Differential Amelioration of Aminoglycoside-Induced Oxidative Stress by Virgin Coconut Oil in the Vestibulocochlear Tissue and Serum of Wistar Rats
DOI:
https://doi.org/10.64348/zije.2026366Abstract
Aminoglycoside (AG)-induced ototoxicity is primarily driven by the generation of reactive oxygen species (ROS) within the inner ear, leading to irreversible hair cell damage and death. Virgin coconut oil (VCO) is a natural product with potent antioxidant properties, but its specific effect on ROS levels within the vestibulocochlear tissue was unexplored. This study investigated the differential effects of VCO on concentrations of total ROS and inflammatory cytokine in the vestibulocochlear tissue and serum of rats treated with gentamicin (GTM). Thirty male Wistar rats were divided into six groups (n=5): normal control, GTM-only (80 mg/kg i.p.), GTM + Vitamin E (20 IU/kg, p.o.), and three GTM + VCO groups (1, 5, and 10 ml/kg, p.o.). Treatments were for 30 days, following which animals were sacrificed and serum and vestibulocochlear tissue homogenates were collected and assessed for total ROS, interleukin-1β (IL-1β), and tumor necrosis factor-alpha (TNF-α) using enzyme-linked immunosorbent assay (ELISA) kits. GTM treatment significantly elevated total ROS concentrations in both the vestibulocochlear tissue (146.02 ± 15.95 µg/mL) and serum (107.50 ± 1.29 µg/mL) compared to controls (tissue: 125.19 ± 2.68 µg/mL; serum: 87.49 ± 4.38 µg/mL; p < 0.05). Co-administration with VCO at all doses (1, 5, and 10 ml/kg) significantly reduced tissue ROS levels below control values (p < 0.05), with the 5 ml/kg dose being the most effective (83.59 ± 2.92 µg/mL). VCO was found to exert dose-dependent antioxidant effect on total ROS and TNF-α. These findings provide a biochemical basis for VCO's otoprotective effects al as a therapeutic adjuvant during AG therapy.
References
Alghamdi, B. S. A. (2018). Possible prophylactic anti-excitotoxic and anti-oxidant effects of virgin coconut oil on aluminium chloride-induced Alzheimer’s in rat models. Journal of Integrative Neuroscience, 17(3–4), 593–607. DOI: https://doi.org/10.3233/JIN-180089
Arunima, S., & Rajamohan, T. (2014). Influence of virgin coconut oil-enriched diet on the transcriptional regulation of fatty acid synthesis and oxidation in rats – a comparative study. British Journal of Nutrition, 111(10), 1782–1790. DOI: https://doi.org/10.1017/S000711451400004X
Blunston, M. A., Yonovitz, A., Woodahl, E. L., & Smolensky, M. H. (2015). Gentamicin-induced ototoxicity and nephrotoxicity vary with circadian time of treatment and entail separate mechanisms. Chronobiology International, 32(9), 1223–1232. DOI: https://doi.org/10.3109/07420528.2015.1082483
Bowry, V. W., & Stocker, R. (1993). Tocopherol-mediated peroxidation. The prooxidant effect of vitamin E on the radical-initiated oxidation of human low-density lipoprotein. Journal of the American Chemical Society, 115(14), 6029-6044. DOI: https://doi.org/10.1021/ja00067a019
Campbell, K. C., Martin, S. M., Meech, R. P., Hargrove, T. L., Verhulst, S. J., & Fox, D. J. (2016). D-methionine (D-met) significantly reduces kanamycin-induced ototoxicity in pigmented guinea pigs. International Journal of Audiology, 55(5), 273–278. DOI: https://doi.org/10.3109/14992027.2016.1143980
Cao, L., Zhi, D., Han, J., Kumar Sah, S., & Xie, Y. (2019). Combinational effect of curcumin and metformin against gentamicin-induced nephrotoxicity: Involvement of antioxidative, anti-inflammatory and antiapoptotic pathway. Journal of Food Biochemistry, 43(7). DOI: https://doi.org/10.1111/jfbc.12836
Clerici, W. J., DiMartino, D. L., & Prasad, M. R. (2005). Direct effects of reactive oxygen species on cochlear outer hair cell shape in vitro. Hearing Research, 84(1-2), 30–40. DOI: https://doi.org/10.1016/0378-5955(95)00010-2
Eshraghi, A. A., Wang, J., Adil, E., He, J., Zine, A., Bublik, M., ... & Van De Water, T. R. (2007). Blocking c-Jun-N-terminal kinase signaling can prevent hearing loss induced by both electrode insertion trauma and neomycin ototoxicity. Hearing Research, 226(1-2), 168-177. DOI: https://doi.org/10.1016/j.heares.2006.09.008
Famurewa, A. C., Maduagwuna, E. K., Folawiyo, A. M., Besong, E. E., Eteudo, A. N., Famurewa, O. A., & Ejezie, F. E. (2020). Antioxidant, anti‐inflammatory, and antiapoptotic effects of virgin coconut oil against antibiotic drug gentamicin‐induced nephrotoxicity via the suppression of oxidative stress and modulation of iNOS/NF‐ĸB/caspase‐3 signaling pathway in Wistar rats. Journal of Food Biochemistry, 44(1), e13100. DOI: https://doi.org/10.1111/jfbc.13100
Fetoni, A. R., Eramo, S. L. M., Rolesi, R., Troiani, D., & Paludetti, G. (2012). Antioxidant treatment with coenzyme Q-ter in prevention of gentamycin ototoxicity in an animal model. Acta Otorhinolaryngologica Italica, 32(2), 103-110.
Frymark, T., Leech, H., Mullen, R., Schooling, T., Venediktov, R., & Wang, B. (2010). Evidence-Based Systematic Review: Drug-Induced Hearing Loss-Gentamicin. ASHA’s National Center for Evidence-Based Practice in Communication Disorders.
Fu, X., Wan, P., Li, P., Wang, J., Guo, S., Zhang, Y., ... & Chai, R. (2021). Mechanism and Prevention of Ototoxicity Induced by Aminoglycosides. Frontiers in Cellular Neuroscience, 15, 692762. DOI: https://doi.org/10.3389/fncel.2021.692762
Heysell, S. K., Ahmed, S., Rahman, M. T., Akhanda, M. W., Gleason, A. T., Ebers, A., ... & Banu, S. (2018). Hearing loss with kanamycin treatment for multidrug-resistant tuberculosis in Bangladesh. European Respiratory Journal, 51(3), 1701778. DOI: https://doi.org/10.1183/13993003.01778-2017
Hirose, K., & Liberman, M. C. (2003). Lateral wall histopathology and endocochlear potential in the noise-damaged mouse cochlea. Journal of the Association for Research in Otolaryngology, 4(3), 339–352. DOI: https://doi.org/10.1007/s10162-002-3036-4
Huth, M. E., Ricci, A. J., & Cheng, A. G. (2011). Mechanisms of Aminoglycoside Ototoxicity and Targets of Hair Cell Protection. International Journal of Otolaryngology, 2011, 937861. DOI: https://doi.org/10.1155/2011/937861
Intahphuak, S., Khonsung, P., & Panthong, A. (2010). Anti-inflammatory, analgesic, and antipyretic activities of virgin coconut oil. Pharmaceutical Biology, 48(2), 151–157. DOI: https://doi.org/10.3109/13880200903062614
Kharkheli, E. S., Kevanishvili, Z., Maglakelidze, T., Davitashvili, O. Z., & Schacht, J. (2007). Does vitamin E prevent gentamicin-induced ototoxicity? Georgian Medical News, 146, 14-17.
Marcotti, W., van Netten, S. M., & Kros, C. J. (2005). The aminoglycoside antibiotic dihydrostreptomycin rapidly enters mouse outer hair cells through the mechano-electrical transducer channels. The Journal of Physiology, 567(2), 505-521. DOI: https://doi.org/10.1113/jphysiol.2005.085951
Marina, A. M., Che Man, Y. B., & Amin, I. (2009). Virgin coconut oil: emerging functional food oil. Trends in Food Science & Technology, 20(10), 481-487. DOI: https://doi.org/10.1016/j.tifs.2009.06.003
Modongo, C., Pasipanodya, J. G., Zetola, N. M., Williams, S. M., Sirugo, G., & Gumbo, T. (2015). Amikacin Concentrations Predictive of Ototoxicity in Multidrug-Resistant Tuberculosis Patients. Antimicrobial Agents and Chemotherapy, 59(10), 6337–6343. DOI: https://doi.org/10.1128/AAC.01050-15
Molina, A., Moyano, R., Serrano-Rodríguez, J., Ayala, N., Lora, A. J., & Serrano, J. M. (2015). Analysis of anaesthesia with ketamine combined with different sedatives in rats. Veterinární Medicína, 60(7), 368-375. DOI: https://doi.org/10.17221/8384-VETMED
Neal, C. A., Nelson-Brantley, J. G., Detamore, M. S., Staecker, H., & Mellott, A. J. (2018). A Protocol for Decellularizing Mouse Cochleae for Inner Ear Tissue Engineering. Journal of Visualized Experiments, (131), e56523. DOI: https://doi.org/10.3791/56523-v
Neuzil, J., Thomas, S. R., & Stocker, R. (1997). Requirement for, and promotion of, protein oxidation by, and inhibition of protein oxidation by, alpha-tocopherol. Free Radical Biology and Medicine, 23(1), 57-71. DOI: https://doi.org/10.1016/S0891-5849(96)00224-9
Nevin, K. G., & Rajamohan, T. (2004). Beneficial effects of virgin coconut oil on lipid parameters and in vitro LDL oxidation. Clinical Biochemistry, 37(9), 830–835. DOI: https://doi.org/10.1016/j.clinbiochem.2004.04.010
Nevin, K. G., & Rajamohan, T. (2006). Virgin coconut oil supplemented diet increases the antioxidant status in rats. Food Chemistry, 99(2), 260–266. DOI: https://doi.org/10.1016/j.foodchem.2005.06.056
Rahim, N. S., Lim, S. M., Mani, V., Abdul Majeed, A. B., & Ramasamy, K. (2017). Enhanced memory in Wistar rats by virgin coconut oil is associated with increased antioxidative, cholinergic activities and reduced oxidative stress. Pharmaceutical Biology, 55(1), 825–832. DOI: https://doi.org/10.1080/13880209.2017.1280688
Rizk, H. G., Lee, J. A., Liu, Y. F., Endriukaitis, L., Isaac, J. L., & Bullington, W. M. (2020). Drug-Induced Ototoxicity: A Comprehensive Review and Reference Guide. Pharmacotherapy, 40(12), 1265–1275. DOI: https://doi.org/10.1002/phar.2478
Schacht, J., Talaska, A. E., & Rybak, L. P. (2012). Cisplatin and Aminoglycoside Antibiotics: Hearing Loss and Its Prevention. The Anatomical Record, 295(11), 1837–1850. DOI: https://doi.org/10.1002/ar.22578
Selimoglu, E. (2007). Aminoglycoside-Induced Ototoxicity. Current Pharmaceutical Design, 13(1), 119–126. DOI: https://doi.org/10.2174/138161207779313731
Sha, S. H., & Schacht, J. (2000). Antioxidants attenuate gentamicin-induced free radical formation in vitro and ototoxicity in vivo: D-methionine is a potential protectant. Hearing Research, 142(1-2), 34–40. DOI: https://doi.org/10.1016/S0378-5955(00)00003-4
Singh, U., Devaraj, S., & Jialal, I. (2005). Vitamin E, Oxidative Stress, And Inflammation. Annual Review of Nutrition, 25(1), 151–174. doi:10.1146/annurev.nutr.24.0120 DOI: https://doi.org/10.1146/annurev.nutr.24.012003.132446
Wei, X., Zhao, L., Liu, J., Dodel, R. C., Farlow, M. R., & Du, Y. (2005). Minocycline prevents gentamicin-induced ototoxicity by inhibiting p38 MAP kinase phosphorylation and caspase 3 activation. Neuroscience, 131(2), 513–521. DOI: https://doi.org/10.1016/j.neuroscience.2004.11.014
Yusuf, A., Alhassan, A. W., Saleh, M. I. A., Adamu, B. Y., Olaide, L., Jamila, Z., & Aisha, Y. (2016). Anticonvulsant effects of Virgin coconut-oil, sodium valproate and phenobarbital in Wistar rats. Archives of Basic & Applied Medicine, 4, 121-124.
Zekrumah, M., Begua, P., Razak, A., Wahab, J., Moffo, N., Ivane, A., & Zhang, D. (2023). Role of dietary polyphenols in non-communicable chronic disease prevention, and interactions in food system: an overview. Nutrition, 112, 112034. DOI: https://doi.org/10.1016/j.nut.2023.112034
