The role of oxidative stress in antipsychotics induced ovarian toxicity
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) a...
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Elsevier
2017
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| Online Access: | https://eprints.nottingham.ac.uk/44235/ |
| _version_ | 1848796868683759616 |
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| author | Elmorsy, Ekramy Al-Ghafari, Ayat Aggour, Amal Misbah Khan, Raheela Amer, Saad A. |
| author_facet | Elmorsy, Ekramy Al-Ghafari, Ayat Aggour, Amal Misbah Khan, Raheela Amer, Saad A. |
| author_sort | Elmorsy, Ekramy |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:54:49Z |
| format | Article |
| id | nottingham-44235 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:54:49Z |
| publishDate | 2017 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-442352020-05-04T19:55:08Z https://eprints.nottingham.ac.uk/44235/ The role of oxidative stress in antipsychotics induced ovarian toxicity Elmorsy, Ekramy Al-Ghafari, Ayat Aggour, Amal Misbah Khan, Raheela Amer, Saad A. 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. Elsevier 2017-10 Article PeerReviewed Elmorsy, Ekramy, Al-Ghafari, Ayat, Aggour, Amal Misbah, Khan, Raheela and Amer, Saad A. (2017) The role of oxidative stress in antipsychotics induced ovarian toxicity. Toxicology in Vitro, 44 . pp. 190-195. ISSN 1879-3177 Antipsychotics; Oxidative stress; Reproductive toxicity; Antioxidants http://www.sciencedirect.com/science/article/pii/S0887233317301947 doi:10.1016/j.tiv.2017.07.008 doi:10.1016/j.tiv.2017.07.008 |
| spellingShingle | Antipsychotics; Oxidative stress; Reproductive toxicity; Antioxidants Elmorsy, Ekramy Al-Ghafari, Ayat Aggour, Amal Misbah Khan, Raheela Amer, Saad A. The role of oxidative stress in antipsychotics induced ovarian toxicity |
| title | The role of oxidative stress in antipsychotics induced ovarian toxicity |
| title_full | The role of oxidative stress in antipsychotics induced ovarian toxicity |
| title_fullStr | The role of oxidative stress in antipsychotics induced ovarian toxicity |
| title_full_unstemmed | The role of oxidative stress in antipsychotics induced ovarian toxicity |
| title_short | The role of oxidative stress in antipsychotics induced ovarian toxicity |
| title_sort | role of oxidative stress in antipsychotics induced ovarian toxicity |
| topic | Antipsychotics; Oxidative stress; Reproductive toxicity; Antioxidants |
| url | https://eprints.nottingham.ac.uk/44235/ https://eprints.nottingham.ac.uk/44235/ https://eprints.nottingham.ac.uk/44235/ |