Effect of antipsychotics on mitochondrial bioenergetics of rat ovarian theca cells

Elmorsy, Ekramy and Al-Ghafari, Ayat and Aggour, Amal Misbah and Mosad, Soaad Mohamed and 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

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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.

Item Type: Article
Keywords: Antipsychotics; Ovarian cytotoxicity; Mitochondrial bioenergetics; Reproductive toxicity
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine
Identification Number: 10.1016/j.toxlet.2017.03.018
Depositing User: Eprints, Support
Date Deposited: 25 May 2017 07:59
Last Modified: 25 May 2017 07:59
URI: http://eprints.nottingham.ac.uk/id/eprint/43217

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