Otoprotective effects of farnesene against oxidative damage induced by paclitaxel
Öz
Purpose: This study explores the biochemical and functional effects of farnesene, which has potent free radical scavenging and antioxidant properties, on paclitaxel-induced ototoxicity.
Materials and Methods: Eighteen male Wistar albino rats were allocated into three groups of six rats at random. No paclitaxel or farnesene was given to the control group throughout the research. Paclitaxel was given four times intraperitoneally at a dose of 5 mg/kg (1st, 7th, 14th & 21st days) in the paclitaxel group. In the Farnesene + Paclitaxel group, 5 mg/kg paclitaxel was given first, followed by 4 times 50 mg/kg farnesene intraperitoneally 30 minutes later (1st, 7th, 14th & 21st days). Otoacoustic emission measurement was taken on days 0 and 21 in all rats. After that, the animals were sacrificed, and their cochleas were extracted for biochemical testing.
Results: Paclitaxel caused oxidative stress in the cochlea, which considerably elevated malondialdehyde levels and lowered glutathione levels in cochlear tissues. Furthermore, the paclitaxel group’s distortion product otoacoustic emission values were significantly lower than the other groups. Improvements in the damage produced by paclitaxel in various biochemical and functional parameters were observed in the Farnesene+Paclitaxel group.
Conclusion: The study findings imply that farnesene, a natural antioxidant, reduced paclitaxel-induced hearing loss in rats, and a combination of farnesene and paclitaxel therapy may have protected from paclitaxel-induced ototoxicity for future clinical use.
Anahtar Kelimeler
Antioxidants, Farnesene, Otoacoustic emission, Ototoxicity; Paclitaxel, Ototoxicity
Kaynakça
- Lanvers‐Kaminsky C, Zehnhoff‐Dinnesen AGa, Parfitt R, Ciarimboli G. Drug‐induced ototoxicity: mechanisms, pharmacogenetics, and protective strategies. Clinical pharmacology & therapeutics. 2017; 101:491-500.
- Paken J, Govender CD, Pillay M, Sewram V. Cisplatin-associated ototoxicity: a review for the health professional. Journal of Toxicology. 2016; 2016:1-13.
- Knight KRG, Kraemer DF,Neuwelt EA. Ototoxicity in children receiving platinum chemotherapy: underestimating a commonly occurring toxicity that may influence academic and social development. Journal of Clinical Oncology. 2005; 23:8588-96. Bicaku E, Xiong Y, Marchion DC, Chon HS, Stickles XB, Chen N et al. In vitro analysis of ovarian cancer response to cisplatin, carboplatin, and paclitaxel identifies common pathways that are also associated with overall patient survival. British journal of cancer. 2012; 106:1967-75.
- Bachegowda LS, Makower DF,Sparano JA. Taxanes: impact on breast cancer therapy. Anti-cancer drugs. 2014; 25:512-21.
- Sakai H, Yoneda S, Tamura T, Nishiwaki Y, Yokoyama A, Watanabe K, Saijo N. A phase II study of paclitaxel plus cisplatin for advanced non-small-cell lung cancer in Japanese patients. Cancer chemotherapy and pharmacology. 2001; 48:499-503.
- Misiukiewicz K, Gupta V, Bakst R,Posner M. Taxanes in cancer of the head and neck. Anti-cancer drugs. 2014; 25:561-70.
- Weaver BA. How Taxol/paclitaxel kills cancer cells. Molecular biology of the cell. 2014; 25:2677-81.
- Park SB, Lin CSY, Krishnan AV, Friedlander ML, Lewis CR, Kiernan MC. Early, progressive, and sustained dysfunction of sensory axons underlies paclitaxel‐induced neuropathy. Muscle & nerve. 2011; 43:367-74.
- Pace A, Nisticò C, Cuppone F, Bria E, Galiè E, Graziano G et al. Peripheral neurotoxicity of weekly paclitaxel chemotherapy: a schedule or a dose issue? Clinical breast cancer. 2007; 7:550-54.
- Dong Y, Ding D, Jiang H, Shi J-r, Salvi R, Roth JA. Ototoxicity of paclitaxel in rat cochlear organotypic cultures. Toxicology and applied pharmacology. 2014; 280:526-33.
