Abstract
Purpose: The aim of this study was to evaluate the efficacy of adrenomedullin on damage associated with cisplatin ototoxicity created in an experimental animal model.
Materials and Methods: A total of 32 Wistar Albino rats were separated into 4 groups of 8. To the rats in Group 1 (control), 1% acetic acid was administered intraperitoneally and intratympanically, to Group 2, cisplatin (10mg/kg/2 days) + intratympanic acetic acid, to Group 3, cisplatin + intraperitoneal adrenomedullin (12 µg/kg) and to Group 4, cisplatin +0.1- 0.3ml intratympanic adrenomedullin (12 µg/kg). The drugs were administered on the first 5 days and signal-to-noise ratio (SNR) measurements of the auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) were made on days 0, 5 and 15. The rats were sacrificed and serum and ear tissue samples were taken for histopathological examination and examination of oxidative stress levels.
Results: A statistically significant difference was determined in the cisplatin+intratympanic adrenomedullin group in the Auditory brain-stem response (ABR) measurements on days 0, 5 and 15 . In the Distortion product-evoked otoacoustic emission (DPOAE) measurements, the between-day differences at 16000 frequency in the cisplatin + intraperitoneal adrenomedullin group were accepted as statistically significant
Conclusion: Adrenomedullin, which is a strong vasodilator and antioxidant, was found to have a protective effect against cisplatin ototoxicity in the cochlea.
References
- 1. Rabik CA, Dolan ME, Molecular mechanisms of resistance and toxicity associated with platinating agents, Cancer Treat Rev. 2007;33: 9–23.2. Daldal A, Odabasi O, Serbetcioglu B, The protective effect of intratympanic dexamethasone on cisplatin-induced ototoxicity in guinea pigs, Otolaryngol Head Neck Surg.2007;137 :747-52.3. Sockalingam R, Freeman S, Cherny TL, Sohmer H, Effect of high-dose cisplatin on auditory brainstem responses and otoacoustic emissions in laboratory animals, Am J Otol 2000;21 :521–27.4. Kirisci M, Oktar GL, Ozogul C, Oyar EO, Akyol SN, Demirtas CY, Arslan M, Effect of adrenomedullin and vascular endothelial growth factor on ischemia/reperfusion injury in sceletal muscle in rats, J Surg Res. 2013;185: 56-63.5. Wimalawansa SJ, Amylin calcitonin gene-related peptide, calcitonin, and adrenomedullin: a peptide superfamily, Crit Rev Neurobiol 1997;11: 167–239. 6. Hinson JP, Kapas S, Smith DM, Adrenomedullin, a multifunctional regulatory peptide, Endocr Rev. 2000;21: 138– 67. 7. Nishikimi T, Kitamura K, Saito Y, Shimada K, Ishimitsu T, Takamiya M, Kangawa K, Matsuo H, Eto T, Omae T, Clinical studies on the sites of production and clearance of circulating adrenomedullin in human subjects, Hypertension. 1994;24: 600–4.8. de Freitas MR, de Castro Brito GA, de Carvalho JV Jr, Gomes RM Jr, Barreto Martins MJ, de Albuquerque Ribeiro R, Light microscopy study of cisplatin-induced ototoxicity in rats, J Laryngol Otol. 2009;123: 590–79. Fridovich I, Superoxide dismutase, Adv Enzymol. 1974;41:35-97.10. Beutler E, Red Cell Metabolism: A Manual of Biochemical Methods, 3rd edn., New York, Grune and Stratton Inc, 1984.11. Ohkawa H, Ohishi N, Tagi K, Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction, Anal Biochem. 1979;95: 351-8.12. Yoshimoto T, Fukai N, Sato R, Sugiyama T, Ozawa N, Shichiri M, Hirata Y, Antioxidant effect of adrenomedullin on angiotensin II-induced reactive oxygenspecies generation in vascular smooth muscle cells, Endocrinology. 2004; 145: 3331-7. 13. Shimosawa T, Shibagaki Y, Ishibashi K, Kitamura K, Kangawa K, Kato S, Ando K, Fujita T, Adrenomedullin, an endogenous peptide, counteracts cardiovascular damage, Circulation. 2002;105: 106.14. Bekmez Bilmez ZE, Aydin S, Sanli A, Altintoprak N, Demir MG, Atalay Erdoğan B, Kösemihal E, Oxytocin as a protective agent in cisplatin-induced ototoxicity, Cancer Chemother Pharmacol. 2016; 77: 875-9.15. Yumusakhuylu AC, Yazici M, Sari M, Binnetoglu A, Kosemihal E, Akdas F, Sirvanci S, Yüksel M, Uneri C, Tutkun A, Protective role of resveratrol against cisplatin induced ototoxicity in guinea pigs, Int J Pediatr Otorhinolaryngol. 2012;76: 404-8.16. Toplu Y, Sapmaz E, Parlakpinar H, Kelles M, Kalcioglu MT, Tanbek K, Kizilay A, The effect of dexpanthenol on ototoxicity induced by cisplatin, Clin Exp Otorhinolaryngol. 2016; 9: 14-20.17. Shafik AG, Elkabarity RH, Thabet MT, Soliman NB, Kalleny NK, Effect of intratympanic dexamethasone administration on cisplatin induced ototoxicity in adult guinea pigs, Auris Nasus Larynx. 2013;40: 51-60.18. Kara M, Turkon H, Karaca T, Guclu O,Uysal S, Turkyilmaz M, Demirtaş S,Derekoy FS, Evaluation of the protective effects of hesperetin against cisplatin- induced ototoxicity in a rat animal model, Int J Pediatr Otorhinolaryngol. 2016;85:12- 8.19. Ozkırıs M, Kapusuz Z, Karacavus S, Saydam L, The effects of lycopene on cisplatin-induced ototoxicity, Int J Pediatr Otorhinolaryngol. 2013;270: 3027- 33.20. Demir MG, Altıntoprak N, Aydin S, Kösemihal E, Basak K, Effect of transtympanic injection of melatonin on cisplatin- induced Ototoxicity, J Int Adv Otol. 11 (2015) 202-6.21. Rybak LP, Husain K, Morris C, Whitworth C, Somani S, Effect of protective agents against cisplatin ototoxicity, Am J Otol. 2000;21: 513–20.22. Clerici WJ, Hensley K, Dimartino DL, Butterfield DA, Direct detection of ototoxicant-induced reactive oxygen species generation in cochlear explants, Hear Res. 1996;98: 116-24.23. Labbé D, Teranishi MA, Hess A, Bloch W, Michel O, Activation of caspase-3 is associated with oxidative stress in the hydropic guinea pig cochlea, Hear Res. 2005;202: 21-7.24. Huang T, Cheng AG, Stupak H, Liu W, Kim A, Staecker H, Levebvre PP, Malqrenqe B, Kopke R, Moonen G, Van De Water TR, Oxi¬dative stress-induced apoptosis of cochlear sensory cells: otoprotec¬tive strategies, Int J Dev Neurosci. 2000;18: 259-70.25. Mates JM, Perez-Gomez C, Nunez de Castro I, Antioxidant enzymes and human diseases, Clin Biochem. 1999;32: 595–603.26. Pugliese PT, The skin’s antioxidant systems, Dermatol Nurs. 1998;10: 401–16.27. Maccarrone M, Catani MV, Iraci S, Melino G, Agro AF, A survey of reactive oxygen species and their role in dermatology, J Eur Acad Dermatol Venereol. 1997;8:185–202.28. Kang HK, Kim DK, Lee BH, Om AS, Hong JH, Koh HC, Lee CH, Shin IC, Kang JS, Urinary N-acetyl-beta- D-glucosaminidase and malondialdehyde as a markers of renal damage in burned patients, J Korean Med Sci. 2001;16: 598–602.29. Etoz BC, Buyukcoskun Nİ, Adrenomedullin ve etkileri, Uludag Tıp Derg 2005;32: 127-132 (article in Turkish)
Abstract
Amaç: Bu çalışmanın amacı daha önce hiç çalışılmamış olan adrenomedüllinin deneysel hayvan modelinde oluşturulan cisplatin ototoksisitesine bağlı hasarı üzerindeki etkinliğini değerlendirmektir.
Gereç ve Yöntem: 32 wistar albino rat 4 gruba ayrıldı. Grup 1 kontrol grubu intraperitoneal ve intratimpanik %1 asedik asit verilen, grup 2 cisplatin (10 mg/kg/ 2 gün)+ intratimpanik asedik asit verilen, grup 3 cisplatin + intraperitoneal adrenomedüllin (12mikrogr/kg) verilen, grup 4 cisplatin + 0,1-0,3 ml intratimpanik (12mikrogr/kg) adrenomedüllin verilen grup olarak her bir grupta rastgele 8 rat olacak şekilde düzenlendi. İlk 5 gün ilaç uygulamaları yapıldı. ABR ve DPOAE deki sinyal gürültü oranları (SNR) 0. 5. ve 15. gün ölçümleri yapıldı. Ratlar sakrifiye edildi, histopatolojik inceleme, serum ve kulak doku örneklerinde oksidatif stres düzeyleri çalışıldı.
Bulgular: İşitsel uyarılmış beyinsapı potansiyelleri (ABR) ölçümlerinde C+IT ADM grubunun 0. gün 5. gün ve 15. gün değerleri arasındaki farklılık istatistiksel olarak anlamlı olarak değerlendirilmiştir. Distorsiyon ürünü otoakustik emisyon (DPOAE) ölçümlerine göre 16000 hz frekanstaki cisplatin + intraperitoneal adrenomedüllin grubundaki günler arasındaki farklılık istatistiksel olarak anlamlı olarak kabul edilmiştir
Sonuç: Güçlü bir vazodilatattör ve antioksidan olan adrenomedüllinin cisplatin ototoksisistesinde kokleayı koruyucu etkisinin olduğu bulundu.
Keywords
References
- 1. Rabik CA, Dolan ME, Molecular mechanisms of resistance and toxicity associated with platinating agents, Cancer Treat Rev. 2007;33: 9–23.2. Daldal A, Odabasi O, Serbetcioglu B, The protective effect of intratympanic dexamethasone on cisplatin-induced ototoxicity in guinea pigs, Otolaryngol Head Neck Surg.2007;137 :747-52.3. Sockalingam R, Freeman S, Cherny TL, Sohmer H, Effect of high-dose cisplatin on auditory brainstem responses and otoacoustic emissions in laboratory animals, Am J Otol 2000;21 :521–27.4. Kirisci M, Oktar GL, Ozogul C, Oyar EO, Akyol SN, Demirtas CY, Arslan M, Effect of adrenomedullin and vascular endothelial growth factor on ischemia/reperfusion injury in sceletal muscle in rats, J Surg Res. 2013;185: 56-63.5. Wimalawansa SJ, Amylin calcitonin gene-related peptide, calcitonin, and adrenomedullin: a peptide superfamily, Crit Rev Neurobiol 1997;11: 167–239. 6. Hinson JP, Kapas S, Smith DM, Adrenomedullin, a multifunctional regulatory peptide, Endocr Rev. 2000;21: 138– 67. 7. Nishikimi T, Kitamura K, Saito Y, Shimada K, Ishimitsu T, Takamiya M, Kangawa K, Matsuo H, Eto T, Omae T, Clinical studies on the sites of production and clearance of circulating adrenomedullin in human subjects, Hypertension. 1994;24: 600–4.8. de Freitas MR, de Castro Brito GA, de Carvalho JV Jr, Gomes RM Jr, Barreto Martins MJ, de Albuquerque Ribeiro R, Light microscopy study of cisplatin-induced ototoxicity in rats, J Laryngol Otol. 2009;123: 590–79. Fridovich I, Superoxide dismutase, Adv Enzymol. 1974;41:35-97.10. Beutler E, Red Cell Metabolism: A Manual of Biochemical Methods, 3rd edn., New York, Grune and Stratton Inc, 1984.11. Ohkawa H, Ohishi N, Tagi K, Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction, Anal Biochem. 1979;95: 351-8.12. Yoshimoto T, Fukai N, Sato R, Sugiyama T, Ozawa N, Shichiri M, Hirata Y, Antioxidant effect of adrenomedullin on angiotensin II-induced reactive oxygenspecies generation in vascular smooth muscle cells, Endocrinology. 2004; 145: 3331-7. 13. Shimosawa T, Shibagaki Y, Ishibashi K, Kitamura K, Kangawa K, Kato S, Ando K, Fujita T, Adrenomedullin, an endogenous peptide, counteracts cardiovascular damage, Circulation. 2002;105: 106.14. Bekmez Bilmez ZE, Aydin S, Sanli A, Altintoprak N, Demir MG, Atalay Erdoğan B, Kösemihal E, Oxytocin as a protective agent in cisplatin-induced ototoxicity, Cancer Chemother Pharmacol. 2016; 77: 875-9.15. Yumusakhuylu AC, Yazici M, Sari M, Binnetoglu A, Kosemihal E, Akdas F, Sirvanci S, Yüksel M, Uneri C, Tutkun A, Protective role of resveratrol against cisplatin induced ototoxicity in guinea pigs, Int J Pediatr Otorhinolaryngol. 2012;76: 404-8.16. Toplu Y, Sapmaz E, Parlakpinar H, Kelles M, Kalcioglu MT, Tanbek K, Kizilay A, The effect of dexpanthenol on ototoxicity induced by cisplatin, Clin Exp Otorhinolaryngol. 2016; 9: 14-20.17. Shafik AG, Elkabarity RH, Thabet MT, Soliman NB, Kalleny NK, Effect of intratympanic dexamethasone administration on cisplatin induced ototoxicity in adult guinea pigs, Auris Nasus Larynx. 2013;40: 51-60.18. Kara M, Turkon H, Karaca T, Guclu O,Uysal S, Turkyilmaz M, Demirtaş S,Derekoy FS, Evaluation of the protective effects of hesperetin against cisplatin- induced ototoxicity in a rat animal model, Int J Pediatr Otorhinolaryngol. 2016;85:12- 8.19. Ozkırıs M, Kapusuz Z, Karacavus S, Saydam L, The effects of lycopene on cisplatin-induced ototoxicity, Int J Pediatr Otorhinolaryngol. 2013;270: 3027- 33.20. Demir MG, Altıntoprak N, Aydin S, Kösemihal E, Basak K, Effect of transtympanic injection of melatonin on cisplatin- induced Ototoxicity, J Int Adv Otol. 11 (2015) 202-6.21. Rybak LP, Husain K, Morris C, Whitworth C, Somani S, Effect of protective agents against cisplatin ototoxicity, Am J Otol. 2000;21: 513–20.22. Clerici WJ, Hensley K, Dimartino DL, Butterfield DA, Direct detection of ototoxicant-induced reactive oxygen species generation in cochlear explants, Hear Res. 1996;98: 116-24.23. Labbé D, Teranishi MA, Hess A, Bloch W, Michel O, Activation of caspase-3 is associated with oxidative stress in the hydropic guinea pig cochlea, Hear Res. 2005;202: 21-7.24. Huang T, Cheng AG, Stupak H, Liu W, Kim A, Staecker H, Levebvre PP, Malqrenqe B, Kopke R, Moonen G, Van De Water TR, Oxi¬dative stress-induced apoptosis of cochlear sensory cells: otoprotec¬tive strategies, Int J Dev Neurosci. 2000;18: 259-70.25. Mates JM, Perez-Gomez C, Nunez de Castro I, Antioxidant enzymes and human diseases, Clin Biochem. 1999;32: 595–603.26. Pugliese PT, The skin’s antioxidant systems, Dermatol Nurs. 1998;10: 401–16.27. Maccarrone M, Catani MV, Iraci S, Melino G, Agro AF, A survey of reactive oxygen species and their role in dermatology, J Eur Acad Dermatol Venereol. 1997;8:185–202.28. Kang HK, Kim DK, Lee BH, Om AS, Hong JH, Koh HC, Lee CH, Shin IC, Kang JS, Urinary N-acetyl-beta- D-glucosaminidase and malondialdehyde as a markers of renal damage in burned patients, J Korean Med Sci. 2001;16: 598–602.29. Etoz BC, Buyukcoskun Nİ, Adrenomedullin ve etkileri, Uludag Tıp Derg 2005;32: 127-132 (article in Turkish)
Details
| Primary Language | English |
|---|---|
| Subjects | Clinical Sciences |
| Journal Section | Research |
| Authors | |
| Publication Date | June 30, 2019 |
| Acceptance Date | November 29, 2018 |
| Published in Issue | Year 2019 Volume: 44 Issue: 2 |
