Yıl: 2021 Cilt: 11 Sayı: 2 Sayfa Aralığı: 318 - 323 Metin Dili: İngilizce DOI: 10.5505/kjms.2021.59375 İndeks Tarihi: 01-02-2022

The Protective Effect of Taxifolin Against Amikacin-induced Ototoxicity in Rats: a Biochemical and Histopathological Evaluation

Öz:
Aim: Amikacin is a semi-synthetic aminoglycoside derivative antibacterial drug. Amikacin’s cochleotoxic effects causing permanent hearing loss have been reported. Over-production of reactive oxygen species (ROS) are responsible for the ototoxicity of amikacin. The study investigates the protective effect of Taxifolin (3.5.7.3.4-pentahydroxy flavanone), an antioxidant flavonoid, against amikacin-induced ototoxicity. The objective is to biochemically and histopathologically investigate the protective effect of taxifolin against amikacin-induced ototoxicity in male albino Wistar rats. Material and Method: TAK group animals were administered taxifolin 50 mg/kg (n-6) by oral gavage. AMK (n-6) and HG (n-6) groups were administered distilled water as solvent using the same method. One hour after taxifolin and distilled water administration, TAK and AMK groups were given 200 mg/kg amikacin by intramuscular route. This procedure was performed once a day for 14 days. Cochlear tissues extracted from the animals killed after this period with high doses of ketamine (120 mg/kg) were investigated biochemically and histopathologically. Results: Histopathological damage such as edema and deconstruction was observed in cochlear tissues of the AMK group where malondialdehyde (MDA) and total oxidant status (TOS) were high and total glutathione (tGSH) and total antioxidant status (TAS) were low. However, no histopathological finding except for mild edema was observed in the TAK group where MDA, TOS, tGSH, and TAS levels were close to those of the HG group. Conclusion: Taxifolin may be beneficial in terms of preventing amikacin-induced cochlear damage.
Anahtar Kelime:

Taxifolinin Sıçanlarda Amikasin ile İndüklenen Ototoksisiteye Karşı Koruyucu Etkisi: Biyokimyasal ve Histopatolojik Değerlendirme

Öz:
Amaç: Amikasin, yarı sentetik aminoglikozid türevi antibakteriyel bir ilaçtır. Amikasinin kalıcı işitme kaybına yol açan kokleotoksik etkileri rapor edilmiştir. Amikasin ototoksisitesinden, reaktif oksijen türlerinin (ROS) aşırı üretimi sorumlu tutulmaktadır. Çalışmamızda amikasin ile indüklenen ototoksisiteye karşı koruyucu etkisini araştıracağımız Taxifolin (3.5.7,3,4-pentahydroxy flavanone) antioksidan bir flavonoiddir. Taxifolinin albino Wistar türü erkek sıçanlarda amikasin ile indüklenen ototoksisiteye karşı koruyucu etkisini biyokimyasal ve histopatolojik olarak araştırmak amaçlanmaktadır. Materyal ve Metot: Hayvanların TAK grubuna taxifolin 50 mg/kg (n-6) oral yoldan gavajla verildi. AMK (n-6) ve HG (n-6) gruplarına ise çözücü olarak distile su aynı hacimde aynı yöntemle uygulandı. Taxifolin ve distile su verildikten bir saat sonra TAK ve AMK gruplarına amikasin 200 mg/kg intramusküler yoldan enjekte edildi. Bu prosedür günde bir defa 14 gün boyunca uygulandı. Bu süre sonunda yüksek doz ketamile (120 mg/kg) öldürülen hayvanlardan çıkarılan koklea dokuları biyokimyasal ve histopatolojik olarak incelendi. Bulgular: Malondialdehid (MDA) ve total oksidan statusun (TOS) yüksek, total glutatyon (tGSH) ve total antioksidan statüsun (TAS) düşük bulunduğu AMK grubunun koklea dokusunda ödem ve destrüksiyon gibi histopatolojik hasar görülmüştür. Ancak, MDA, TOS, tGSH ve TAS düzeyleri HG grubuna yakın olan TAK grubunda hafif ödem dışında herhangi bir histopatolojik bulgulara rastlanmadı. Sonuç: Taksifolin, amikasinle ilişkili koklea hasarının önlenmesinde yararlı olabileceğini işaret etmektedir.
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • 1. Selimoglu E. Aminoglycoside-induced ototoxicity. Curr Pharm Des 2007;13(1):119–26.
  • 2. Hutchin T, Cortopassi G. Proposed molecular and cellular mechanism for aminoglycoside ototoxicity. Antimicrob Agents Chemother 1994;38(11):2517–20.
  • 3. Begg EJ, Barclay ML. Aminoglycosides:50 years on. Br J Clin Pharmacol 1995 6;39(6):597–603.
  • 4. Aksoy F, Dogan R, Ozturan O, Tugrul S, Veyseller B, Ozer OF, et al. An evaluation of the protective effects of thymoquinone on amikacin-ınduced ototoxicity in rats. Clin Exp Otorhinolaryngol 2015;8(4):312–19.
  • 5. Murillo-Cuesta S, Contreras J, Cediel R, Varela-Nieto I. Comparison of different aminoglycoside antibiotic treatments to refine ototoxicity studies in adult mice. Lab Anim 2014;44(2):124–31.
  • 6. World Health OrganizationReport of an Informal Consultation on Strategies for Prevention of Hearing Impairment from Ototoxic Drugs, vol 95, WHO/PDH(1994), p.2.
  • 7. Huth ME, Ricci AJ, Cheng AG. Mechanisms of aminoglycoside ototoxicity and targets of hair cell protection. Int J Otolaryngol 2011;2011:937861.
  • 8. Rizzi MD, Hirose K. Aminoglycoside ototoxicity. Curr Opin Otolaryngol Head Neck Surg 2007;15(5):352–57.
  • 9. Aksoy F, Dogan R, Ozturan O, Eren SB, Veyseller B, Pektas A, et al. Protective effect of trimetazidine on amikacininduced ototoxicity in rats. Int J Pediatr Otorhinolaryngol 2014;78(4):663–69.
  • 10. Rice-Evans CA, Miller NJ, Paganga G. Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med 1996;20(7):933–56.
  • 11. Cotelle N. Role of flavonoids in oxidative stress. Curr Top Med Chem 2001;1(6):569–90.
  • 12. Ahiskali I, Pinar CL, Kiki M, Cankaya M, Kunak CS, Altuner D. Effect of taxifolin on methanol-induced oxidative and inflammatory optic nerve damage in rats. Cutan Ocul Toxicol 2019;12:1–6.
  • 13. Eken H, Cimen O, Cimen FK, Kurnaz E, Yildirim M, Tasova V, et al. Effect of taxifolin on oxidative gastric injury induced by celiac artery ligation in rats. Acta Cir Bras 2019;34(4): e201900404.
  • 14. Unver E, Tosun M, Olmez H, Kuzucu M, Cimen FK, Suleyman Z. The effect of taxifolin on cisplatin-ınduced pulmonary damage in rats: a biochemical and histopathological evaluation. Mediators Inflamm 2019;12:3740867.
  • 15. Topal F, Nar M, Gocer H, Kalin P, Kocyigit UM, Gülçin İ, et al. Antioxidant activity of taxifolin: an activity-structure relationship. J Enzyme Inhib Med Chem 2016;31(4):674–83.
  • 16. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95(2):351–8.
  • 17. Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem 1968;25(1):192–205.
  • 18. Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem 2004;37:112–9.
  • 19. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005;38:1103–11.
  • 20. Klemens JJ, Meech RP, Hughes LF, Somani S, Campbell K. Antioxidant enzyme levels ınversely covary with hearing loss after amikacin treatment. J Am Acad Audiol 2003;14(3):134–43.
  • 21. Kisaoglu A, Borekci B, Yapca OE, Bilen H, Suleyman H. Tissue damage and oxidant/antioxidant balance. Eurasian J Med 2013;45(1):47–9.
  • 22. Del Rio D, Stewart AJ, Pellegrini N. A review of recent stud¬ies on malondialdehyde as toxic molecule and biological marker of oxidative stress. Nutr Metab Cardiovasc Dis 2005;15:316–28.
  • 23. Draper H, Hadley M. Malondialdehyde determination as in¬dex of lipit peroxidation. Methods Enzymol 1990;186:421– 31.
  • 24. Slater TF. Free-radical mechanisms in tissue injury. Biochem J 1984;222:1–15.
  • 25. Murray RK, Granner DK, Mayes PA, VM. R. Harper’s Biochemistry 25. Baskı. USA, McGraw-Hill Press, 2000.
  • 26. Lenoir M, Daudet N, Humbert G, Renard N, Gallego M, Pujol R, et al. Morphological and Molecular Changes in the Inner Hair Cell Region of the Rat Cochlea After Amikacin Treatment. J Neurocytol 1999;28(10–11):925–37.
  • 27. Cazals Y, Aran JM, Erre JP, Guilhaume A. Acoustic responses after total destruction of the cochlear receptor: brainstem and auditory cortex. Science 1980;210(4465):83–6.
  • 28. Tang Z, Yang C, Zuo B, Zhang Y, Wu G, Wang Y, et al. Taxifolin protects rat against myocardial ischemia/reperfusion ınjury by modulating the mitochondrial apoptosis pathway. Peer J 2019;31(7): e6383.
  • 29. Ye Y, Wang X, Cai Q, Zhuang J, Tan X, He W, et al. Protective Effect of Taxifolin on H2O2-induced H9C2 Cell Pyroptosis. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2017;42(12):1367– 74.
  • 30. Cai C, Liu C, Zhao L, Liu H, Li W, Guan H, et al. Effects of taxifolin on osteoclastogenesis in vitro and in vivo. Front Pharmacol 2018;12(9):1286.
APA Erhan E, salcan i, Dilber M, Gürsul C, karahan s, ÇOBAN T, KESKIN ÇIMEN F, Suleyman H (2021). The Protective Effect of Taxifolin Against Amikacin-induced Ototoxicity in Rats: a Biochemical and Histopathological Evaluation. , 318 - 323. 10.5505/kjms.2021.59375
Chicago Erhan Ertugrul,salcan ismail,Dilber Muhammet,Gürsul Cebrail,karahan sevil,ÇOBAN T. Abdulkadir,KESKIN ÇIMEN FERDA,Suleyman Halis The Protective Effect of Taxifolin Against Amikacin-induced Ototoxicity in Rats: a Biochemical and Histopathological Evaluation. (2021): 318 - 323. 10.5505/kjms.2021.59375
MLA Erhan Ertugrul,salcan ismail,Dilber Muhammet,Gürsul Cebrail,karahan sevil,ÇOBAN T. Abdulkadir,KESKIN ÇIMEN FERDA,Suleyman Halis The Protective Effect of Taxifolin Against Amikacin-induced Ototoxicity in Rats: a Biochemical and Histopathological Evaluation. , 2021, ss.318 - 323. 10.5505/kjms.2021.59375
AMA Erhan E,salcan i,Dilber M,Gürsul C,karahan s,ÇOBAN T,KESKIN ÇIMEN F,Suleyman H The Protective Effect of Taxifolin Against Amikacin-induced Ototoxicity in Rats: a Biochemical and Histopathological Evaluation. . 2021; 318 - 323. 10.5505/kjms.2021.59375
Vancouver Erhan E,salcan i,Dilber M,Gürsul C,karahan s,ÇOBAN T,KESKIN ÇIMEN F,Suleyman H The Protective Effect of Taxifolin Against Amikacin-induced Ototoxicity in Rats: a Biochemical and Histopathological Evaluation. . 2021; 318 - 323. 10.5505/kjms.2021.59375
IEEE Erhan E,salcan i,Dilber M,Gürsul C,karahan s,ÇOBAN T,KESKIN ÇIMEN F,Suleyman H "The Protective Effect of Taxifolin Against Amikacin-induced Ototoxicity in Rats: a Biochemical and Histopathological Evaluation." , ss.318 - 323, 2021. 10.5505/kjms.2021.59375
ISNAD Erhan, Ertugrul vd. "The Protective Effect of Taxifolin Against Amikacin-induced Ototoxicity in Rats: a Biochemical and Histopathological Evaluation". (2021), 318-323. https://doi.org/10.5505/kjms.2021.59375
APA Erhan E, salcan i, Dilber M, Gürsul C, karahan s, ÇOBAN T, KESKIN ÇIMEN F, Suleyman H (2021). The Protective Effect of Taxifolin Against Amikacin-induced Ototoxicity in Rats: a Biochemical and Histopathological Evaluation. Kafkas Tıp Bilimleri Dergisi, 11(2), 318 - 323. 10.5505/kjms.2021.59375
Chicago Erhan Ertugrul,salcan ismail,Dilber Muhammet,Gürsul Cebrail,karahan sevil,ÇOBAN T. Abdulkadir,KESKIN ÇIMEN FERDA,Suleyman Halis The Protective Effect of Taxifolin Against Amikacin-induced Ototoxicity in Rats: a Biochemical and Histopathological Evaluation. Kafkas Tıp Bilimleri Dergisi 11, no.2 (2021): 318 - 323. 10.5505/kjms.2021.59375
MLA Erhan Ertugrul,salcan ismail,Dilber Muhammet,Gürsul Cebrail,karahan sevil,ÇOBAN T. Abdulkadir,KESKIN ÇIMEN FERDA,Suleyman Halis The Protective Effect of Taxifolin Against Amikacin-induced Ototoxicity in Rats: a Biochemical and Histopathological Evaluation. Kafkas Tıp Bilimleri Dergisi, vol.11, no.2, 2021, ss.318 - 323. 10.5505/kjms.2021.59375
AMA Erhan E,salcan i,Dilber M,Gürsul C,karahan s,ÇOBAN T,KESKIN ÇIMEN F,Suleyman H The Protective Effect of Taxifolin Against Amikacin-induced Ototoxicity in Rats: a Biochemical and Histopathological Evaluation. Kafkas Tıp Bilimleri Dergisi. 2021; 11(2): 318 - 323. 10.5505/kjms.2021.59375
Vancouver Erhan E,salcan i,Dilber M,Gürsul C,karahan s,ÇOBAN T,KESKIN ÇIMEN F,Suleyman H The Protective Effect of Taxifolin Against Amikacin-induced Ototoxicity in Rats: a Biochemical and Histopathological Evaluation. Kafkas Tıp Bilimleri Dergisi. 2021; 11(2): 318 - 323. 10.5505/kjms.2021.59375
IEEE Erhan E,salcan i,Dilber M,Gürsul C,karahan s,ÇOBAN T,KESKIN ÇIMEN F,Suleyman H "The Protective Effect of Taxifolin Against Amikacin-induced Ototoxicity in Rats: a Biochemical and Histopathological Evaluation." Kafkas Tıp Bilimleri Dergisi, 11, ss.318 - 323, 2021. 10.5505/kjms.2021.59375
ISNAD Erhan, Ertugrul vd. "The Protective Effect of Taxifolin Against Amikacin-induced Ototoxicity in Rats: a Biochemical and Histopathological Evaluation". Kafkas Tıp Bilimleri Dergisi 11/2 (2021), 318-323. https://doi.org/10.5505/kjms.2021.59375