Research Journal of Pharmacy and Technology

Open Access Open Access  Restricted Access Subscription Access
Open Access Open Access Open Access  Restricted Access Restricted Access Subscription Access

Mechanism of Apoptosis Retinal Ganglion Cells Rattus Norvegicus Caused by Ethambutol


Affiliations
1 Department of Ophthalmology, Faculty of Medicine-Dr. Soetomo Teaching Hospital, Universitas Airlangga, Surabaya 60131,, Indonesia
2 Department of Pathology Clinic, Faculty of Medicine-Dr. Soetomo Teaching Hospital, Universitas Airlangga, Surabaya 60131,, Indonesia
3 Department of Anatomic Pathology, Faculty of Medicine-Dr. Soetomo Teaching Hospital, Universitas Airlangga, Surabaya 60131,, Indonesia
4 Department of Veterinary Anatomy, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya 60115,, Indonesia
5 Department of Physiology, Faculty of Medicine-Dr. Soetomo Teaching Hospital, Universitas Airlangga, Surabaya 60131, Indonesia
6 Faculty of Medicine, Universitas Diponegoro, Semarang 50275,, Indonesia
     

   Subscribe/Renew Journal


Background: The cause of cell death is thought to be due to the pathological apoptotic process in Retinal Ganglion Cells (RGCs), but how the exact mechanism of what is most influential is still not explained. Objective: This study aimed to explain the mechanism of RGCs apoptosis Rattus Norvegicus which is thought to underlie the occurrence of ethambutol toxic optic neuropathy. Methods: A total of 42 male, adult Rattus norvegicus Sprague-Dawley strains were divided into 6 groups with 3 control groups and 3 treatment groups in a randomized design with time series test. The treatment groups were given ethambutol 15 mg/kg/day for each group within 5, 10 and 15 days orally using a gauge.Expressions of SOD2, MDA, PKC δ, p53, Cyt c, Caspase 3 and apoptosis were examined by immunohistochemical methods. Results: Ethambutol affected significant decreased expression of SOD2 with p=0.002 in 5 days, p=0.013 in 10 days and p=0.018 in 15 days; significant increased MDA in 5 days with p=0.05, 10 days with p=0.017, 15 days with p=0.002; significant increased p53 in 5 days with p=0.012, 10 days with p=0.002, 15 days with p=0.001; significant increased Cyt c in 5 days with p=0.004, 10 days with p=0.001, 15 days with p=0.001; significant increased Caspase 3 in 5 days with p=0.001, 10 days with p=0.003, 15 days with p=0.001 and apoptosis in 5 days with p=0.001, 10 days with p=0.001, 15 days with p=0.001. Conclusion: The mechanism of apoptosis of RGCs caused by ethambutol was showed via decreased expression SOD2, increased expression of MDA, p 53, Cyt c, Caspase 3 andapoptosis. These biomarkers are essential to detect apoptosis as one of mechanism in cell death.

Keywords

Apoptosis, ethambutol, toxic, Rattus, mechanism, SOD2.
Subscription Login to verify subscription
User
Notifications
Font Size


  • Liu Y, Chen Y. Unusual Periventricular Hemorrhage as the Initial Manifestation of Central Nervous System Tuberculosis. World Neurosurgery. 2020; 142:371–4.

  • Organization WH. Health at a Glance: Asia/Pacific 2018 Measuring Progress towards Universal Health Coverage: Measuring Progress towards Universal Health Coverage. OECD Publishing; 2018.

  • Sasongko D, Hasan H. Factors affecting uric acid changes in pulmonary tuberculosis patients who received oral anti tuberculosis therapy during one month. Medico-Legal Update. 2020; 20(2):836–42.

  • Ijaz AAKH. Association Between Refractive Errors and Heterotropia: A Counter Check. Pakistan Journal of Ophthalmology. 2018; 34(2).

  • Indrayani IAS et al. Characteristics of ethambutol optic neuropathy on tuberculosis treatment in sanglah hospital denpasar. 2019

  • Yamada D et al. Ethambutol neutralizes lysosomes and causes lysosomal zinc accumulation. Biochemical and biophysical research communications. 2016; 471(1):109–16.

  • Rudyono J, Basuki M, Triyono EA. Diagnostic test of brief peripheral neuropathy screen as distal sensory polyneuropathy-HIV diagnostic tool. Indian Journal of Forensic Medicine and Toxicology. 2020; 14(2):1670–5.

  • Priyandani Y et al. Measurement of self-reported fixed-dose combination antituberculosis drugs therapy regimen. Indian Journal of Forensic Medicine and Toxicology. 2019; 13(4):781–5.

  • Matteo S, Anna A, Matteo B. Mycobacterium Chimaera: Clinical and medico-legal considerations starting from a case of sudden acoustic damage. Legal Medicine. 2020; 47.

  • Tsai RK et al. PKCδ-dependent signaling mediates ethambutol-induced toxic effects on human retinal pigment cells. Molecular Vision. 2011; 17:1564.

  • Cinici E et al. Gene expression and histopathological evaluation of thiamine pyrophosphate on optic neuropathy induced with ethambutol in rats. International journal of ophthalmology. 2016; 9(10):1390.

  • Heng JE et al. Ethambutol is toxic to retinal ganglion cells via an excitotoxic pathway. Investigative ophthalmology & visual science. 1999; 40(1):190–6.

  • Wilhelm H, Schiefer U. Optic disc signs and optic neuropathies. In: Clinical Neuro-Ophthalmology. Springer; 2007. p. 101–25.

  • Tandon R. Parsons’ Diseases of the Eye. Elsevier India; 2019.

  • Kumar V et al. Robbins and Cotran pathologic basis of disease, professional edition e-book. Elsevier health sciences; 2014. 16. Nakano H et al. Cellular FLICE-inhibitory protein regulates tissue homeostasis. In: Apoptotic and Non-apoptotic Cell Death. Springer; 2015. p. 119–41.

  • Makunyane P, Mathebula S. Update on ocular toxicity of ethambutol. African Vision and Eye Health. 2016; 75(1):1–4.


Abstract Views: 261

PDF Views: 0




  • Mechanism of Apoptosis Retinal Ganglion Cells Rattus Norvegicus Caused by Ethambutol

Abstract Views: 261  |  PDF Views: 0

Authors

Lukisiari Agustini
Department of Ophthalmology, Faculty of Medicine-Dr. Soetomo Teaching Hospital, Universitas Airlangga, Surabaya 60131,, Indonesia
Nurwasis
Department of Ophthalmology, Faculty of Medicine-Dr. Soetomo Teaching Hospital, Universitas Airlangga, Surabaya 60131,, Indonesia
Aryati
Department of Pathology Clinic, Faculty of Medicine-Dr. Soetomo Teaching Hospital, Universitas Airlangga, Surabaya 60131,, Indonesia
Gatut Suhendro
Department of Ophthalmology, Faculty of Medicine-Dr. Soetomo Teaching Hospital, Universitas Airlangga, Surabaya 60131,, Indonesia
I Ketut Sudiana
Department of Anatomic Pathology, Faculty of Medicine-Dr. Soetomo Teaching Hospital, Universitas Airlangga, Surabaya 60131,, Indonesia
Widjiati
Department of Veterinary Anatomy, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya 60115,, Indonesia
Bambang Purwanto
Department of Physiology, Faculty of Medicine-Dr. Soetomo Teaching Hospital, Universitas Airlangga, Surabaya 60131, Indonesia
Winarto
Faculty of Medicine, Universitas Diponegoro, Semarang 50275,, Indonesia

Abstract


Background: The cause of cell death is thought to be due to the pathological apoptotic process in Retinal Ganglion Cells (RGCs), but how the exact mechanism of what is most influential is still not explained. Objective: This study aimed to explain the mechanism of RGCs apoptosis Rattus Norvegicus which is thought to underlie the occurrence of ethambutol toxic optic neuropathy. Methods: A total of 42 male, adult Rattus norvegicus Sprague-Dawley strains were divided into 6 groups with 3 control groups and 3 treatment groups in a randomized design with time series test. The treatment groups were given ethambutol 15 mg/kg/day for each group within 5, 10 and 15 days orally using a gauge.Expressions of SOD2, MDA, PKC δ, p53, Cyt c, Caspase 3 and apoptosis were examined by immunohistochemical methods. Results: Ethambutol affected significant decreased expression of SOD2 with p=0.002 in 5 days, p=0.013 in 10 days and p=0.018 in 15 days; significant increased MDA in 5 days with p=0.05, 10 days with p=0.017, 15 days with p=0.002; significant increased p53 in 5 days with p=0.012, 10 days with p=0.002, 15 days with p=0.001; significant increased Cyt c in 5 days with p=0.004, 10 days with p=0.001, 15 days with p=0.001; significant increased Caspase 3 in 5 days with p=0.001, 10 days with p=0.003, 15 days with p=0.001 and apoptosis in 5 days with p=0.001, 10 days with p=0.001, 15 days with p=0.001. Conclusion: The mechanism of apoptosis of RGCs caused by ethambutol was showed via decreased expression SOD2, increased expression of MDA, p 53, Cyt c, Caspase 3 andapoptosis. These biomarkers are essential to detect apoptosis as one of mechanism in cell death.

Keywords


Apoptosis, ethambutol, toxic, Rattus, mechanism, SOD2.

References