Protective effects of diphenyl diselenide in a mouse model of brain toxicity

Abstract

Interest in organoselenide chemistry and biochemistry has increased in the past three decades, mainly due to their chemical and biological activities. Here, we investigated the protective effect of the organic selenium compound diphenyl diselenide (PhSe)2 (5 μmol/kg), in a mouse model of methylmercury (MeHg)-induced brain toxicity. Our group has previously demonstrated that the oral and repeated administration (21 days) of MeHg (40 mg/L) induced MeHg brain accumulation at toxic concentrations, and a pattern of severe cortical and cerebellar biochemical and behavioral. In order to assess neurotoxicity, the neurochemical parameters, namely, mitochondrial complexes I, II, II-III and IV, glutathione peroxidase (GPx) and glutathione reductase (GR) activities, the content of thiobarbituric acid-reactive substances (TBA-RS), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and brain-derived neurotrophic factor (BDNF), as well as, metal deposition were investigated in mouse cerebral cortex. Cortical neurotoxicity induced by brain MeHg deposition was characterized by the reduction of complexes I, II, and IV activities, reduction of GPx and increased GR activities, increased TBA-RS and 8-OHdG content, and reduced BDNF levels. The daily treatment with (PhSe)2 was able to counteract the inhibitory effect of MeHg on mitochondrial activities, the increased oxidative stress parameters, TBA-RS and 8-OHdG levels, and the reduction of BDNF content. The observed protective (PhSe)2 effect could be linked to its antioxidant properties and/or its ability to reduce MeHg deposition in brain, which was here histochemically corroborated. Altogether, these data indicate that (PhSe)2 could be consider as a neuroprotectant compound to be tested under neurotoxicity.

Selenium – a fascinating antioxidant of protective properties

“…Diphenyl diselenide was proved effective against the toxicity of mercury in rodents, while selenite showed no efficacy. 1,19 It was also found that the influence of selenium was dependent on its dose. 10,36 The detailed information is collected in Tables 3-8.…”

“…21 The research more and more often includes selenoorganic compounds -either naturally occurring forms or newly synthesized substances, e.g., selenomethionine, naphthalimide-based selenocyanates, 2-(5-selenocyanatopentyl)-benzo[de]isoquinoline-1,3-dione, diphenyl diselenide, selenofuranoside, p-methoxyldiphenyl diselenide, selenocyanates, and diphenylmethyl selenocyanate. [4][5][6]9,16,17,19,20,[22][23][24][25][26] The results regarding the comparison of inorganic and organic compounds are not fully consistent, although the newest studies usually reveal plasma urea and plasma creatinine ↑; kidney vitamin C, GSH, GST, GPx, GR, CAT, δ-ALA-D ↓ p-methoxyl-diphenyl diselenide 50 mg/kg or 100 mg/kg, orally 6 days lower dose: plasma urea (±); plasma creatinine (0); kidney GSH, GST, GPx, GR, δ-ALA-D (±); kidney vitamin C, CAT (+) higher dose: plasma urea and plasma creatinine (±), kidney GSH, GST, GPx, GR, vitamin C, CAT (+) kidney δ-ALA-D (±) none ↓ -decrease; ↑ -increase; (+) -full protection; (±) -partial protection; (0) -lack of protection; GST -glutathione S-transferase; GPx -glutathione peroxidase; CAT -catalase; SOD -superoxide dismutase; GSH -reduced glutathione; TBARS -thiobarbituric acid-reactive substances; GR -glutathione reductase; δ-ALA-D -δ-aminolevulinic dehydratase..…”

“…3,8,10,[14][15][16][17][18] Organic compounds have been widely studied recently due to the similarity of the activity of some of them (e.g., ebselen or diphenyl diselenide) to that shown by glutathione peroxidase. 19 Diphenyl diselenide has also been proved to possess many beneficial pharmacological properties: anti-hyperglycemic, anti-hyperlipidemic, hepatoprotective, antiulcer, and antidepressant. 19,20 …”

“…19 Diphenyl diselenide has also been proved to possess many beneficial pharmacological properties: anti-hyperglycemic, anti-hyperlipidemic, hepatoprotective, antiulcer, and antidepressant. 19,20 …”

Selenium in the therapy of neurological diseases. Where is it going?

“…Genetic defects in this selenoprotein are associated with severe health issues. SelP−/−knockout mice display a neurological phenotype with subtle disruption of memory processes and spatial learning [60]. Moreover, other researchers have shown reduction in brain Se levels followed by a decrease in Se-dependent enzyme activity and impaired motor coordination in the same model [52,61,62].…”