An organic selenium compound attenuates apomorphine-induced stereotypy in mice

Machado, Miriana S.; Rosa, Renato Moreira; Dantas, Andrea S.; Reolon, Gustavo Kellermann; Appelt, Helmoz R.; Braga, Antônio L.; Henriques, João Antônio Pêgas; Roesler, Rafaël

doi:10.1016/j.neulet.2006.09.079

Cited by 40 publications

(16 citation statements)

References 43 publications

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“…Different from our expectation the effect of diphenyl diselenide was higher than its disubstituted analogs. 65 Motivated by a previous reported study showing that (m-CF 3 -C 6 H 4 Se) 2 , different from (PhSe) 2 , lacks proconvulsant activity when injected to mice, 21 Machado and co-workers 84 have demonstrated that (CF 3 -C 6 H 4 Se) 2 specifically attenuated behavioral features associated with a mouse model of psychosis at a dose that did not affect the behavioral parameters. In a recent study, we provide pharmacological and neurochemical points of evidence for the anxiolytic-like effect elicited by (m-CF 3 -C 6 H 4 Se) 2 in mice.…”

Section: Disubstituted Diselenidesmentioning

confidence: 97%

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: Disubstituted Diselenidesmentioning

confidence: 97%

Diphenyl diselenide a janus-faced molecule

Nogueira

Rocha

2010

J. Braz. Chem. Soc.

203

106

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“…Selenium, in line with its powerful antioxidant function, prevented all of the alterations induced by STZ, including the cognitive deficits and the oxidative damage (198). Selenium also has been shown to be neuroprotective and beneficial for memory deficits induced by lead poisoning (237) and psychosis, without affecting baseline behavior (260). The beneficial effects of selenium also were explored in fluoride toxicity (462) and ischemia models (158), where it was shown to enhance ROS scavenging and improve short-term memory impairments.…”

Section: Seleniummentioning

confidence: 99%

Reactive Oxygen Species in the Regulation of Synaptic Plasticity and Memory

Massaad

Klann

2011

Antioxidants & Redox Signaling

495

350

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The brain is a metabolically active organ exhibiting high oxygen consumption and robust production of reactive oxygen species (ROS). The large amounts of ROS are kept in check by an elaborate network of antioxidants, which sometimes fail and lead to neuronal oxidative stress. Thus, ROS are typically categorized as neurotoxic molecules and typically exert their detrimental effects via oxidation of essential macromolecules such as enzymes and cytoskeletal proteins. Most importantly, excessive ROS are associated with decreased performance in cognitive function. However, at physiological concentrations, ROS are involved in functional changes necessary for synaptic plasticity and hence, for normal cognitive function. The fine line of role reversal of ROS from good molecules to bad molecules is far from being fully understood. This review focuses on identifying the multiple sources of ROS in the mammalian nervous system and on presenting evidence for the critical and essential role of ROS in synaptic plasticity and memory. The review also shows that the inability to restrain either age-or pathology-related increases in ROS levels leads to opposite, detrimental effects that are involved in impairments in synaptic plasticity and memory function.

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“…DFDD has been shown to attenuate apomorphineinduced stereotypy at a dose which did not affect other behavioral parameters, clearly indicating an antipsychotic potential (60). In addition, this derivative is less toxic than DPDS and does not induce seizures in mice (30).…”

Section: Neuroprotectionmentioning

confidence: 99%

Pharmacology and toxicology of diphenyl diselenide in several biological models

Rosa

Roesler

Braga

et al. 2007

Braz J Med Biol Res

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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.

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An organic selenium compound attenuates apomorphine-induced stereotypy in mice

Cited by 40 publications

References 43 publications

Diphenyl diselenide a janus-faced molecule

Diphenyl diselenide a janus-faced molecule

Reactive Oxygen Species in the Regulation of Synaptic Plasticity and Memory

Pharmacology and toxicology of diphenyl diselenide in several biological models

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