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. 2016 Fall;15(4):834-841.

Repeated Administration of Mercury Intensifies Brain Damage in Multiple Sclerosis through Mitochondrial Dysfunction

Farzad Kahrizi  1 , Ahmad Salimi  2 , Farshid Noorbakhsh  3 , Mehrdad Faizi  1 , Freshteh Mehri  1 , Parvaneh Naserzadeh  4 , Nima Naderi  1 , Jalal Pourahmad  1
Affiliations

Repeated Administration of Mercury Intensifies Brain Damage in Multiple Sclerosis through Mitochondrial Dysfunction

Farzad Kahrizi et al. Iran J Pharm Res. 2016 Fall.

Abstract

In this study we investigated the additive effect of mercury on the brain mitochondrial dysfunction in experimental autoimmune encephalomyelitis (EAE) model. Experimental animals (female C57BL/6 mice) are divided into four groups (n = 8); control, Hg, EAE, EAE with Hg. EAE model of MS induced by injecting myelin oligodendrocyte glycoprotein (MOG). Neurobehavioral alterations are recorded and then mice were sacrificed 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. Our findings proved that repeated exposure with mercury accelerates progression of MS through mitochondrial damage related to oxidative stress and finally apoptosis.

Keywords: Apoptosis; Brain mitochondria; EAE model; Mercury; Oxidative stress.

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Figures

Figure 1
Figure 1
Behavioral and neurological signs in mice experimental groups. Values were presented as score of signs as described in materials and methods (n = 8). ** represents P < 0.01 significant difference, *** represents P < 0.001 significant difference, compared to EAE induced mice group.
Figure 2
Figure 2
ROS formation. Exposure to mercury (Hg) intensified ROS formation in EAE + Hg group compared to EAE group. Values have been presented as percent ROS formation (n = 8). *** represents significant difference between control and EAE groups, also $$$ represents significant difference (P < 0.001) between EAE and EAE+Hg2+ groups
Figure 3
Figure 3
Decline of MMP. Decline of MMP significantly decreased in EAE + Hg group compared to EAE group. Values expressed as percent of MMP collapse (n = 8). *** represents significant difference between control and EAE groups, also $$$ represents significant difference (P < 0.001) between EAE and EAE + Hg groups
Figure 4
Figure 4
Mitochondrial swelling. Hg enhanced mitochondrial swelling in EAE + Hg group. Values have been presented as decreasing absorbance at 450 nm (n = 8). *** represents significant difference between control and EAE groups, also $$$ represents significant difference (P < 0.001) between EAE and EAE + Hg groups
Figure 5
Figure 5
Cytochrome c release. In EAE + Hg and EAE groups cytochrome c released. Values have been presented as mean ± SD (n = 8). *** represents significant difference (P < 0. 001) compared to EAE induced group. Also $$$ represents significant difference (P < 0. 001) between EAE + Hg and EAE groups
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References

    1. Gochfeld M. Cases of mercury exposure, bioavailability, and absorption. Ecotoxicol. Environ. Saf. 2003;56:174–9. - PubMed
    1. Hylander LD, Meili M. 500 years of mercury production: Global annual inventory by region until 2000 and associated emissions. Sci. Total Environ. 2003;304:13–27. - PubMed
    1. Moreau T, Coles A, Wing M, Isaacs J, Hale G, Waldmann H, Compston A. Transient increase in symptoms associated with cytokine release in patients with multiple sclerosis. Brain. 1996;119:225–38. - PubMed
    1. Rietberg MB, Brooks D, Uitdehaag BM, Kwakkel G. Exercise therapy for multiple sclerosis. The Cochrane Library. 2004 - PMC - PubMed
    1. Beal M. Aging, energy, and oxidative stress in neurodegenerative diseases. Restor. Neurol. Neurosci. 1996;3:180–1. - PubMed

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