Role of oxidative stress in antituberculous drugs (individuals and combined) cytotoxicity in HepG2 cells

Hepatotoxicity is a common side and toxic effect of Antituberculous (Anti-TB) drugs with reported higher incidence with anti-TB combinations. Oxidative stress was shown to have a role. This study examined oxidative stress effects of the first line Anti-TB drugs; Rifampicin (RIF), isoniazid (INH) a...

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Main Authors:	Elmorsy, Ekramy, Attalla, Sohayla M., Al-Ghafari, Ayat, Nwidu, Lucky Legbosi
Format:	Article
Language:	English
Published:	Malaysian Society of Applied Biology 2016
Online Access:	http://journalarticle.ukm.my/11828/ http://journalarticle.ukm.my/11828/ http://journalarticle.ukm.my/11828/1/45_02_23.pdf

id	ukm-11828
recordtype	eprints
spelling	ukm-118282018-07-02T03:58:22Z http://journalarticle.ukm.my/11828/ Role of oxidative stress in antituberculous drugs (individuals and combined) cytotoxicity in HepG2 cells Elmorsy, Ekramy Attalla, Sohayla M. Al-Ghafari, Ayat Nwidu, Lucky Legbosi Hepatotoxicity is a common side and toxic effect of Antituberculous (Anti-TB) drugs with reported higher incidence with anti-TB combinations. Oxidative stress was shown to have a role. This study examined oxidative stress effects of the first line Anti-TB drugs; Rifampicin (RIF), isoniazid (INH) and pyrazinamide PZA (individually and combined) on HepG2 cells. MTT assay (3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) was used to study the cytotoxic effect of the tested Anti-TB drugs. The effect of anti-TB drugs on total glutathione HepG2 cells and the production of reactive oxygen species (ROSs) were studied (individually and in combinations). Furthermore, the protective effect of the antioxidant reduced glutathione was assayed. The data revealed that the tested anti-TB were cytotoxic to HepG2 cells. RIF was the most potent. The tested drugs in their estimated IC50s, to different extents, enhanced significantly (P<0.0001) ROSs production and decreased total glutathione (P <0.0001). Furthermore, 48 hours pre-treatment with INH (3mM) significantly increased ROS production and decreased glutathione with RIF (0.1mM) (P <0.01 and P <0.05 respectively) and PZA (10 mM) (P <0.01 and P <0.05 respectively). Combined RIF (0.1mM) and INH (3mM) significantly decreased total glutathione (P<0.05 for each) and increased ROSs production (P<0.05) in HepG2 cells (P<0.05 for each). Interestingly, reduced glutathione (GSH) significantly decreased the cytotoxicity of RIF and INH (P=0.005 and 0.015, respectively). These data showed that oxidative stress play a crucial role in anti-TB induced hepatotoxicity, which can be alleviated by inclusion of antioxidant in therapy, though there is need of clinical trials. Moreover, combined anti-TB therapy should be considered as a risk factor with any other oxidative liver injuries. Malaysian Society of Applied Biology 2016-12 Article PeerReviewed application/pdf en http://journalarticle.ukm.my/11828/1/45_02_23.pdf Elmorsy, Ekramy and Attalla, Sohayla M. and Al-Ghafari, Ayat and Nwidu, Lucky Legbosi (2016) Role of oxidative stress in antituberculous drugs (individuals and combined) cytotoxicity in HepG2 cells. Malaysian Applied Biology, 45 (2). pp. 151-158. ISSN 0126-8643 http://www.mabjournal.com/index.php?option=com_content&view=article&id=565&catid=59:current-view&Itemid=56
repository_type	Digital Repository
institution_category	Local University
institution	Universiti Kebangasaan Malaysia
building	UKM Institutional Repository
collection	Online Access
language	English
description	Hepatotoxicity is a common side and toxic effect of Antituberculous (Anti-TB) drugs with reported higher incidence with anti-TB combinations. Oxidative stress was shown to have a role. This study examined oxidative stress effects of the first line Anti-TB drugs; Rifampicin (RIF), isoniazid (INH) and pyrazinamide PZA (individually and combined) on HepG2 cells. MTT assay (3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) was used to study the cytotoxic effect of the tested Anti-TB drugs. The effect of anti-TB drugs on total glutathione HepG2 cells and the production of reactive oxygen species (ROSs) were studied (individually and in combinations). Furthermore, the protective effect of the antioxidant reduced glutathione was assayed. The data revealed that the tested anti-TB were cytotoxic to HepG2 cells. RIF was the most potent. The tested drugs in their estimated IC50s, to different extents, enhanced significantly (P<0.0001) ROSs production and decreased total glutathione (P <0.0001). Furthermore, 48 hours pre-treatment with INH (3mM) significantly increased ROS production and decreased glutathione with RIF (0.1mM) (P <0.01 and P <0.05 respectively) and PZA (10 mM) (P <0.01 and P <0.05 respectively). Combined RIF (0.1mM) and INH (3mM) significantly decreased total glutathione (P<0.05 for each) and increased ROSs production (P<0.05) in HepG2 cells (P<0.05 for each). Interestingly, reduced glutathione (GSH) significantly decreased the cytotoxicity of RIF and INH (P=0.005 and 0.015, respectively). These data showed that oxidative stress play a crucial role in anti-TB induced hepatotoxicity, which can be alleviated by inclusion of antioxidant in therapy, though there is need of clinical trials. Moreover, combined anti-TB therapy should be considered as a risk factor with any other oxidative liver injuries.
format	Article
author	Elmorsy, Ekramy Attalla, Sohayla M. Al-Ghafari, Ayat Nwidu, Lucky Legbosi
spellingShingle	Elmorsy, Ekramy Attalla, Sohayla M. Al-Ghafari, Ayat Nwidu, Lucky Legbosi Role of oxidative stress in antituberculous drugs (individuals and combined) cytotoxicity in HepG2 cells
author_facet	Elmorsy, Ekramy Attalla, Sohayla M. Al-Ghafari, Ayat Nwidu, Lucky Legbosi
author_sort	Elmorsy, Ekramy
title	Role of oxidative stress in antituberculous drugs (individuals and combined) cytotoxicity in HepG2 cells
title_short	Role of oxidative stress in antituberculous drugs (individuals and combined) cytotoxicity in HepG2 cells
title_full	Role of oxidative stress in antituberculous drugs (individuals and combined) cytotoxicity in HepG2 cells
title_fullStr	Role of oxidative stress in antituberculous drugs (individuals and combined) cytotoxicity in HepG2 cells
title_full_unstemmed	Role of oxidative stress in antituberculous drugs (individuals and combined) cytotoxicity in HepG2 cells
title_sort	role of oxidative stress in antituberculous drugs (individuals and combined) cytotoxicity in hepg2 cells
publisher	Malaysian Society of Applied Biology
publishDate	2016
url	http://journalarticle.ukm.my/11828/ http://journalarticle.ukm.my/11828/ http://journalarticle.ukm.my/11828/1/45_02_23.pdf
first_indexed	2023-09-18T20:01:14Z
last_indexed	2023-09-18T20:01:14Z
_version_	1777406862321254400

Role of oxidative stress in antituberculous drugs (individuals and combined) cytotoxicity in HepG2 cells

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