Skip to main content

Advertisement

Log in

Oxytocin as a protective agent in cisplatin-induced ototoxicity

  • Short Communication
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Cisplatin is a potent chemotherapeutic drug with serious side effects such as ototoxicity which is characterized by irreversible, bilateral, progressive sensorineural hearing loss. Oxytocin, which is a well-known hormone secreting during pregnancy, has antioxidant and antiinflammatory effect. Our study aims to test and compare the effect of intratympanic (IT) and intraperitoneal (IP) oxytocin on cisplatin ototoxicity with DPOAE.

Methods

A total of 24 Wistar albino rats were randomly divided into four groups: Group 1 received 0.1–0.3 ml IT saline + IP saline solutions for 4 days (n = 6), Group 2 received cumulative dose of 20 mg/kg IP cisplatin divided into two equal doses in first and second days of experiment + 0.1–0.3 ml IT saline for 4 days, Group 3 received same dose of cisplatin as Group 2 + 0.1–0.3 ml IT oxytocin for 4 days, and Group 4 received same dose of cisplatin as Groups 2 and 3 + IP oxytocin with dose of 1 mg/kg. DPOAE was performed prior to procedure and at the end of the experiment on day 5.

Results

Group 2 showed severe ototoxic effect of cisplatin according to DPOAE result (p < 0.05). When compared with Group 2, DPOAE amplitude reductions were smaller in Group 3 (3.2, 3.8, 4.5, 6.3 and 7.6 kHz) (p < 0.05) and Group 4 which is statistically significant in 5.4, 6.3 and 7.6 kHz (p < 0.05). When Group 3 and Group 4 were compared, reductions were smaller in 2.7 and 3.2 kHz in Group 3 (p < 0.05).

Conclusion

In this study, we showed the protective effect of IT and IP oxytocin on cisplatin ototoxicity. We suggest oxytocin in cisplatin ototoxicity, especially via IT route even with high-dose cisplatin.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

References

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

    Article  CAS  PubMed  Google Scholar 

  2. Fausti SA, Henry JA, Schaffer HI, Olson DJ, Frey RH, Bagby GC Jr (1993) High-frequency monitoring for early detection of cisplatin ototoxicity. Arch Otolaryngol Head Neck Surg 119:661–666

    Article  CAS  PubMed  Google Scholar 

  3. 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  PubMed Central  Google Scholar 

  4. Rybak LP (2007) Mechanisms of cisplatin ototoxicity and progress in otoprotection. Curr Opin Otolaryngol Head Neck Surg 15:364–369

    Article  PubMed  Google Scholar 

  5. Kalkanis JG, Whitworth C, Rybak LP (2004) Vitamin E reduces cisplatin ototoxicity. Laryngoscope 114:538–542

    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. Xie J, Talaska AE, Schacht J (2011) New developments in aminoglycoside therapy and ototoxicity. Hear Res 281:28–37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Tugtepe H, Sener G, Biyikli NK, Yuksel M, Cetinel S, Gedik N, Yegen BC (2007) The protective effect of oxytocin on renal ischemia/reperfusion injury in rats. Regul Pept 140:101–108

    Article  CAS  PubMed  Google Scholar 

  9. Dusunceli F, Iseri SO, Ercan F, Gedik N, Yegen C, Yegen BC (2008) Oxytocin alleviates hepatic ischemia–reperfusion injury in rats. Peptides 29:1216–1222

    Article  CAS  PubMed  Google Scholar 

  10. Elberry AA, Refaie SM, Kamel M, Ali T, Darwish H, Ashourg O (2013) Oxytocin ameliorates cisplatin-induced nephrotoxicity in Wistar rats. Ann Saudi Med 33:57–62

    PubMed  Google Scholar 

  11. Ramesh G, Reeves WB (2005) p38 MAP kinase inhibition ameliorates cisplatin nephrotoxicity in mice. Am J Physiol Renal Physiol 289:166–174

    Article  Google Scholar 

  12. Tsuruya K, Tokumoto M, Ninomiya T, Hirakawa M, Masutani K, Taniguchi M et al (2003) Antioxidant ameliorates cisplatin-induced renal tubular cell death through inhibition of death receptor-mediated pathways. Am J Physiol Renal Physiol 285:208–218

    Article  Google Scholar 

  13. Horner KC, Lenoir M, Bock GR (1985) Distortion product otoacoustic emissions in hearing-impaired mutant mice. J Acoust Soc Am 78:1603–1611

    Article  CAS  PubMed  Google Scholar 

  14. Wimmer C, Mees K, Stumpf P, Welsch U, Reichel O, Suckfull M (2004) Round window application of d-methionine, sodium thiosulfate, brain-derived neurotrophic factor and fibroblast growth factor-2 in cisplatin-induced ototoxicity. Otol Neurotol 25:33–40

    Article  PubMed  Google Scholar 

  15. Ahn H, Lee E, Kim K, Lee C (1994) Effect of glutathione and its related enzymes on chemosensitivity of renal cell carcinoma and bladder carcinoma cell lines. J Urol 151:263–267

    CAS  PubMed  Google Scholar 

  16. Kimura C, Zhao QL, Kondo T, Amatsu M, Fujiwara Y (1998) Mechanism of UV-induced apoptosis in human leukemia cells: roles of Ca2+/Mg(2+)-dependent endonuclease, caspase-3, and stress-activated protein kinases. Exp Cell Res 239:411–422

    Article  CAS  PubMed  Google Scholar 

  17. Rashed LA, Hashem RM, Soliman HM (2011) Oxytocin inhibits NADPH oxidase and P38 MAPK in cisplatin-induced nephrotoxicity. Biomed Pharmacother 65:474–480

    Article  CAS  PubMed  Google Scholar 

  18. Kitano H, Takeda T, Suzuki M, Kitanishi T, Yazawa Y, Kitajima K, Kimura H (1997) Vasopressin and oxytocin receptor mRNAs are expressed in the rat inner ear. Neuroreport 8:2289–2291

    Article  CAS  PubMed  Google Scholar 

  19. Gonser M (1995) Labor induction and augmentation with oxytocin: pharmacokinetic considerations. Arch Gynecol Obstet 256(2):63–66

    Article  CAS  PubMed  Google Scholar 

  20. Juhn SK, Hamaguchi Y, Goycoolea M (1989) Review of round window membrane permeability. Acta Otolaryngol 457:43–48

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sedat Aydin.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bekmez Bilmez, Z.E., Aydin, S., Şanli, A. et al. Oxytocin as a protective agent in cisplatin-induced ototoxicity. Cancer Chemother Pharmacol 77, 875–879 (2016). https://doi.org/10.1007/s00280-016-2978-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-016-2978-x

Keywords

Navigation