Pharmacology and toxicology of diphenyl diselenide in several biological models

Abstract

The pharmacology of synthetic organoselenium compounds indicates that they can be used as antioxidants, enzyme inhibitors, neuroprotectors, anti-tumor and anti-infectious agents, and immunomodulators. In this review, we focus on the effects of diphenyl diselenide (DPDS) in various biological model organisms. DPDS possesses antioxidant activity, confirmed in several in vitro and in vivo systems, and thus has a protective effect against hepatic, renal and gastric injuries, in addition to its neuroprotective activity. The activity of the compound on the central nervous system has been studied since DPDS has lipophilic characteristics, increasing adenylyl cyclase activity and inhibiting glutamate and MK-801 binding to rat synaptic membranes. Systemic administration facilitates the formation of long-term object recognition memory in mice and has a protective effect against brain ischemia and on reserpine-induced orofacial dyskinesia in rats. On the other hand, DPDS may be toxic, mainly because of its interaction with thiol groups. In the yeast Saccharomyces cerevisiae, the molecule acts as a pro-oxidant by depleting free glutathione. Administration to mice during cadmium intoxication has the opposite effect, reducing oxidative stress in various tissues. DPDS is a potent inhibitor of δ-aminolevulinate dehydratase and chronic exposure to high doses of this compound has central effects on mouse brain, as well as liver and renal toxicity. Genotoxicity of this compound has been assessed in bacteria, haploid and diploid yeast and in a tumor cell line.

Reduction of Diphenyl Diselenide and Analogs by Mammalian Thioredoxin Reductase Is Independent of Their Gluthathione Peroxidase-Like Activity: A Possible Novel Pathway for Their Antioxidant Activity

“…Alternatively, in the absence of an excess of a low molecular weight reducing thiol, TrxR can reduce ebselen and/or ebselen diselenide using reducing equivalents from NADPH [10,11]. Diphenyl diselenide and analogs share several antioxidant and neuroprotective properties with ebselen [5,[19][20][21][22][23][24][25][26] and they are also mimetics of native GPx enzyme [5,8]. However, there is a dearth of information in the literature indicating that simple diorganyl diselenides such as diphenyl diselenide and its analogs can be substrates for TrxR.…”

Diphenyl diselenide (PhSe)2 inhibits biofilm formation by Candida albicans, increasing both ROS production and membrane permeability

“…In the last few decades, the interest in developing synthetic organic selenium compounds has increased considerably, because some of these compounds present chemical and biological antioxidant properties [21][22][23][24][25][26]. The antioxidant and neuroprotective properties of diphenyl diselenide (PhSe) 2 , a structurally simple organoselenium compound, against ischaemia and MeHg-induced toxicity have been described [27][28][29][30][31][32].…”

Free radical scavenging in vitro and biological activity of diphenyl diselenide-loaded nanocapsules: DPDS-NCS antioxidant and toxicological effects

“…7 In contrast, studies have shown that DPDS has pro-oxidative effects in vivo, such as oxidation of sulfhydryl (-SH) groups in proteins, reduction of glutathione levels (GSH), and inhibition of δ-aminolevulinic acid dehydratase (δ-ALA-D). 8 In addition, the lethal dose (LD 50 ) for a single intraperitoneal (ip) administration of DPDS in mice is 210 µmol/kg. In this regard, nanotechnology is widely applied to produce significant advantages over prodrugs, including improving the bioavailability of lipophilic molecules and increasing the safe dose of toxic compounds.…”