Toxicological evaluation of chronic exposure to the organochalcogen 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one in male rats

Mello, Amanda; Medeiros, Maria Carla; Lacerda, Denise dos Santos; Andrade, Rodrigo; Gemelli, Tanise; Guerra, Ricardo; Wannmacher, Clóvis Milton Duval; Gomez, Rosane; Funchal, Cláudia

doi:10.1016/j.fct.2012.04.042

Cited by 5 publications

(7 citation statements)

References 56 publications

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“…Evaluation of the effect of organochalcogens and other occupational and environmental toxic agents on behaviours of rodents is still scarce. The present findings are in accordance with the results of Mello et al, 11 which observed that a chronic treatment with the same organoselenium increased the total, central and peripheral ambulation as well as the rearing behaviour in the open field test in rats.…”

Section: Discussionsupporting

confidence: 94%

“…Considering that Se compounds may oxidize thiol groups and CK is a thiol containing enzyme crucial for energy homeostasis in brain tissue, it is feasible that the organoselenium may inhibit CK activity. This is in line with a previous study from our group showing that a chronic treatment with the same organoselenium inhibited CK activity in different structures in the brain of rats …”

Section: Discussionsupporting

confidence: 93%

“…The paradoxical effect of these compounds depends on the variety of chemical structure, doses, route and regimen of administration and animal species involved in the studies . Therefore, this could explain the different effects obtained here with the acute treatment and the data previously published with the chronic treatment …”

Section: Discussionmentioning

confidence: 75%

“…This is in line with a previous study from our group showing that a chronic treatment with the same organoselenium inhibited CK activity in different structures in the brain of rats. 11 Creatine kinase isoenzymes are specifically located at places of high energy demand and production, linking energy production and energy utilization by a creatine/ phosphocreatine circuit. [48][49][50] They are compartmentalized at subcellular space and coupled to sites of energy production or energy consumption.…”

Section: Discussionmentioning

confidence: 99%

“…[5][6][7][8] In this context, the organoselenium 3-methyl-1-phenyl-2-(phenylseleno) oct-2-en-1-one is an α,β-unsaturated ketone functionalized vinyl chalcogenide that can be used as potential tool in organic synthesis. [9][10][11] Organochalcogens also can cause a variety of toxic effects in the central nervous system, including behavioural changes and cognitive impairment. 12 However, some beneficial effects of organoselenium compounds on cognitive function have been also reported in rats.…”

Section: Introductionmentioning

confidence: 99%

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Acute exposure to the vinyl chalcogenide 3‐methyl‐1‐phenyl‐2‐(phenylseleno)oct‐2‐en‐1‐one induces oxidative stress in different brain area of rats

Andrade

Gemelli

Guerra

et al. 2014

Cell Biochemistry & Function

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The mechanisms that lead to the onset of organoselenium intoxication are still poorly understood. Therefore, in the present study, we investigated the effect of acute administration of 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one on some parameters of oxidative stress and on the activity of creatine kinase (CK) in different brain areas and on the behaviour in the open field test of 90-day-old male rats. Animals (n = 10/group) were treated intraperitoneally with a single dose of the organoselenium (125, 250 or 500 µg kg(-1) ), and after 1 h of the drug administration, they were exposed to the open field test, and behaviour parameters were recorded. Immediately after they were euthanized, cerebral cortex, hippocampus and cerebellum were dissected for measurement of thiobarbituric acid reactive substances (TBARS), carbonyl, sulfhydryl, catalase (CAT), superoxide dismutase (SOD) and CK activity. Our results showed that the dose of 500 µg kg(-1) of the organoselenium increased the locomotion and rearing behaviours in the open field test. Moreover, the organochalcogen enhanced TBARS in the cerebral cortex and cerebellum and increased the oxidation of proteins (carbonyl) only in the cerebral cortex. Sulfhydryl content was reduced in all brain areas, CAT activity enhanced in the hippocampus and reduced in the cerebellum and SOD activity increased in all brain structures. The organoselenium also inhibited CK activity in the cerebral cortex. Therefore, changes in motor behaviour, redox state and energy homeostasis in rats treated acutely with organoselenium support the hypotheses that the brain is a potential target for the organochalcogen action. Ltd.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Acute exposure to the vinyl chalcogenide 3‐methyl‐1‐phenyl‐2‐(phenylseleno)oct‐2‐en‐1‐one induces oxidative stress in different brain area of rats

Andrade

Gemelli

Guerra

et al. 2014

Cell Biochemistry & Function

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Toxicology and pharmacology of synthetic organoselenium compounds: an update

2021

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Here, we addressed the pharmacology and toxicology of synthetic organoselenium compounds and some naturally occurring organoselenium amino acids. The use of selenium as a tool in organic synthesis and as a pharmacological agent goes back to the middle of the nineteenth and the beginning of the twentieth centuries. The rediscovery of ebselen and its investigation in clinical trials have motivated the search for new organoselenium molecules with pharmacological properties. Although ebselen and diselenides have some overlapping pharmacological properties, their molecular targets are not identical. However, they have similar anti-inflammatory and antioxidant activities, possibly, via activation of transcription factors, regulating the expression of antioxidant genes. In short, our knowledge about the pharmacological properties of simple organoselenium compounds is still elusive. However, contrary to our early expectations that they could imitate selenoproteins, organoselenium compounds seem to have non-specific modulatory activation of antioxidant pathways and specific inhibitory effects in some thiol-containing proteins. The thiol-oxidizing properties of organoselenium compounds are considered the molecular basis of their chronic toxicity; however, the acute use of organoselenium compounds as inhibitors of specific thiol-containing enzymes can be of therapeutic significance. In summary, the outcomes of the clinical trials of ebselen as a mimetic of lithium or as an inhibitor of SARS-CoV-2 proteases will be important to the field of organoselenium synthesis. The development of computational techniques that could predict rational modifications in the structure of organoselenium compounds to increase their specificity is required to construct a library of thiol-modifying agents with selectivity toward specific target proteins.

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Subchronic treatment with acai frozen pulp prevents the brain oxidative damage in rats with acute liver failure

et al. 2016

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Acai has been used by the population due to its high nutritional value and its benefits to health, such as its antioxidant properties. The aim of this study was to evaluate the protective effect of acai frozen pulp on oxidative stress parameters in cerebral cortex, hippocampus and cerebellum of Wistar rats treated with carbon tetrachloride (CCl). Thirty male Wistar rats (90-day-old) were orally treated with water or acai frozen pulp for 14 days (7 μL/g). On the 15th day, half of the animals received treatment with mineral oil and the other half with CCl (3.0 mL/kg). The cerebral cortex, hippocampus and cerebellum were dissected and used for analysis of creatine kinase activity (CK), thiobarbituric acid reactive substances (TBARS), carbonyl, sulfhydryl, and the activity of antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD). Statistical analysis was performed by ANOVA followed by Tukey's post-test. CCl was able to inhibit CK activity in all tissues tested and to provoke lipid damage in cerebral cortex and cerebellum, and protein damage in the three tissues tested. CCl enhanced CAT activity in the cerebral cortex, and inhibited CAT activity in the hippocampus and cerebellum and reduced SOD activity in all tissues studied. Acai frozen pulp prevented the inhibition of CK, TBARS, carbonyl and CAT activity in all brain structures and only in hippocampus for SOD activity. Therefore, acai frozen pulp has antioxidant properties and maybe could be useful in the treatment of some diseases that affect the central nervous system that are associated with oxidative damage.

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Toxicological evaluation of chronic exposure to the organochalcogen 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one in male rats

Cited by 5 publications

References 56 publications

Acute exposure to the vinyl chalcogenide 3‐methyl‐1‐phenyl‐2‐(phenylseleno)oct‐2‐en‐1‐one induces oxidative stress in different brain area of rats

Acute exposure to the vinyl chalcogenide 3‐methyl‐1‐phenyl‐2‐(phenylseleno)oct‐2‐en‐1‐one induces oxidative stress in different brain area of rats

Toxicology and pharmacology of synthetic organoselenium compounds: an update

Subchronic treatment with acai frozen pulp prevents the brain oxidative damage in rats with acute liver failure

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