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Antidepressants are cytotoxic to rat primary blood brain barrier endothelial cells at high therapeutic concentrations.
Elmorsy, Ekramy; Al-Ghafari, Ayat; Almutairi, Fahd M; Aggour, Amal Misbah; Carter, Wayne G.
Affiliation
  • Elmorsy E; Departments of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Mansoura University, Egypt; Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia. Electronic address: ekramyelmorsy@mans.edu.eg.
  • Al-Ghafari A; Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia. Electronic address: abalghafari@kau.edu.sa.
  • Almutairi FM; Department of Biochemistry, Faculty of Science, University of Tabuk, Saudi Arabia. Electronic address: falrabae@ut.edu.sa.
  • Aggour AM; Clinical Pathology, Ministry of Health, Egypt.
  • Carter WG; School of Medicine, University of Nottingham, Royal Derby Hospital Centre, Derby, UK. Electronic address: wayne.carter@nottingham.ac.uk.
Toxicol In Vitro ; 44: 154-163, 2017 Oct.
Article in En | MEDLINE | ID: mdl-28712878
Antidepressants are commonly employed for the treatment of major depressive disorders and other psychiatric conditions. We investigated the relatively acute cytotoxic effects of three commonly prescribed antidepressants: fluoxetine, sertraline, and clomipramine on rat primary blood brain barrier endothelial cells over a concentration range of 0.1-100µM. At therapeutic concentrations (0.1µM) no significant cytotoxicity was observed after 4, 24, or 48h. At high therapeutic to overdose concentrations (1-100µM), antidepressants reduced cell viability in proportion to their concentration and exposure duration. At 1µM, antidepressants significantly reduced mitochondrial membrane potential. At drug concentrations producing ~50% inhibition of cell viability, all drugs significantly reduced cellular oxygen consumption rates, activities of mitochondrial complexes I and III, and triggered a significant increase of lactate production. Fluoxetine (6.5µM) and clomipramine (5.5µM) also significantly lowered transcellular transport of albumin. The mechanism of cellular cytotoxicity was evaluated and at high concentrations all drugs significantly increased the production of reactive oxygen species, and significantly increased the activity of the pro-apoptotic caspases-3, 8, and 9. Comet assays revealed that all drugs were genotoxic. Pre-incubation of cells with glutathione significantly ameliorated antidepressant-induced cytotoxicity, indicating the potential benefit of treatment of overdosed patients with antioxidants.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Fluoxetine / Clomipramine / Sertraline / Endothelial Cells / Antidepressive Agents Limits: Animals Language: En Journal: Toxicol In Vitro Journal subject: TOXICOLOGIA Year: 2017 Document type: Article Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Fluoxetine / Clomipramine / Sertraline / Endothelial Cells / Antidepressive Agents Limits: Animals Language: En Journal: Toxicol In Vitro Journal subject: TOXICOLOGIA Year: 2017 Document type: Article Country of publication: