The role of oxidative stress in antipsychotics induced ovarian toxicity

• Published in: Toxicology in vitro 2017-10, Vol.44, p.190-195
• Main Authors: Elmorsy, Ekramy, Al-Ghafari, Ayat, Aggour, Amal Misbah, Khan, Raheela, Amer, Saad
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants; Antipsychotic Agents - toxicity; Antipsychotics; Assaying; Caspases - metabolism; Cell Survival - drug effects; Cells, Cultured; Chlorpromazine; Chlorpromazine - toxicity; Clozapine; Clozapine - toxicity; Cytotoxicity; Drugs; Female; Glutathione; Glutathione - metabolism; Haloperidol; Haloperidol - toxicity; Interstitial cells; Intracellular; Lipid peroxidation; Ovarian cancer; Oxidative stress; Oxidative Stress - drug effects; Peroxidation; Quercetin; Rats, Sprague-Dawley; Reactive oxygen species; Reactive Oxygen Species - metabolism; Reproductive system; Reproductive toxicity; Risperidone; Risperidone - toxicity; Theca; Theca Cells - drug effects; Theca Cells - metabolism; Toxicity testing; Viability
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2017.07.008

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 1μM 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