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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

Authors

Ekramy Elmorsy

Ayat Al-Ghafari

Amal Misbah Aggour

Soaad Mohamed Mosad

Raheela Khan

Saad Amer



Abstract

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.

Journal Article Type Article
Publication Date Apr 15, 2017
Journal Toxicology Letters
Print ISSN 0378-4274
Electronic ISSN 1879-3169
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 272
APA6 Citation Elmorsy, E., Al-Ghafari, A., Aggour, A. M., Mosad, S. M., Khan, R., & Amer, S. (2017). Effect of antipsychotics on mitochondrial bioenergetics of rat ovarian theca cells. Toxicology Letters, 272, doi:10.1016/j.toxlet.2017.03.018
DOI https://doi.org/10.1016/j.toxlet.2017.03.018
Keywords Antipsychotics; Ovarian cytotoxicity; Mitochondrial bioenergetics; Reproductive toxicity
Publisher URL http://www.sciencedirect.com/science/article/pii/S0378427417301200
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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