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
Amal Misbah Aggour
Soaad Mohamed Mosad
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.
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.
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).
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|
|Peer Reviewed||Peer Reviewed|
|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|
|Keywords||Antipsychotics; Ovarian cytotoxicity; Mitochondrial bioenergetics; Reproductive toxicity|
|Copyright Statement||Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0|
Elmorsy_Amer_2017 Accepted article.pdf
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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