Effect of antipsychotics on mitochondrial bioenergetics of rat ovarian theca cells
Background Antipsychotics (APs) are widely prescribed drugs, which are well known to cause reproductive adverse effects through mechanisms yet to be determined. The purpose of this study was to investigate the effect of antipsychotics on mitochondrial bioenergetics of rat ovarian theca cells as a...
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| Format: | Article |
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Elsevier
2017
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| Online Access: | https://eprints.nottingham.ac.uk/43217/ |
| _version_ | 1848796638173200384 |
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| author | Elmorsy, Ekramy Al-Ghafari, Ayat Aggour, Amal Misbah Mosad, Soaad Mohamed Khan, Raheela Amer, Saad |
| author_facet | Elmorsy, Ekramy Al-Ghafari, Ayat Aggour, Amal Misbah Mosad, Soaad Mohamed Khan, Raheela Amer, Saad |
| author_sort | Elmorsy, Ekramy |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Background
Antipsychotics (APs) are widely prescribed drugs, which are well known to cause reproductive adverse effects through mechanisms yet to be determined. The purpose of this study was to investigate the effect of antipsychotics on mitochondrial bioenergetics of rat ovarian theca cells as a possible mechanism of reproductive toxicity.
Methods
Isolated rat theca interstitial cells (TICs) were treated with two typical (chlorpromazine [CPZ] and haloperidol [HAL]) and two atypical APs (risperidone [RIS] and clozapine [CLZ]). The effects of these APs on TICs bioenergetics (ATP content, mitochondrial complexes I and III activities, oxygen consumption rates (OCRs), mitochondrial membrane potential (MPP) and lactate production) and on steroidogenesis (androstenedione and progesterone synthesis) were investigated.
Results
All APs resulted in a concentration-dependent decrease in the ATP content of TICs. All APs at their estimated IC50s (6 μM, 21 μM, 35 μM and 37 μM for CPZ, HAL, CLZ and RIS respectively) significantly decreased TICs OCRs (p < 0.0001), MPP (p < 0.0001) and significantly (p = 0.0003) inhibited mitochondrial complex I activity. Only typical APs inhibited complex III (p = 0.005). Also, APs at IC50s increased TICs lactate production to varying degrees. All APs used at their IC50s significantly inhibited progesterone (p = 0.0022) and androstenedione (p = 0.0027) production. Only CPZ was found to inhibit these hormones at the low concentration (1 μM).
Conclusion
All four antipsychotics seem to inhibit mitochondrial bioenergetics and steroidogenesis in rat’s ovarian theca cells. These findings support the hypothesis that APs-induced reproductive toxicity may be through mechanisms involving mitochondrial insult>. Further research is required to establish the link between APs-induced mitochondrial dysfunction and disordered steroidogenesis. |
| first_indexed | 2025-11-14T19:51:10Z |
| format | Article |
| id | nottingham-43217 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:51:10Z |
| publishDate | 2017 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-432172020-05-04T18:41:57Z https://eprints.nottingham.ac.uk/43217/ Effect of antipsychotics on mitochondrial bioenergetics of rat ovarian theca cells Elmorsy, Ekramy Al-Ghafari, Ayat Aggour, Amal Misbah Mosad, Soaad Mohamed Khan, Raheela Amer, Saad Background Antipsychotics (APs) are widely prescribed drugs, which are well known to cause reproductive adverse effects through mechanisms yet to be determined. The purpose of this study was to investigate the effect of antipsychotics on mitochondrial bioenergetics of rat ovarian theca cells as a possible mechanism of reproductive toxicity. Methods Isolated rat theca interstitial cells (TICs) were treated with two typical (chlorpromazine [CPZ] and haloperidol [HAL]) and two atypical APs (risperidone [RIS] and clozapine [CLZ]). The effects of these APs on TICs bioenergetics (ATP content, mitochondrial complexes I and III activities, oxygen consumption rates (OCRs), mitochondrial membrane potential (MPP) and lactate production) and on steroidogenesis (androstenedione and progesterone synthesis) were investigated. Results All APs resulted in a concentration-dependent decrease in the ATP content of TICs. All APs at their estimated IC50s (6 μM, 21 μM, 35 μM and 37 μM for CPZ, HAL, CLZ and RIS respectively) significantly decreased TICs OCRs (p < 0.0001), MPP (p < 0.0001) and significantly (p = 0.0003) inhibited mitochondrial complex I activity. Only typical APs inhibited complex III (p = 0.005). Also, APs at IC50s increased TICs lactate production to varying degrees. All APs used at their IC50s significantly inhibited progesterone (p = 0.0022) and androstenedione (p = 0.0027) production. Only CPZ was found to inhibit these hormones at the low concentration (1 μM). Conclusion All four antipsychotics seem to inhibit mitochondrial bioenergetics and steroidogenesis in rat’s ovarian theca cells. These findings support the hypothesis that APs-induced reproductive toxicity may be through mechanisms involving mitochondrial insult>. Further research is required to establish the link between APs-induced mitochondrial dysfunction and disordered steroidogenesis. Elsevier 2017-04-15 Article PeerReviewed Elmorsy, Ekramy, Al-Ghafari, Ayat, Aggour, Amal Misbah, Mosad, Soaad Mohamed, Khan, Raheela and Amer, Saad (2017) Effect of antipsychotics on mitochondrial bioenergetics of rat ovarian theca cells. Toxicology Letters, 272 . pp. 94-100. ISSN 1879-3169 Antipsychotics; Ovarian cytotoxicity; Mitochondrial bioenergetics; Reproductive toxicity http://www.sciencedirect.com/science/article/pii/S0378427417301200 doi:10.1016/j.toxlet.2017.03.018 doi:10.1016/j.toxlet.2017.03.018 |
| spellingShingle | Antipsychotics; Ovarian cytotoxicity; Mitochondrial bioenergetics; Reproductive toxicity Elmorsy, Ekramy Al-Ghafari, Ayat Aggour, Amal Misbah Mosad, Soaad Mohamed Khan, Raheela Amer, Saad Effect of antipsychotics on mitochondrial bioenergetics of rat ovarian theca cells |
| title | Effect of antipsychotics on mitochondrial bioenergetics of rat ovarian theca cells |
| title_full | Effect of antipsychotics on mitochondrial bioenergetics of rat ovarian theca cells |
| title_fullStr | Effect of antipsychotics on mitochondrial bioenergetics of rat ovarian theca cells |
| title_full_unstemmed | Effect of antipsychotics on mitochondrial bioenergetics of rat ovarian theca cells |
| title_short | Effect of antipsychotics on mitochondrial bioenergetics of rat ovarian theca cells |
| title_sort | effect of antipsychotics on mitochondrial bioenergetics of rat ovarian theca cells |
| topic | Antipsychotics; Ovarian cytotoxicity; Mitochondrial bioenergetics; Reproductive toxicity |
| url | https://eprints.nottingham.ac.uk/43217/ https://eprints.nottingham.ac.uk/43217/ https://eprints.nottingham.ac.uk/43217/ |