Skip to main content
SpringerLink
Log in

The Protective Role of Molsidomine on the Cisplatin-Induced Ototoxicity

  • Original Article
  • Published:
Indian Journal of Otolaryngology and Head & Neck Surgery Aims and scope Submit manuscript

Abstract

This experimental study was designed to investigate the protective effects of molsidomine (MOL) on against cisplatin-induced ototoxicity (CIO). To examine this effect, distortion product otoacoustic emissions (DPOAEs) measurements and serum levels of oxidative and antioxidant status [including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPX), total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI)] were evaluated. Thirty-two female wistar albino rats were divided into four groups including; control (Group K), cisplatin (Group C), cisplatin plus MOL group (Group CM), and MOL group (Group M). DPOAEs measurements between 0.9961 and 8.0003 Hz as DP-gram and input/output (I/O) functions were performed in the same (left) ear of all rats on days 0, 1st, 5th and 12th. Prior to death, the last DPOAEs measurements and blood samples were taken. In the C group, statistically significant DPOAE amplitude reductions were detected at 2.5195, 3.1758, 3.9961, 5.0391, 6.3516 and 8.0039 Hz frequencies (p < 0.05) between 0th and 1st, 0th and 5th and 0th and 12th days’ measurements (p < 0.05). Serum level of MDA, TAC and OSI levels were significantly higher in the C group versus K group (p < 0.05). In the CM group, there were no significant differences at all frequencies between 0th and other days’ measurements (p > 0.05) and the serum levels of all biochemical parameters were shifted toward normal values, similar to the K group (p < 0.05). No significant differences were detected in the either M or K group’s measurements. According to these results, cisplatin-related ototoxicity has been significantly prevented by MOL.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Rybak LP, Whitworth CA (2005) Ototoxicity: therapeutic opportunities. Drug Discovery Today 10:1313–1321

    Article  CAS  PubMed  Google Scholar 

  2. Rybak LP, Mukherjea D, Jajoo S, Ramkumar V (2009) Cisplatin ototoxicity and protection: clinical and experimental studies. Tohoku J Exp Med 219:177–186

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Altintas R, Parlakpinar H, Beytur A, Vardi N, Polat A, Sagir M, Odabas GP (2012) Protective effect of dexpanthenol on ischemia-reperfusion-induced renal injury in rats. Kidney Blood Press Res 36:220–230

    Article  CAS  PubMed  Google Scholar 

  4. Yumusakhuylu AC, Yazici M, Sari M, Binnetoglu A, Kosemihal E, Akdas F, Sirvanci S, Yuksel M, Uneri C, Tutkun A (2012) Protective role of resveratrol against cisplatin induced ototoxicity in guinea pigs. Int J Pediatr Otorhinolaryngol 76:404–408

    Article  PubMed  Google Scholar 

  5. Ravi R, Somani SM, Rybak LP (1995) Mechanism of cisplatin ototoxicity: antioxidant system. Pharmacol Toxicol 76:386–394

    Article  CAS  PubMed  Google Scholar 

  6. Erdem T, Bayindir T, Filiz A, Iraz M, Selimoglu E (2012) The effect of resveratrol on the prevention of cisplatin ototoxicity. Eur Arch Otorhinolaryngol 269:2185–2188

    Article  CAS  PubMed  Google Scholar 

  7. Celebi S, Gurdal MM, Ozkul MH, Yasar H, Balikci HH (2013) The effect of intratympanic vitamin C administration on cisplatin-induced ototoxicity. Eur Arch Otorhinolaryngol 270:1293–1297

    Article  PubMed  Google Scholar 

  8. Kalcioglu MT, Kizilay A, Gulec M, Karatas E, Iraz M, Akyol O, Egri M, Ozturan O (2005) The protective effect of erdosteine against ototoxicity induced by cisplatin in rats. Eur Arch Otorhinolaryngol 262:856–863

    Article  PubMed  Google Scholar 

  9. Kizilay A, Kalcioglu MT, Ozerol E, Iraz M, Gulec M, Akyol O, Ozturan O (2004) Caffeic acid phenethyl ester ameliorated ototoxicity induced by cisplatin in rats. J Chemother 16:381–387

    Article  CAS  PubMed  Google Scholar 

  10. Kelles M, Tan M, Kalcioglu MT, Toplu Y, Bulam N (2013) The protective effect of Chrysin against cisplatin induced ototoxicity in rats. Indian J Otolaryngol Head Neck Surg. doi:10.1007/s12070-013-0695-x

    PubMed  Google Scholar 

  11. Gruetter CA, Barry BK, McNamara DB et al (1979) Relaxation of bovine coronary artery and activation of coronary arterial guanylate cyclase by nitric oxide, nitroprusside and a carcinogenic nitrosoamine. J Cyclic Nucleotide Res 5:211–224

    CAS  PubMed  Google Scholar 

  12. Bentli R, Parlakpinar H, Polat A, Samdanci E, Sarihan ME, Sagir M (2013) Molsidomine prevents cisplatin-induced hepatotoxicity. Arch Med Res 4:521–528

    Article  Google Scholar 

  13. Disli OM, Sarihan E, Colak MC, Vardi N, Polat A, Yagmur J, Tamtekin B, Parlakpinar H (2013) Effects of molsidomine on doxorubicin-induced cardiotoxicity in rats. Eur Surg Res 51:79–90. doi:10.1159/000354807

    Article  CAS  PubMed  Google Scholar 

  14. Uchiyama M, Mihara M (1978) Determination of malonaldehyde precursor in tissues by tiobarbituric acid test. Anal Biochem 34:271–278

    Article  Google Scholar 

  15. Sun Y, Oberley L, Li Y (1988) A simple method for clinical assay of superoxide dismutase. Clin Chem 34:497–500

    CAS  PubMed  Google Scholar 

  16. Aebi H (1974) Catalase. In: Bergmeyer HU (ed) Methods of enzymatic analysis. Academic Press, New York, pp 673–677

    Chapter  Google Scholar 

  17. Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70:158–170

    CAS  PubMed  Google Scholar 

  18. Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77

    Article  CAS  PubMed  Google Scholar 

  19. Erel O (2004) A novel automated direct measurement method for total antioxidant capacitiy using a new generation, more stable ABTS radical cation. Clin Biochem 37:277–285

    Article  CAS  PubMed  Google Scholar 

  20. Erel O (2005) A new automated colorimetric method for measuring total oxidant status. Clin Biochem 38:1103–1111

    Article  CAS  PubMed  Google Scholar 

  21. Aycicek A, Erel O, Kocyigit A (2005) Decreased total antioxidant capacity and increased oxidative stress in passive smoker infants and their mothers. Pediatr Int 47:635–639

    Article  CAS  PubMed  Google Scholar 

  22. McKeage MJ (1995) Comparative adverse effects of platinum drugs. Drug Saf 13:228–244

    Article  CAS  PubMed  Google Scholar 

  23. Kukovetz WR, Holzmann S (1986) Cyclic GMP as the mediator of molsidomine-induced vasodilatation. Eur J Pharmacol 122:109–130

    Article  Google Scholar 

  24. Johnson G 3rd, Tsao PS, Lefer AM (1991) Cardioprotective effects of authentic nitric oxide in myocardial ischemia with reperfusion. Crit Care Med 19:244–252

    Article  PubMed  Google Scholar 

  25. Chander V, Chopra K (2005) Renal protective effect of molsidomine and l-arginine in ischemia–reperfusion induced injury in rats. J Surg Res 128:132–139

    Article  CAS  PubMed  Google Scholar 

  26. Rodriguez-Peña A, Garcia-Criado FJ, Eleno N et al (2004) Intrarenal administration of molsidomine, a molecule releasing nitric oxide, reduces renal ischemia–reperfusion injury in rats. Am J Transplant 4:1605–1613

    Article  PubMed  Google Scholar 

  27. Disli OM, Sarihan E, Colak MC, Vardi N, Polat A, Yagmur J, Tamtekin B, Parlakpinar H (2013) Effects of molsidomine against doxorubicin-induced cardiotoxicity in rats. Eur Surg Res 51:79–90

    Article  CAS  PubMed  Google Scholar 

  28. Lopez-Gonzalez MA, Guerrero JM, Rojas F, Delgado F (2000) Ototoxicity caused by cisplatin is ameliorated by melatonin and other antioxidants. J Pineal Res 28:73–80

    Article  CAS  PubMed  Google Scholar 

  29. Ozturan O, Jerger J, Lew H, Lynch GR (1996) Monitoring of cisplatin ototoxicity by distortion-product otoacoustic emissions. Auris Nasus Larynx 23:147–151

    Article  CAS  PubMed  Google Scholar 

  30. Rybak LP, Whitworth CA, Mukherjea D, Ramkuvar V (2007) Mechanisms of cisplatin-induced ototoxicity and prevention. Hear Res 226:157–167

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

None declared.

Author information

Authors and Affiliations

  1. Department of Otorhinolaryngology, Medical Faculty, Inonu University, Malatya, Turkey

    Yuksel Toplu, Erkan Karatas & Ahmet Kizilay

  2. Pharmacology Department, Medical Faculty, Inonu University, Malatya, Turkey

    Hakan Parlakpinar

  3. Department of Otorhinolaryngology, Malatya State Hospital, Malatya, Turkey

    Emrah Sapmaz

  4. Physiology Department, Medical Faculty, Inonu University, Malatya, Turkey

    Alaattin Polat

Authors
  1. Yuksel Toplu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hakan Parlakpinar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Emrah Sapmaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Erkan Karatas
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alaattin Polat
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ahmet Kizilay
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yuksel Toplu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Toplu, Y., Parlakpinar, H., Sapmaz, E. et al. The Protective Role of Molsidomine on the Cisplatin-Induced Ototoxicity. Indian J Otolaryngol Head Neck Surg 66, 314–319 (2014). https://doi.org/10.1007/s12070-014-0718-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12070-014-0718-2

Keywords

Search

Navigation