A new approach on lithium-induced neurotoxicity using rat neuronal cortical culture: Involvement of oxidative stress and lysosomal/mitochondrial toxic Cross-Talk

Author:

Yousefsani Bahareh Sadat12,Askian Romina3,Pourahmad Jalal3

Affiliation:

1. Research Institute for Islamic and Complementary Medicine, Iran University of Medical Sciences , Tehran , Iran

2. School of Persian Medicine, Iran University of Medical Sciences , Tehran , Iran

3. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences , Tehran , Iran

Abstract

Abstract Lithium (Li) is a widely-used medication for the treatment of patients with bipolar disorder. Li causes different complications. One of the most important adverse effects of Li is neurotoxicity. Neurotoxicity is usually irreversible which may lead to very important complications. The symptoms of Li-induced neurotoxicity include tremor, delirium, seizures, coma, and death. In this study, we wanted to evaluate the exact sub-cellular mechanisms of Li-induced neurotoxicity. For this purpose, we used primary neuronal cortical culture for investigating lithium-induced neurotoxicity. We applied the postnatal rat pups for isolating the cortical neurons. After that, we evaluated neural viability, neural reactive oxygen specious (ROS), lipid peroxidation, mitochondrial membrane potential (MMP), lysosomal membrane integrity (LMI), and reduced (GSH) and oxidized (GSSG) glutathione. Our results demonstrated that the cytotoxic effect of Li has mediated through lysosomal membrane leakage associated with ROS formation and reduction of MMP. Furthermore, the incubation of isolated neurons with Li caused rapid GSH depletion (as GSSG efflux) as another marker of cellular oxidative stress. We concluded that Li causes neurotoxicity in a dose-dependent manner. Besides, Li-induced neurotoxicity is a result of the generation of ROS and LP, which leads to mitochondrial/lysosomal toxic cross-talk.

Publisher

Walter de Gruyter GmbH

Subject

Materials Chemistry,Metals and Alloys,Condensed Matter Physics,General Chemistry

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