issue 7/2019
Print ISSN: 0937-4477
Electronic ISSN: 1434-4726
DOI: https://doi.org/10.1007/s00405-019-05417-5

At a glance: The STEP trials

Springer Medicine

Protective and therapeutic effects of milrinone on acoustic trauma in rat cochlea

Abstract

Objective

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Objective

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 7/2019

Bilateral vocal fold injection with autologous fat in patients with vocal fold atrophy with or without sulcus

Two-handed tying technique in vocal fold mucosa microsuture for the treatment of Reinke’s edema

Imaging re-evaluation of the tympanic segment of the facial nerve canal using cone-beam computed tomography compared with multi-slice computed tomography

Predictive factors for late cervical metastasis in stage I and II squamous cell carcinoma of the lip

Response to: Oral cancer of Sigmund Freud

The diagnosis and treatment of a variant type of auricular sinus: postauricular sinus