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The role of oxidative stress in antipsychotics induced ovarian toxicity

Elmorsy, Ekramy; Al-Ghafari, Ayat; Aggour, Amal Misbah; Khan, Raheela; Amer, Saad A.

Authors

Ekramy Elmorsy

Ayat Al-Ghafari

Amal Misbah Aggour

RAHEELA KHAN RAHEELA.KHAN@NOTTINGHAM.AC.UK
Professor of Cellular Physiology

SAAD AMER saad.amer@nottingham.ac.uk
Clinical Associate Professor



Abstract

This study tested the hypothesis that oxidative stress could be an underlying mechanism for APs-induced ovarian cytotoxicity and reproductive dysfunction. Rat ovarian theca interstitial cells (TICs) were isolated and treated with four APs [chlorpromazine (CPZ), haloperidol (HAL), risperidone (RIS) and clozapine (CLZ)]. MTT assay was used to test the effects of these antipsychotics on TICs viability and to estimate their 50% inhibitory concentrations (IC50s). The effects of APs (IC50s and 1 μM concentrations) on the activities of caspases-3, -8 and -9, reactive oxygen species (ROS) production, total intracellular glutathione and lipid peroxidation (LPO) in TICs were assessed. The effect of antioxidants (reduced glutathione (GSH) and quercetin) on the APs-induced cytotoxicity on TICs was investigated. MTT assay showed all APs to reduce TICs viability. CPZ, HAL and CLZ significantly increased the activity of caspases-3, -8 and -9 (P < 0.0001, < 0.0001 and < 0.01, respectively). All APs at IC50s significantly (P < 0.0001) increased ROS production, decreased total intracellular glutathione and increased LPO. MTT assay in the presence of antioxidants (reduced GSH (5 mM) or quercetin (50 mM)) showed each antioxidant to significantly inhibit the effects of APs at their IC50s on TICs viability. In conclusion, oxidative stress seems to be a possible mechanism for APs-induced ovarian and reproductive toxicity.

Citation

Elmorsy, E., Al-Ghafari, A., Aggour, A. M., Khan, R., & Amer, S. A. (2017). The role of oxidative stress in antipsychotics induced ovarian toxicity. Toxicology in Vitro, 44, https://doi.org/10.1016/j.tiv.2017.07.008

Journal Article Type Article
Acceptance Date Jul 12, 2017
Online Publication Date Jul 13, 2017
Publication Date Oct 1, 2017
Deposit Date Jul 17, 2017
Publicly Available Date Jul 17, 2017
Journal Toxicology in Vitro
Print ISSN 0887-2333
Electronic ISSN 1879-3177
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 44
DOI https://doi.org/10.1016/j.tiv.2017.07.008
Keywords Antipsychotics; Oxidative stress; Reproductive toxicity; Antioxidants
Public URL http://eprints.nottingham.ac.uk/id/eprint/44235
Publisher URL http://www.sciencedirect.com/science/article/pii/S0887233317301947
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0





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