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

Sílvio Terra Stefanello,1 Fernando Dobrachinski,1 Nélson Rodrigues de Carvalho,1 Guilherme Pires Amaral,1 Rômulo Pillon Barcelos,1 Vitor Antunes Oliveira,1 Cláudia Sirlene Oliveira,1 Camila Ferrazza Alves Giordani,2 Maria Ester Pereira,1 Oscar Endrigo Dorneles Rodrigues,2 Félix Alexandre Antunes Soares1 1Departamento de Bioquímica e Biologia Molecular, 2Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, Brazil 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. Keywords: diphenyl diselenide, DPDS-NCS, lipid peroxidation, antioxidant properties, δ-ALA-

Effect of 6 weeks of swimming training on lactate threshold, time to exhaustion, and body weight.

<p>(A–C) Values are mean ±SEM (n = 14). Means without a common letter differ, p<0.05.</p

MnSOD activity, TBARS and protein carbonyls levels both after 6 weeks of swimming training and an exhaustive protocol test.

<p>(A–C) Values are mean ±SEM (n = 7). Means without a common letter differ, p<0.05. MnSOD: manganese superoxide dismutase; TBARS: thiobarbituric acid reactive substances; DNPH: dinitrophenylhydrazine.</p

GSH, GSSG, and GSH/GSSG ratio levels both after 6 weeks of swimming training and an exhaustive protocol test.

<p>(A–C) Values are mean ± SEM (n = 7). Means without a common letter differ, p<0.05. GSH: reduced glutathione; GSSG: oxidized glutathione.</p

MTT reduction and membrane potential, and ROS production both after 6 weeks of swimming training and an exhaustive protocol test.

<p>(A–C) Values are mean ±SEM (n = 7). Means without a common letter differ, p<0.05. ROS: reactive oxygen species; MTT: Methyl-tetrazolium; DCF-oxid: oxidized dichlorofluorescein diacetate; <i>Δψ</i>: membrane potential.</p

Timeline of the swimming training schedule and exhaustive protocol test data collection.

<p>Timeline of the swimming training schedule and exhaustive protocol test data collection.</p