Mitochondrial thioredoxin reductase inhibition, selenium status, and Nrf-2 activation are determinant factors modulating the toxicity of mercury compounds

Branco, Vasco; Godinho‐Santos, Ana; Gonçalves, João; Lu, Jun; Holmgren, Arne; Carvalho, Cristina

doi:10.1016/j.freeradbiomed.2014.04.030

Cited by 89 publications

(77 citation statements)

References 67 publications

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“…Upon entering the cell, selenite (Se IV) is reduced to selenide (Se 2-) which has a very high affinity to bind mercury, and will be integrated into selenoproteins. On the other hand, selenite can lead to increased translocation of Nrf-2 to nucleus promoting TrxR1 synthesis (Branco et al, 2014). However, co-exposure to EtHg and selenite did not increase TrxR1's activity similarly to what was previously shown in HepG2 cells with MeHg (Branco et al 2014).…”

Section: Accepted Manuscriptmentioning

confidence: 71%

“…On the other hand, selenite can lead to increased translocation of Nrf-2 to nucleus promoting TrxR1 synthesis (Branco et al, 2014). However, co-exposure to EtHg and selenite did not increase TrxR1's activity similarly to what was previously shown in HepG2 cells with MeHg (Branco et al 2014). This can be attributed to a slower response of the Nrfplausible that Se 2-is unable to remove EtHg from TrxR's active site as seen for MeHg and further suggests an overlapping between the molecular mechanisms of these two organomercurial compounds.On the other hand, co-exposure of neuroblastoma and hepatoma cells to sodium selenite decreased G6PDH inhibition by all mercurials tested and fully prevented TM effects.…”

Section: Accepted Manuscriptmentioning

confidence: 71%

“…As recently demonstrated (Branco et al 2014), the protective effect of selenite on Hg 2+ toxicity is also due to the up-regulation of TrxR1 expression via the Nrf-2 pathway.…”

Section: Introductionmentioning

confidence: 66%

See 2 more Smart Citations

Toxicological effects of thiomersal and ethylmercury: Inhibition of the thioredoxin system and NADP+-dependent dehydrogenases of the pentose phosphate pathway

Rodrígues

Branco

et al. 2015

Toxicology and Applied Pharmacology

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Section: Accepted Manuscriptmentioning

confidence: 71%

Section: Accepted Manuscriptmentioning

confidence: 71%

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Toxicological effects of thiomersal and ethylmercury: Inhibition of the thioredoxin system and NADP+-dependent dehydrogenases of the pentose phosphate pathway

Rodrígues

Branco

et al. 2015

Toxicology and Applied Pharmacology

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“…The highest mean molar ratio found, Se:Hg in liver, suggests that this organ acts on Hg by demethylation and/or sequestration by Se present in selenoproteins (Kehring et al 2009). However, excessive free Se would be prooxidant and generate reactive oxygen species (Branco et al 2014). Significant (p [ 0.05) correlations were not found between size (total length) or weight with Se:Hg molar ratios.…”

Section: Discussionmentioning

confidence: 99%

“…Like Hg, Se can biomagnify through food webs (Luoma and Rainbow 2008). Other studies have shown that Se and Hg behave antagonistically so their co-occurrence reduce their toxic effects, but the outcome depends strongly on their chemical forms as well as on the molar ratio of these two elements (Parizek and Ostadalova 1967;Wang et al 2001;Ralston et al 2007;Berry and Ralston 2008;Branco et al 2012Branco et al , 2014. Interactions between Hg and Se are essential factors in evaluating risks associated with dietary exposure to Hg, because it appears that Se has a protective effect against Hg toxicity.…”

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confidence: 99%

Mercury and Selenium in Muscle and Target Organs of Scalloped Hammerhead Sharks Sphyrna lewini of the SE Gulf of California: Dietary Intake, Molar Ratios, Loads, and Human Health Risks

Bergés-Tiznado

Márquez-Farías

Lara‐Mendoza

et al. 2015

Arch Environ Contam Toxicol

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Selenium and mercury were evaluated in muscle, liver, kidney, brain, and the stomach contents of juvenile scalloped hammerhead shark Sphyrna lewini. Se:Hg molar ratios were calculated. The average Hg levels in muscle ranged from 0.12 to 1.17 μg/g (wet weight); Hg was <0.39 μg/g in liver and kidneys and <0.19 μg/g in brain. The lowest value of Se was found in muscle (0.4 μg/g) and the highest in kidney (26.7 μg/g). An excess of Se over Hg was found, with Se:Hg molar ratios >1. Correlations were found for Hg in muscle with size, age, and weight, and also for Hg in liver with size, age, and weight. Hg in muscle was significantly positive correlated to Hg in brain as well as Hg in liver was correlated to Hg in kidney. The highest Hg in preys was for carangid fishes; scombrid and carangid fishes contributed with the highest Se levels. Results suggest that more than 98 % of the total Hg and 62 % of Se end up in muscle and might be affected by factors, such as geographical area, age, size, and feeding habits. The muscle of S. lewini should be consumed by people cautiously so as not to exceed the recommended intake per week.

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Investigation of the effects of thiazole compounds on thioredoxin reductase 1 (TrxR1), glutathione S‐transferase (GST), and glutathione reductase (GR) targeted human brain glioblastoma cancer (U‐87 MG)

Korkmaz

2024

Biotech and App Biochem

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Cancer is a fatal disease that kills thousands of people worldwide. Despite the information produced by research on cancer treatment, applications in cancer treatment are limited. Therefore, scientists’ efforts to develop more effective treatment approaches continue. In the study, we aimed to determine the anticancer potential of amino thiazole compounds on human glioblastoma (U‐87 MG) and human dermal fibroblast (HDFa) cells and their inhibition effects on enzymes that cause multidrug resistance in cancer cells. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide cell viability test was performed to understand the cytotoxic properties of thiazole derivatives. The cellular death mechanisms behind thiazole application were investigated using flow cytometry analysis. According to cell viability analysis, thiazole derivatives exhibited a greater effect on U‐87 MG than the HDFa cell line in terms of cytotoxicity. Flow cytometry showed higher apoptotic cell death in U‐87 MG cells than in the HDFa cell line. It can be concluded that thiazole compounds exert anticancer effects on U‐87 MG and HDFa as well as show apoptotic properties. Their effects on thioredoxin reductase 1 (TrxR1), glutathione S‐transferase (GST), and glutathione reductase (GR) activities, which are important in the development of chemotherapeutic methods, were also examined. From the results obtained, it was determined that the 2‐amino‐4‐(p‐tolyl)thiazole (T7) compound significantly suppressed both TrxR1 and GST activities, and the 2‐amino‐6‐methylbenzothiazole (T8) compound significantly suppressed both TrxR1 and GST activities. Compound T7 was determined to be a selective inhibitor for TrxR1 and GST targeting, and compound T8 was determined to be a selective inhibitor for TrxR1 and GR targeting glioblastoma treatment.

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Mitochondrial thioredoxin reductase inhibition, selenium status, and Nrf-2 activation are determinant factors modulating the toxicity of mercury compounds

Cited by 89 publications

References 67 publications

Toxicological effects of thiomersal and ethylmercury: Inhibition of the thioredoxin system and NADP+-dependent dehydrogenases of the pentose phosphate pathway

Toxicological effects of thiomersal and ethylmercury: Inhibition of the thioredoxin system and NADP+-dependent dehydrogenases of the pentose phosphate pathway

Mercury and Selenium in Muscle and Target Organs of Scalloped Hammerhead Sharks Sphyrna lewini of the SE Gulf of California: Dietary Intake, Molar Ratios, Loads, and Human Health Risks

Investigation of the effects of thiazole compounds on thioredoxin reductase 1 (TrxR1), glutathione S‐transferase (GST), and glutathione reductase (GR) targeted human brain glioblastoma cancer (U‐87 MG)

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