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Effect Of Zinc Administration in Preventing Ethambutol-Induced Optic Neuropathy in Wistar Rats Model

1Department of Ophthalmology, Universitas Diponegoro, Indonesia

2Department of Anatomical Pathology, Universitas Diponegoro, Indonesia

Received: 12 Apr 2023; Revised: 27 Jul 2023; Accepted: 7 Aug 2023; Available online: 31 Aug 2023; Published: 31 Aug 2023.
Open Access Copyright (c) 2023 Journal of Biomedicine and Translational Research
Creative Commons License This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

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Abstract

Background: Ethambutol-induced optic neuropathy (E-TON) is one of the most common optic neuropathies, especially in developing countries with an increasing rate of Tuberculosis (TB). Various outcomes of visual impairment that may lead to permanent visual loss makes it imperative to prescribe supplementation to prevent E-TON. Zinc supplementation is suggested as one of many to prevent E-TON given that ethambutol is a Zn chelator.

Purpose: To analyze the apoptosis rate of retinal ganglion cell (RGC) in Wistar rats given ethambutol and Zinc supplementation.

Methods: Experimental analysis research. True – experimental design and post-test only using Wistar rats. Subjects were divided into 2 groups, treatment grup was given Ethambutol and Zn and control group was given ethambutol without Zn for 30 days. Assessment of apoptosis rate was concluded by an anatomical pathologist with histopathological scoring using Hematoxylin Eosin staining. Differences between two grups were statistically analyzed using Mann Whitney U test, (Signifikan p <0,05).

Results: From Distribution of rate apoptosis in treatment group was found 28.6% without apoptosis, 71.4% score 1 and no score > 1. There was a significantly different in apoptosis retinal ganglion cell between two grups (p= 0.015).

Conclusion: The rate of retinal ganglion cell apoptosis was lower in rats treated ethambutol with Zn than without Zn.

 

 

 

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Keywords: E-TON; zinc; retinal ganglion cell

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  1. Depkes Republik Indonesia. InfoDatin tuberculosis. Kementerian Kesehatan RI. 2018;1–9
  2. Rapuono J.C. et all. Neuro-ophthalmology: optic neuropathy.American Academy of Ophtalmology. 2021;137–9
  3. Yang HK, Park MJ, Lee JH, Lee CT, Park JS, Hwang JM. Incidence of toxic optic neuropathy with low-dose ethambutol. The International Journal of Tuberculosis and Lung Disease. 2016 Feb 1;20(2):261–4. DOI: 10.5588/ijtld.15.0275
  4. Chung H, Yoon YH, Hwang JJ, Cho KS, Koh JY, Kim JG. Ethambutol-induced toxicity is mediated by zinc and lysosomal membrane permeabilization in cultured retinal cells. Toxicol Appl Pharmacol. 2009 Mar;235(2):163–70. DOI: 10.1016/j.taap.2008.11.006
  5. RYC Chan, AKH Kwok. Ocular toxicity of ethambutol. Hongkong Medical Journal. 2006;12(1):56–60. PMID: 16495590
  6. Indrayani I, Ariswanda I, Samatra D, Masputra A, Widyadharma I. CHARACTERISTICS OF ETHAMBUTOL OPTIC NEUROPATHY ON TUBERCULOSIS TREATMENT IN SANGLAH HOSPITAL DENPASAR. International Journal of Medical Reviews and Case Reports. 2019;(0):1
  7. Nur Azizah Juzmi, Batari Todja Umar, Rahasiah Taufik. NEUROPATI OPTIK TOKSIK SETELAH PEMBERIAN ETAMBUTOL PADA PENDERITA TUBERKULOSIS DI MAKASSAR. JST kesehatan. 2014;4(3):269–76
  8. Muhammad AM. Karakteristik pasien neuropati optik toksi etambutol di pusat mata nasional rumah sakit mata cicendo. Cicendo. 2019;1–8
  9. Heng JE, Vorwerk CK, Lessell E, Zurakowski D, Levin LA, Dreyer EB. Ethambutol is toxic to retinal ganglion cells via an excitotoxic pathway. Invest Ophthalmol Vis Sci. 1999 Jan;40(1):190–6. PMID: 9888443
  10. Yoon YH, Jung KH, Sadun AA, Shin HC, Koh JY. Ethambutol-Induced Vacuolar Changes and Neuronal Loss in Rat Retinal Cell Culture: Mediation by Endogenous Zinc. Toxicol Appl Pharmacol. 2000 Jan;162(2):107–14. DOI: 10.1006/taap.1999.8846
  11. Tsai RK, He MS, Chen ZY, Wu WC, Wu WS. PKCδ-dependent signaling mediates ethambutol-induced toxic effects on human retinal pigment cells. Mol Vis. 2011;17:1564–76
  12. Huang SP, Chien JY, Tsai RK. Ethambutol induces impaired autophagic flux and apoptosis in the retina. Dis Model Mech. 2015 Jan 1; DOI: 10.1242/dmm.019737
  13. Gong H, Amemiya T. Optic Nerve Changes in Zinc-deficient Rats. Exp Eye Res. 2001 Apr;72(4):363–9. DOI: 10.1006/exer.2000.0958
  14. Shindler KS, Zurakowski D, Dreyer EB. Caspase inhibitors block zinc-chelator induced death of retinal ganglion cells. Neuroreport. 2000 Jul;11(10):2299–302. DOI: 10.1097/00001756-200007140-00046
  15. Chen TA, Yang F, Cole GM, Chan SO. Inhibition of caspase-3-like activity reduces glutamate induced cell death in adult rat retina11Published on the World Wide Web on 9 May 2001. Brain Res. 2001 Jun;904(1):177–88. DOI: 10.1016/s0006-8993(01)02485-4
  16. Neni D. Pengaruh pemberian Zinc pada pasien tuberkulosis kasus baru dengan terapi etambutol terhadap lapang pandang. Universitas airlangga. 2015;
  17. Rindawati. Pengaruh pemberian zinc terhadap nilai sensitivitas sontras pada penderita tuberkulosis yang mendapat etambutol. Fakultas Kedokteran Universitas Andalas. 2010;
  18. Yulianti SR. Efek suplementasi ion zinc pada pengobatan tuberkulosis paru terhadap perubahan p100 latensi VEP. . Fakultas Kedokteran Universitas Indonesia. 2006;
  19. Chamberlain PD, Sadaka A, Berry S, Lee AG. Ethambutol optic neuropathy. Curr Opin Ophthalmol. 2017 Nov;28(6):545–51. DOI: 10.1097/ICU.0000000000000416
  20. Hao Q, Xiao X, Zhen J, Feng J, Song C, Jiang B, et al. Resveratrol attenuates acute kidney injury by inhibiting death receptor-mediated apoptotic pathways in a cisplatin-induced rat model. Mol Med Rep. 2016 Oct;14(4):3683–9. DOI: 10.3892/mmr.2016.5714
  21. Mandal S, Saxena R, Dhiman R, Mohan A, Padhy SK, Phuljhele S, et al. Prospective study to evaluate incidence and indicators for early detection of ethambutol toxicity. British Journal of Ophthalmology. 2021 Jul;105(7):1024–8. DOI: 10.1136/bjophthalmol-2020-316897
  22. Yan Sheng W, Ya Sui L, Ge W, Qing Wu S, Zhu LW. Analysis of structural injury pattern in peripapillary retinal nerve fibre layer and retinal ganglion cell layer in ethambutol- induced optic neuropathy. BMC ophtalmology. 2021;1–8. DOI: 10.1186/s12886-021-01881-y
  23. Koul P. Ocular toxicity with ethambutol therapy: Timely recaution. Lung India. 2015;32(1):1. doi: 10.4103/0970-2113.148395
  24. Ghulam H, Kadri SM, Manzoor A, Waseem Q, Aatif MS, Khan GQ, et al. Status of zinc in pulmonary tuberculosis. The Journal of Infection in Developing Countries. 2009 Jun 1;3(05). DOI: 10.3855/jidc.244
  25. Fitriyah N, Kusidantoro, Mauthia N, Suhendro G, Agustini L. Effek suplementasi zn terhadap ketebalan retinal nerve fiber layer pada pasien TB paru yang diberikan etambutol. . ADLN_Univ Airlangga. 2017;
  26. Yudapratiwi N, Enus S, Setiohadji B, Hernowo BS. Suplementasi zinc dan densitas ganglion retina tikus yang diberi etambutol. Bandung Med Jour. 2012;4:1–18

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