Repeated Administration of Mercury Accelerates Progression of Multiple Sclerosis through Mitochondrial Dysfunction

Document Type: Research article

Authors

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

2 Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Science, Ardabil, Iran.

3 Students research committee, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

4 Department of Toxicology and Pharmacology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences

5 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Ira.

Abstract

Multiple Sclerosis (MS) is a neurodegenerative and autoimmune disease that it’s molecular etiology and factors involving in its progression remains unknown. In this study for evaluation effect of mercuric on progression of MS we investigated the additive effect of mercuric sulfide on the brain mitochondrial dysfunction in experimental autoimmune encephalomyelitis (EAE) model of MS in C57BL/6 mice. EAE model of MS induced by injecting myelin oligodendrocyte glycoprotein (MOG) to female C57BL/6 mice. Neurobehavioral alterations are observed and recorded in the test animals. Experimental animals are divided into four groups (n=8); control, Hg2+, EAE, EAE with Hg2+. Mice were sacrificed by cervical dislocation at day 28 and brain mitochondria were isolated and mitochondrial toxicity parameters including mitochondrial swelling, reactive oxygen species (ROS) formation, collapse of mitochondrial membrane potential (MMP) and cytochrome c release were measured. Our results showed that repeated treatment of mercury following induction of EAE in mice significantly increased the neurobehavioral scores, as well as mitochondrial toxicity through ROS formation, mitochondrial swelling, collapse of MMP and cytochrome c release in brain mitochondria. Our findings proved that repeated exposure with mercury accelerates progression of MS through mitochondrial damage related to oxidative stress and finally apoptosis in brain mitochondria in MS.

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