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

Abstract

Selenium compounds, such as diphenyl diselenide (DPDS), have been shown to exhibit biological activity, including antioxidant effects. However, the use of DPDS in pharmacology is limited due to in vivo pro-oxidative effects. In addition, studies have shown that DPDS-loaded nanocapsules (DPDS-NCS) have greater bioavailability than free DPDS in mice. Accordingly, the aim of this study was to investigate the antioxidant properties of DPDS-NCS in vitro and biological activity in mice. Our in vitro results suggested that DPDS-NCS significantly reduced the production of reactive oxygen species and Fe(II)-induced lipid peroxidation (LPO) in brain. The administration of DPDS-NCS did not result in death or change the levels of endogenous reduced or oxidized glutathione after 72 hours of exposure. Moreover, ex vivo assays demonstrated that DPDS-NCS significantly decreased the LPO and reactive oxygen species levels in the brain. In addition, the highest dose of DPDS-NCS significantly reduced Fe(II)- and sodium nitroprusside-induced LPO in the brain and Fe(II)-induced LPO in the liver. Also, δ-aminolevulinate acid dehydratase within the brain was inhibited only in the highest dose of DPDS-NCS. In conclusion, our data demonstrated that DPDS-NCS exhibited low toxicity in mice and have significant antioxidant characteristics, indicating that nanoencapsulation is a safer method of DPDS administration.

Selenium Compounds as Novel Potential Anticancer Agents

“…In this study, inhibition of δ-ALA-D, an increase in aspartate (AST) and alanine aminotransferase (ALT) activities, and a decrease in urea levels were observed, with no effect on creatinine levels, showing that the compound had a hepatotoxic effect but no effect on renal function [56]. A very important finding is that in studies using diselenides-loaded nanocapsules, no toxic effects on mice were shown, which gives hope for a reduction in their harmful properties and possible application in human trials in the future [55,58]. Summarizing the toxicological data of diselenides in in vivo studies, more information from further animal studies on them is needed to unambiguously determine the exact mechanism of their harmful effects on the body, as well as methods to prevent them.…”

“…Oral administration of 30 mg/kg (supranutritional dose of diphenyl diselenide) for 8 months was non-toxic in rabbits, whereas acute intraperitoneal administration of 1.56 and 15.6 mg/kg was hepatotoxic to them, while a dose of 156 mg/kg was lethal to 85% of the population [52]. The main mechanism responsible for the toxic properties of diselenides is their prooxidant activity, which involves interaction with functionally relevant -SH (thiol) groups of proteins, leading to their oxidation and loss/decrease in their function [53,55,56]. Depletion of intracellular GSH is one of these effects [53,55].…”

“…The main mechanism responsible for the toxic properties of diselenides is their prooxidant activity, which involves interaction with functionally relevant -SH (thiol) groups of proteins, leading to their oxidation and loss/decrease in their function [53,55,56]. Depletion of intracellular GSH is one of these effects [53,55]. Furthermore, by the same mechanism, these compounds can inhibit the enzyme δ-aminolevulinic acid dehydratase (δ-ALA-D) in the blood, kidney, liver, and brain (highly lipophilic molecules that can cross the blood-brain barrier (BBB)) [52,53,55,56].…”

“…Depletion of intracellular GSH is one of these effects [53,55]. Furthermore, by the same mechanism, these compounds can inhibit the enzyme δ-aminolevulinic acid dehydratase (δ-ALA-D) in the blood, kidney, liver, and brain (highly lipophilic molecules that can cross the blood-brain barrier (BBB)) [52,53,55,56]. Inhibition of this enzyme in the blood results in the accumulation of aminolevulinic acid (ALA), characterized by some prooxidant properties [53].…”