On the mechanisms involved in antinociception induced by diphenyl diselenide

Zasso, Fabricio Batistella; Goncales, Carlos E.P.; Jung, Eduardo A.C.; Araldi, Dionéia; Zeni, Gilson; Rocha, João Batista Teixeira da; Nogueira, Cristina W.

doi:10.1016/j.etap.2004.08.003

Cited by 47 publications

(31 citation statements)

References 47 publications

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“…Diphenyl diselenide and ebselen produced a significant antinociceptive local effect on the late phase of the formalin test. 67 The results obtained by Zasso 67 with formalin are in better agreement with those in which local administration of diphenyl diselenide produced antinociceptive and antioedematogenic effects when co-injected with glutamate in mice. 24 The involvement of redox regulatory site of glutamate receptors in antinociceptive action of diphenyl diselenide was demonstrated.…”

Section: General Pharmacologysupporting

confidence: 75%

Diphenyl diselenide a janus-faced molecule

Nogueira

Rocha

2010

J. Braz. Chem. Soc.

203

106

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Este artigo de revisão aborda uma reflexão sobre o potencial terapêutico ou tóxico de compostos orgânicos de selênio, dando particular ênfase ao disseleneto de difenila e alguns dos seus análogos estruturais. Algumas características moleculares relacionadas com a toxicidade e farmacologia do disseleneto de difenila in vitro e in vivo são abordadas. Os artigos revisados, que abordam experimentos in vivo, indicam que a interação do disseleneto de difenila com tióis pode determinar seu potencial farmacológico ou toxicológico. Além disso, uma limitada ativação da rota de toxicidade, isto é, a oxidação controlada de moléculas de alto peso molecular, que contém grupos tióis, poderia contribuir para os efeitos farmacológicos do disseleneto de difenila. Concluise que a síntese de compostos orgânicos de selênio deve ser direcionada para o desenvolvimento de novos disselenetos de diorganoila que possam interagir com alvos moleculares específicos.In this review, we summarized the potential role of synthetic organoseleno compounds as therapeutic or toxic agents, giving emphasis almost exclusively to diphenyl diselenide, the simplest of the diaryl diselenides, and some of its analogs. We presented the main molecular aspects related to the in vitro toxicity and pharmacology of diphenyl diselenide and also provided in vivo data indicating that the interaction of diphenyl diselenide with thiols can dictate either its toxicological or pharmacological property. The papers covered in this review indicate that a limited activation of the "toxic pathway", i.e., a controlled oxidation of specific high molecular weight thiol-containing molecules could contribute to the pharmacological effects of diphenyl diselenide. In conclusion, this review reinforces the necessity of developing new diorganoyl diselenides that could interact with specific molecular targets.

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Section: General Pharmacologysupporting

confidence: 75%

Diphenyl diselenide a janus-faced molecule

Nogueira

Rocha

2010

J. Braz. Chem. Soc.

203

106

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“…Considering that pharmacological effects of (PhSe)2 including antioxidant, anti-nociceptive, anti-inflammatory, neuroprotective and hepatoprotective properties have been reported at doses of up to 10 mmol kg -1 (Bem et al, 2008(Bem et al, , 2009Borges et al, 2005;Ghisleni et al, 2003;Savegnago et al, 2006Savegnago et al, , 2007Zasso et al, 2005), this toxicological study encourages further experiments on the therapeutic properties of this compound. …”

Section: Discussionmentioning

confidence: 93%

“…In addition, Barbosa et al (2006Barbosa et al ( , 2008 showed that (PhSe)2 causes a significant reduction in the levels of blood glucose and glycated proteins in diabetic rats. The anti-nociceptive, neuroprotective, hepatoprotective and antiinflammatory properties of (PhSe)2 have been demonstrated in different in vitro and in vivo experimental models (Borges et al, 2005;Ghisleni et al, 2003;Savegnago et al, 2007;Zasso et al, 2005). Furthermore, the antioxidant ability of (PhSe)2 has been shown in several in vitro systems containing different types of *Correspondence to: A. F. de Bem,Departamento de Bioquímica,Universidade Federal de Santa Catarina,88040900,Florianópolis,SC,Universidade Federal de Santa Catarina,Florianópolis,SC,88040900,Brazil b Departamento de Biologia Celular,Embriologia e Genética,Universidade Federal de Santa Catarina,Florianópolis,SC,88040900,Brazil c tissue, including brain, liver and platelets (Borges et al, 2005;Posser et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Acute exposure of rabbits to diphenyl diselenide: a toxicological evaluation

Straliotto

Mancini

Oliveira

et al. 2010

J of Applied Toxicology

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The simple organoselenium compound diphenyl diselenide (PhSe)(2) is a promising new pharmacological agent. However, few toxicological evaluations of this molecule have been reported. We evaluated the effects of acute administration of (PhSe)(2) on toxicological parameters in rabbits. Adult New Zealand rabbits were exposed to (PhSe)(2) (5-500 micromol kg(-1) , intraperitoneally) once a day for 5 days. Exposure to 500 micromol kg(-1) caused 85% mortality. Exposure to 50 micromol kg(-1) of (PhSe)(2) increased the glutathione levels in the hippocampus, kidney, heart, muscle and blood, whereas lipoperoxidation (TBARS) decreased in the cerebellum and kidney after exposure to 5 micromol kg(-1) . The activity of glutathione peroxidase increased in the heart and muscle of rabbits treated with 50 micromol kg(-1) of (PhSe)(2) and glutathione reductase activity was reduced in the cerebellum, cerebral cortex and kidney. Treatment with (PhSe)(2) reduced the activity of δ-aminolevulinate dehydratase in the hippocampus and increased this activity in the heart, but did not alter the activity of complexes I and II of the respiratory chain in the liver and brain. Hepatic and renal biochemical and histological parameters were not modified by (PhSe)(2) and apoptosis was not detected in these tissues; however, the hepatic cells tended to accumulate fat vacuoles. These results indicated that acute toxicology to (PhSe)(2) in rabbit is dependent on the dose, which should motivate further experiments on the therapeutic properties of this compound.

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“…At anti-inflammatory and antinociceptive doses, this compound has no overt toxicity in mice, rats, or rabbits (Zasso et al 2005;de Bem et al 2006). Furthermore, DPDS has a protective role in a variety of experimental models associated with the overproduction of free radicals (Rossato et al 2002b;Borges et al 2005;Barbosa et al 2006;Ineu et al 2008).…”

Section: Introductionmentioning

confidence: 96%

Antioxidant activity and low toxicity of (E)-1-(1-(methylthio)-1-(selenopheny) hept-1-en-2-yl) pyrrolidin-2-one

et al. 2012

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The aim of the present study was to evaluate the potential pharmacological and toxicological properties of (E)-1-(1-(methylthio)-1-(selenopheny) hept-1-en-2-yl) pyrrolidin-2-one (compound 1), an organoselenium compound. In vitro experiments showed that compound 1 presented a reduction in the lipid peroxidation induced by Fe²⁺ in thiobarbituric acid-reactive species (TBARS) production, and in the generation of reactive species caused by Fe²⁺/malonate in DCFH-DA oxidation. The high dose (500 mg/kg) induced an increase on ALT but not on AST activity. Hepatic, but not cerebral, δ-ALA-D activity from mice treated with 500 mg/kg presented a significant inhibition. Brain catalase activity was significantly inhibited by 100 mg/kg whereas hepatic catalase activity showed a significant increase at all doses. Hepatic lipid peroxidation was diminished only at lowest dose (100 mg/kg) whereas for brain tissue, all doses induced a significant reduction in TBARS levels. Brain and liver ascorbic acid contents were increased only at highest dose of compound 1. Urea and creatinine levels were not significantly altered by treatments. This is a promising compound with antioxidant activity and low toxicity, suggesting the potential beneficial activity of compound 1 against oxidative damage in many parameters studied in rats and mice.

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On the mechanisms involved in antinociception induced by diphenyl diselenide

Cited by 47 publications

References 47 publications

Diphenyl diselenide a janus-faced molecule

Diphenyl diselenide a janus-faced molecule

Acute exposure of rabbits to diphenyl diselenide: a toxicological evaluation

Antioxidant activity and low toxicity of (E)-1-(1-(methylthio)-1-(selenopheny) hept-1-en-2-yl) pyrrolidin-2-one

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