Neuroprotective Effect of Diphenyl Diselenide in a Experimental Stroke Model: Maintenance of Redox System in Mitochondria of Brain Regions

Abstract

Acute stroke is a major risk for morbidity and mortality in aging population. Mitochondrion has been the focus of a wide stroke-related research. This study investigated if treatment or pre-treatment with diphenyl diselenide (PhSe)2 can prevent mitochondrial damage in cerebral structures of rats induced by an ischemia and reperfusion (I/R) model. Adult male Wistar rats were assigned into five experimental groups: sham operation, ischemia/reperfusion, pre-treated + I/R, treated + I/R, and Sham + (PhSe)2. Neurological score showed the damage caused by I/R, which was partially prevented by (PhSe)2. Moreover, mitochondria of hippocampus and cortex were impaired by I/R through an increase of reactive oxygen species production, mitochondrial membrane potential (ΔΨm) and electrons flow alteration, activity of complex I deregulation as well as mitochondrial swelling. However, the ischemic damage did not induce an increase in pro-apoptotic proteins expression, but demonstrated an enhanced expression of Hsp70. The mitochondrial redox state was also altered (GSH/GSSG ratio, MnSOD, and GPx activities). Our results revealed that all treatments with (PhSe)2 significantly reduced the mitochondrial damage induced by I/R. These findings suggest that neuroprotective properties of (PhSe)2 may be attributed to the maintenance of mitochondrial redox balance.

Diphenyl diselenide protects neuronal cells against oxidative stress and mitochondrial dysfunction: Involvement of the glutathione-dependent antioxidant system

“…By contrast, the pre-incubation of cells with a nontoxic concentration of (PhSe) 2 rendered cells more efficient in detoxifying tert-BuOOH (or derived oxidants), which in turn prevented the cell death, showing that these cells can cope better with pro-oxidant situations. This in vitro observation can better explain the neuroprotective effect of (PhSe) 2 previously described in in vivo models of neurodegenerative diseases, such as Alzheimer disease (AD) [11] and neurotoxicity (CdCl 2 , H 2 O 2 , methimazole, and ischemia/reperfusion) [43] , [44] , [45] , [46] .…”

(p-ClPhSe)2Reduces Hepatotoxicity Induced by Monosodium Glutamate by Improving Mitochondrial Function in Rats

“…In fact, the mitochondrial Δψm, swelling, the ROS production and activity of MnSOD were modulated by treatment with ( p ‐ClPhSe) 2 in rats. In agreement with these results, it has been shown that organoselenium compounds improved the mitochondrial redox balance [Carvalho et al, ; Dobrachinski et al, ]. Moreover, in healthy mitochondria, MnSOD dismutates superoxide anions generated as a byproduct of the electron transport chain to the strong oxidant hydrogen peroxide (H 2 O 2 ), which is subsequently transformed into water by catalase, glutathione peroxidase, peroxiredoxin, or thioredoxins [Vincent and Taylor, ].…”

Diphenyl Diselenide Modulates Gene Expression of Antioxidant Enzymes in the Cerebral Cortex, Hippocampus and Striatum of Female Hypothyroid Rats

“…The neuroprotective effects of diphenyl diselenide have been linked to its antioxidant properties [52,55,75,76]. Considering that antioxidant defense parameters are influenced by thyroid hormones and Se status, the present work investigated whether the neuroprotection offered by diphenyl diselenide intake in a hypothyroidism state could be associated with modulation of mRNA expression of brain antioxidant enzymes.…”