Effect of antipsychotics on mitochondrial bioenergetics of rat ovarian theca cells

Elmorsy, Ekramy; Al‐Ghafari, Ayat B.; Aggour, Amal Misbah; Mosad, Soaad Mohamed; Khan, Raheela; Amer, Saad

doi:10.1016/j.toxlet.2017.03.018

Cited by 21 publications

(14 citation statements)

References 42 publications

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“…After 48 h, ovaries were harvested for isolation of the GCs and TCs following anaesthesia with 5% chloral hydrate. Cell debris in the GCs was removed using 70-μm cell strainers, and debris in TCs was removed using 100-μm cell strainers [30,31]. The primary GCs and TCs were cultured in Dulbecco's modified Eagle's medium/nutrient mixture F-12 (DMEM-F12) containing 10% fetal bovine serum (FBS, Wisent, Canada) and 1% penicillin-streptomycin solution (Gibco, USA) in 6-well (1 × 10 6 /well) or 12-well culture plates (1 × 10 5 /well), (adherent growth on the round coverslip), in a 5% CO 2 /air atmosphere and maintained at 37 °C.…”

Section: Isolation and Culture Of Granulosa Cells (Gc) And Theca Cellmentioning

confidence: 99%

Suppression of p66Shc prevents hyperandrogenism-induced ovarian oxidative stress and fibrosis

Wang

et al. 2020

J Transl Med

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Background: Rats with hyperandrogen-induced polycystic ovary syndrome (PCOS) have been shown to develop ovarian oxidative stress (OS) and fibrosis. The Sirt1 agonist, resveratrol, can reduce OS through inhibiting p66Shc in other models of OS. Methods: We created a rat PCOS model with increased OS levels following treatment with one of the two androgens, dehydroepiandrosterone (DHEA) and dihydrotestosterone (DHT). The PCOS related features were determined by measurement of malondialdehyde (MDA) and superoxide dismutase (SOD) levels or by examining the reactive oxygen species (ROS) levels using the DCF-DA probe. The potential mechanisms by which p66Shc/Sirt1 mediates ovarian fibrosis were explored by western blotting, quantitative reverse transcription-PCR, immunofluorescence staining, and immunohistochemistry. Results: Hyperandrogen dramatically augmented OS and activation of fibrotic factors in the ovary. Our data demonstrated that treatment with resveratrol enhanced Sirt1 and decreased ovarian OS as well as inhibited phosphorylation of p66Shc both in vivo and in vitro. The treatment suppressed fibrotic factor activation and improved ovarian morphology. Lentivirus-or siRNA-mediated p66Shc knockdown resulted in a dramatic enhancement of Sirt1 expression, down-regulation of ROS and suppression of fibrotic factors in granulosa cells. Moreover, p66Shc overexpression markedly increased the expression of fibrotic factors. Additionally, silencing Sirt1 induced a dramatic increase in p66Shc and enhanced activation of fibrotic factors. Conclusions: p66Shc may be a direct target of Sirt1 for inducing ROS and thus promoting fibrosis. Further exploration of the mechanisms of p66Shc in both fibrosis and OS may provide novel therapeutic strategies that will facilitate the improvement in PCOS symptoms and reproductive functions.

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Section: Isolation and Culture Of Granulosa Cells (Gc) And Theca Cellmentioning

confidence: 99%

Suppression of p66Shc prevents hyperandrogenism-induced ovarian oxidative stress and fibrosis

Wang

et al. 2020

J Transl Med

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“…Risperidone does not require regular clinical monitoring of white blood cell (WBC) count; however, anecdotal evidence has shown that it could modify and reduce the leukocyte count. Different risperidone doses (2-4 mg/day) and the combined treatment of risperidone/paliperidone (2 mg/day/100 mg) caused leukopenia with neutropenia (155) or lymphopenia (153,(156)(157)(158) as well as fever (159). Other leukocyte alterations have been described.…”

Section: Risperidonementioning

confidence: 99%

Immunoendocrine Peripheral Effects Induced by Atypical Antipsychotics

et al. 2020

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Atypical antipsychotics (AAP) or second-generation antipsychotics are the clinical option for schizophrenia treatment during acute psychoses, but they are also indicated for maintenance during lifetime, even though they are being used for other psychiatric conditions in clinical practice such as affective disorders and autism spectrum disorder, among others. These drugs are differentiated from typical antipsychotics based on their clinical profile and are a better choice because they cause fewer side effects regarding extrapyramidal symptoms (EPS). Even though they provide clear therapeutic benefits, AAP induce peripheral effects that trigger phenotypic, functional, and systemic changes outside the Central Nervous System (CNS). Metabolic disease is frequently associated with AAP and significantly impacts the patient's quality of life. However, other peripheral changes of clinical relevance are present during AAP treatment, such as alterations in the immune and endocrine systems as well as the intestinal microbiome. These less studied alterations also have a significant impact in the patient's health status. This manuscript aims to revise the peripheral immunological, endocrine, and intestinal microbiome changes induced by AAP consumption recommended in the clinical guidelines for schizophrenia and other psychiatric disorders.

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“…48 Furthermore, CPZ, HAL, CLZ and RIS were found to disrupt the mitochondrial functions of blood-brain microvascular endothelial cells and ovarian theca cells. 26,49 The effect of APs on intracellular ATP was previously reported in many in vivo and in vitro studies. Vairetti et al reported a significant decrease in ATP content in the cerebellum, the striatum and the cortex of HAL-treated rats.…”

Section: Discussionmentioning

confidence: 88%

“…Some side effects of APs may be associated with mitochondrial dysfunction, which is considered to be involved in the development of AP‐induced side and toxic effects, such as extrapyramidal manifestations and menstrual irregularities 25,26 . Thus, this work aimed to investigate the role of bioenergetics disruption in AP‐induced DM using the isolated pancreatic primary cell line of the CD1 mouse as a model.…”

Section: Introductionmentioning

confidence: 99%

“…24 Some side effects of APs may be associated with mitochondrial dysfunction, which is considered to be involved in the development of AP-induced side and toxic effects, such as extrapyramidal manifestations and menstrual irregularities. 25,26 Thus, this work aimed to investigate the role of bioenergetics disruption in AP-induced DM using the isolated pancreatic primary cell line of the CD1 mouse as a model. The effects of commonly used APs, namely chlorpromazine (CPZ), haloperidol (HAL) and clozapine (CLZ), on the mitochondrial bioenergetics of isolated mouse cells were evaluated using different functional and structural assays.…”

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confidence: 99%

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Antipsychotics inhibit the mitochondrial bioenergetics of pancreatic beta cells isolated from CD1 mice

Elmorsy

Alelwani

Kattan

et al. 2020

Basic Clin Pharma Tox

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Antipsychotics (APs) are mainly used as long-term medications for many psychiatric conditions, such as schizophrenia, bipolar disorder and Alzheimer's disease. 1,2 The number of individuals receiving APs worldwide is surprisingly high. 3 APs are classified as either old typical (conventional) or newer atypical APs with different common side effects, including extrapyramidal manifestations, 4 atropine-like action 5 and metabolic disorders. 6 Since the mid-1960s, AP treatment was associated with the aggravation of already existing DM or the development of new-onset type II DM with reported higher risk of hyperglycaemic emergencies. 7-12

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Effect of antipsychotics on mitochondrial bioenergetics of rat ovarian theca cells

Cited by 21 publications

References 42 publications

Suppression of p66Shc prevents hyperandrogenism-induced ovarian oxidative stress and fibrosis

Suppression of p66Shc prevents hyperandrogenism-induced ovarian oxidative stress and fibrosis

Immunoendocrine Peripheral Effects Induced by Atypical Antipsychotics

Antipsychotics inhibit the mitochondrial bioenergetics of pancreatic beta cells isolated from CD1 mice

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