Organochalcogens Inhibit Mitochondrial Complexes I and II in Rat Brain: Possible Implications for Neurotoxicity

Puntel, Robson Luiz; Roos, Daniel Henrique; Seeger, Rodrigo Lopes; Aschner, Michael; Rocha, João Batista Teixeira da

doi:10.1007/s12640-012-9365-0

Cited by 7 publications

(7 citation statements)

References 80 publications

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“…In an extension of this study, using renal and hepatic mitochondria, ebselen and diphenyl diselenide inhibited the activity of complex I and II, without changing the complex III and IV. These effects were reversed by GSH and then related to the oxidation of critical thiol groups from mitochondrial complexes I and II (Puntel et al 2013 ).…”

Section: Toxicity Of Organoselenium Compoundsmentioning

confidence: 99%

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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Section: Toxicity Of Organoselenium Compoundsmentioning

confidence: 99%

Toxicology and pharmacology of synthetic organoselenium compounds: an update

2021

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“…In this context, other studies showed that E. coli exposed to tellurium compounds exhibited a decrease in ATP levels, an increase in ROS generation, carbonylation of proteins, and a decrease in cellular reduced-thiol content [14,15,17,38,39]. The oxidation of thiols is associated with cell toxicity and death [17,23,24].…”

Section: Discussionmentioning

confidence: 98%

“…A telluroacetylene compound, 2-phenylethynylbutyltellurium (PEBT), at a low concentration has shown pharmacological effects in animal models of neurotoxicity and memory [20][21][22]. In contrast, several studies have established the toxicity of organotellurium compounds, including PEBT, which is associated with the oxidation of thiol groups in bioactive molecules, inhibiting sulfhydryl enzymes (δ-aminolevulinate dehydratase and Na + K + ATPase), or even decreasing the glutathione (GSH) concentration [20,21,[23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial effect of 2-phenylethynyl-butyltellurium in Escherichia coli and its association with oxidative stress

Pinheiro

Bortolotto

Araújo

et al. 2018

Journal of Microbiology and Biotechnology

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This study aimed to evaluate the antimicrobial activity of 2-phenylethynyl-butyltellurium (PEBT) in Escherichia coli and the relation to its pro-oxidant effect. For this, we carried out the disk diffusion test, minimum inhibitory concentration (MIC) assay, and survival curve analysis. We also measured the level of extracellular reactive oxygen species (ROS), activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and level of nonprotein thiols (NPSH). PEBT at 1.28 and 0.128 mg/disk exhibited antimicrobial capability in the disk diffusion test, with an MIC value of 1.92 mg/ml, whereas PEBT at 0.96, 1.92, and 3.84 mg/ml inhibited bacterial growth after a 9-h exposure. PEBT at 3.84, 1.92, and 0.96 mg/ml increased extracellular ROS production, decreased the intracellular NPSH level, and reduced the SOD and CAT activities. Glutathione or ascorbic acid in the medium protected the bacterial cells from the antimicrobial effect of PEBT. In conclusion, PEBT exhibited antimicrobial activity against E. coli, involving the generation of ROS, oxidation of NPSH, and reduction of the antioxidant defenses in the bacterial cells.

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“…The activity of complex I was determined spectrophotometrically at 30 ºC using mitochondria prepared as above and suspended in 100 mM phosphate buffer (pH 7.4) as previously described (Navarro et al 2002(Navarro et al , 2004. The reaction was initiated by addition D r a f t of NADH at a final concentration of 100 µM, and the enzymatic activity was determined by following the decrease in absorbance at 340 nm (Puntel et al 2013).…”

Section: Mitochondrial Complex Activity Assaymentioning

confidence: 99%

Protective effect of (−)-α-bisabolol on rotenone-induced toxicity in Drosophila melanogaster

Leite

Ecker

Seeger

et al. 2018

Can. J. Physiol. Pharmacol.

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(-)-α-Bisabolol (BISA) is a sesquiterpene alcohol, which has several recognized biological activities, including anti-inflammatory, anti-irritant, and antibacterial properties. In the present study, we investigated the influence of BISA (5, 25, and 250 μmol/L) on rotenone (500 μmol/L)-induced toxicity in Drosophila melanogaster for 7 days. BISA supplementation significantly decreased rotenone-induced mortality and locomotor deficits. The loss of motor function induced by rotenone correlated with a significant change in stress response factors; it decreased thiol levels, inhibited mitochondria complex I, and increased the mRNA expression of antioxidant marker proteins such as superoxide dismutase (SOD), catalase (CAT), and the keap1 gene product. Taken together, our findings indicate that the toxicity of rotenone is likely due to the direct inhibition of complex I activity, resulting in a high level of oxidative stress. Dietary supplementation with BISA affected the expression of SOD mRNA only at a concentration of 250 μmol/L, and did not affect any other parameter measured. Our results showed a protective effect of BISA on rotenone-induced mortality and locomotor deficits in Drosophila; this effect did not correlate with mitochondrial complex I activity, but may be related to the antioxidant protection afforded by eliminating superoxide generated as a result of rotenone-induced mitochondrial dysfunction.

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Organochalcogens Inhibit Mitochondrial Complexes I and II in Rat Brain: Possible Implications for Neurotoxicity

Cited by 7 publications

References 80 publications

Toxicology and pharmacology of synthetic organoselenium compounds: an update

Toxicology and pharmacology of synthetic organoselenium compounds: an update

Antimicrobial effect of 2-phenylethynyl-butyltellurium in Escherichia coli and its association with oxidative stress

Protective effect of (−)-α-bisabolol on rotenone-induced toxicity in Drosophila melanogaster

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