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Background: The new coronavirus (SARS-CoV-2) pandemic emerged in 2019 causing millions of deaths. Vaccines were quickly developed and made available in 2021. Despite the availability of vaccines, some subjects refuse to take the immunizing or present comorbities, therefore developing serious cases of COVID-19, which makes necessary the development of antiviral drugs. Previous studies have demonstrated that ebselen, a selenium-containing molecule, can inhibit SARS-CoV-2 Mpro. In addition, selenium is a trace element that has antiviral and anti-inflammatory properties. Zidovudine (AZT) has been widely used against HIV infections and its action against SARS-CoV-2 may be altered by the structural modification with organochalcogen moieties, but this hypothesis still needs to be tested., Methods: In the present work we evaluated the Mpro inhibition capacity (in silico), the safety and antioxidant effect of six organochalcogen AZT-derivatives using the free-living nematode Caenorhabditis elegans, through acute (30 min) and chronic (48) exposure protocols., Results: We observed that the molecules were safe at a concentration range of 1-500 µM and did not alter any toxicological endpoint evaluated. Furthermore, the molecules are capable to decrease the ROS formation stimulated by hydrogen peroxide, to modulate the expression of important antioxidant enzymes such superoxide-dismutase-3 and glutathione S-transferese-4 and to stimulate the translocation of the DAF-16 to the cell nucleus. In addition, the molecules did not deplete thiol groups, which reinforces their safety and contribution to oxidative stress resistance., Conclusions: We have found that compounds S116l (a Tellurium AZT-derivative) and S116h (a Selenium-AZT derivative) presented more promising effects both in silico and in vivo, being strong candidates for further in vivo studies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Based on the Scopus record, Nitric Oxide journal (NOJ) has completed 25 years of publications. On March 8, 2022, the publication data was retrieved from the Scopus database and analyzed on VOSviewer and R-Studio (Bibliometrix R package/Biblioshiny). NOJ has published 1928 research documents majorly comprising of articles (1611/83.56%) and reviews (210/10.89%). The total citations and h-index were 56291 & 97, respectively. The per year (from 1997 to 2022) publications and citations are presented in this study. We tried to highlight some of the influential researchers, institutes, and countries. In all publications, 7450 authors have contributed with a collaboration index of 0.241. For all authors, we provided descriptive details about their total number of publications (NoP), total citations (TC), h-index, g-index, m-index, citations per paper (CPP), citation per year (CPY), HG Sqrt and Q2Index. Based on each indicator, we highlighted the top five scientists. The research publications (over time) of the top ten authors are also described. Furthermore, the collaboration network of authors is graphically presented. We also provided descriptive details about the most productive institutes. The highest number of documents are published by the University of Sao Paolo (n = 78), Brazil, while in-country sections, USA has the highest number of publications (n = 553) with 21739 citations and 69 h-index. In the same vein, for each era (five years) details about the top five countries are provided. In all publications (n = 1794), 34 European, 3 North American, 13 Asian, 10 South American, 5 Middle East, 8 African and 2 Asia Pacific countries have contributed. Numerical details about the collaboration links of all countries and the per-era contributions of the top ten countries are also provided. Based on the co-words analysis the per era research focus is graphically presented. Descriptive details about the major trends in publication in each era are also provided. We also manually analyzed 160 words that appeared more than thirty thousand (n = 30,000) times and tried to provide a broader overview of research publications. Based on Scopus record, the NOJ ranking is yearly improving and presently (2021-2022) it holds 14th and 17th positions in clinical biochemistry and physiology. The success could be attributed to all researchers, institutes, editors-in-chief, reviewers, editorial board & entire management., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Uranium (U) mining is an aquatic environmental concern because most of these harmful compounds are discharged into freshwater, reaching the saline environment as the final destination of this contaminated water. Carbonates are present in ocean waters and are essential for benthic organisms, however they may influence the U-induced toxicity. Thus, the aim of this study was to compare the toxicity of uranium nitrate (UN) and uranium acetate (UA) in Artemia salina (AS), which is one of the leading representatives of the marine biota. The cultures of AS (instar II) maintained in artificial seawater containing CaCO 3 were exposed for 24 h to different concentrations of U compounds. The results showed that AS were more sensitive to UN (LC 50  ≈ 15 μM) when compared with UA (LC 50  ≈ 245 μM) indicating higher toxicity of this U compound. Calculated U speciation indicated that Ca 2 UO 2 (CO 3 ) 3 and (UO 2 )2CO 3 (OH) 3 - complexes predominated under our experimental conditions. The immobilization/lethality was observed after 9 h of exposure for both U compounds. However, only UN caused a significant decrease (≈40%) in the acetylcholinesterase (AChE) activity when compared with control. In order to observe preliminary toxicity effects, we evaluated oxidative stress parameters, such as catalase (CAT) activity, TBARS formation, radical species (RS) generation and cell membrane injury and/or apoptosis (CMI). In this study, we demonstrate that U compounds caused a significant decrease in CAT activity. Similarly, we also observed that UN increased TBARS levels in AS at concentrations 5 times lower than AU (10 μM and 50 μM, respectively). Furthermore, RS generation and CMI were enhanced only on AS treated with UN. Overall, the effects observed here were remarkably significant in AS exposed to UN when compared with AU. In this study, we showed different profiles of toxicity for both U compounds, contributing significantly to the current and scarce understanding of the aquatic ecotoxicity of this heavy metal., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Since its inception in 1969, Chemico-Biological Interactions (CBI) has persistently published high quality research articles. As part of the journal's golden anniversary (50 years), we performed an electronic search on Scopus to get all publications details. Based on citescore, ranking & percentile, CBI holds 21st position in the top 113 relevant journals (in 2018). CBI also completed publications of 8005 manuscripts in March 2020. The highest documents were articles (6972/87.09%) followed by conference papers (588/7.34%) and reviews (252/3.14%). The maximum number of publications (385) was recorded in 2019, followed by 366 (in 2010) and 336 in 2016. Furthermore, details of the top 50 countries, top 50 authors and top 20 institutes with total publications, h-index, total citations and without selfcitations (WSC) are provided. USA (2371), China (786) and United Kingdom (658) are the top three countries, O'Brien, P.J (48), Maser, E. (45) and Lockridge, O. (35) are the top three authors and Karolinska Institutet (144), Stockholm University (102) & Ministry of Education China (94) are the top three institutes involved in research publications. More than eighty-four thousand (84,000) key words were amassed from scopus and after critical analysis we proposed a common sequence and connectivity. The top 200 articles, 200 reviews and 200 conference papers were analyzed by Vosviewer for various parameters. While, the top three (3) research articles and reviews are briefly described. The bibliometric analyses confirm a noteworthy growth of CBI in research publications and scientometric performance., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Triplaris gardneriana Wedd. (Polygonaceae family) is a plant species from Brazilian semiarid region which is used in local traditional medicine for the treatment of inflammatory conditions such as hemorrhoids., Aim of the Study: In this study, the in vitro anti-inflammatory activity of different concentrations of ethanolic extract from T. gardneriana seeds (EETg) was performed in order to contribute to the knowledge about etnomedicinal use of this plant species., Materials and Methods: The anti-inflammatory properties were evaluated through different approaches, such as in vitro protein anti-denaturation test, scavenging of reactive oxygen species (ROS) and myeloperoxidase (MPO) inhibition in human neutrophils activated by phorbol-12-myristate-13-acetate (PMA). Besides that, molecular docking was performed to provide new insights about the interaction between the major phenolic components in the plant extract and MPO., Results: EETg was characterized showing a total phenol content of 153.5 ± 6.3 μg gallic acid equivalent/mg extract, ability to remove hydrogen peroxide (H 2 O 2 ) in a concentration-dependent manner and had a spectroscopic profile which suggests the presence of hydroxyl groups. EETg was able to prevent protein denaturation ranging from 40.17 to 75.09%. The extract, at 10 and 20 μg/mL, was able to modulate neutrophils pro-inflammatory functions, such as degranulation and burst respiratory. In both assays, the EETg had anti-inflammatory effect comparable to nonsteroidal anti-inflammatory drugs. Among the main phenolic compounds of EETg, quercitrin, quercetin and catechin showed the highest binding affinity in silico to MPO., Conclusion: This study demonstrated, for the first time, that the anti-inflammatory effect of T. gardneriana seeds occurs due to its modulatory effect on human neutrophil degranulation and free-radical scavenging activity., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Methylmercury (MeHg) and Ethylmercury (EtHg) are toxic to the central nervous system. Human exposure to MeHg and EtHg results mainly from the consumption of contaminated fish and thimerosal-containing vaccines, respectively. The mechanisms underlying the toxicity of MeHg and EtHg are still elusive. Here, we compared the toxic effects of MeHg and EtHg in Saccharomyces cerevisiae (S. cerevisiae) emphasizing the involvement of oxidative stress and the identification of molecular targets from antioxidant pathways. Wild type and mutant strains with deleted genes for antioxidant defenses, namely: γ-glutamylcysteine synthetase, glutathione peroxidase, catalase, superoxide dismutase, mitochondrial peroxiredoxin, cytoplasmic thioredoxin, and redox transcription factor Yap1 were used to identify potential pathways and proteins from cell redox system targeted by MeHg and EtHg. MeHg and EtHg inhibited cell growth, decreased membrane integrity, and increased the granularity and production of reactive species (RS) in wild type yeast. The mutants were predominantly less tolerant of mercurial than wild type yeast. But, as the wild strain, mutants exhibited higher tolerance to MeHg than EtHg. Our results indicate the involvement of oxidative stress in the cytotoxicity of MeHg and EtHg and reinforce S. cerevisiae as a suitable model to explore the mechanisms of action of electrophilic toxicants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Oxidative stress and mitochondrial dysfunction are critical events in neurodegenerative diseases; therefore, molecules that increase cellular antioxidant defenses represent a future pharmacologic strategy to counteract such conditions. The aim of this study was to investigate the potential protective effect of (PhSe) 2 on mouse hippocampal cell line (HT22) exposed to tert-BuOOH (in vitro model of oxidative stress), as well as to elucidate potential mechanisms underlying this protection. Our results showed that tert-BuOOH caused time- and concentration-dependent cytotoxicity, which was preceded by increased oxidants production and mitochondrial dysfunction. (PhSe) 2 pre-incubation significantly prevented these cytotoxic events and the observed protective effects were paralleled by the upregulation of the cellular glutathione-dependent antioxidant system: (PhSe) 2 increased GSH levels (> 60%), GPx activity (6.9-fold) and the mRNA expression of antioxidant enzymes Gpx1 (3.9-fold) and Gclc (2.3-fold). Of note, the cytoprotective effect of (PhSe) 2 was significantly decreased when cells were treated with mercaptosuccinic acid, an inhibitor of GPx, indicating the involvement of GPx modulation in the observed protective effect. In summary, the present findings bring out a new action mechanism concerning the antioxidant properties of (PhSe) 2 . The observed upregulation of the glutathione-dependent antioxidant system represents a future pharmacologic possibility that goes beyond the well-known thiol-peroxidase activity of this compound., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Coffee is a drink prepared from roasted coffee beans and is lauded for its aroma and flavour. It is the third most popular beverage in the world. This beverage is known by its stimulant effect associated with the presence of methylxanthines. Caffeine, a purine-like molecule (1,3,7 trymetylxantine), is the most important bioactive compound in coffee, among others such as chlorogenic acid (CGA), diterpenes, and trigonelline. CGA is a phenolic acid with biological properties as antioxidant, anti-inflammatory, neuroprotector, hypolipidemic, and hypoglicemic. Purinergic system plays a key role inneuromodulation and homeostasis. Extracellular ATP, other nucleotides and adenosine are signalling molecules that act through their specific receptors, namely purinoceptors, P1 for nucleosides and P2 for nucleotides. They regulate many pathological processes, since adenosine, for instance, can limit the damage caused by ATP in the excitotoxicity from the neuronal cells. The primary purpose of this review is to discuss the effects of coffee, caffeine, and CGA on the purinergic system. This review focuses on the relationship/interplay between coffee, caffeine, CGA, and adenosine, and their effects on ectonucleotidases activities as well as on the modulation of P1 and P2 receptors from central nervous system and also in peripheral tissue., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Methylmercury (MeHg) is an environmental pollutant linked to many neurological defects, especially in developing individuals. The thioredoxin (TRX) system is a key redox regulator affected by MeHg toxicity, however the mechanisms and consequences of MeHg-induced dysfunction are not completely understood. This study evaluated the role of the TRX system in C. elegans susceptibility to MeHg during development. Worms lacking or overexpressing proteins from the TRX family were exposed to MeHg for 1 h at different developmental stage: L1, L4 and adult. Worms without cytoplasmic thioredoxin system exhibited age-specific susceptibility to MeHg when compared to wild-type (wt). This susceptibility corresponded partially to decreased total glutathione (GSH) levels and enhanced degeneration of dopaminergic neurons. In contrast, the overexpression of the cytoplasmic system TRX-1/TRXR-1 did not provide substantial protection against MeHg. Moreover, transgenic worms exhibited decreased protein expression for cytoplasmic thioredoxin reductase (TRXR-1). Both mitochondrial thioredoxin system TRX-2/TRXR-2, as well as other thioredoxin-like proteins: TRX-3, TRX-4, TRX-5 did not show significant role in C. elegans resistance to MeHg. Based on the current findings, the cytoplasmic thioredoxin system TRX-1/TRXR-1 emerges as an important age-sensitive protectant against MeHg toxicity in C. elegans., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Methylmercury (MeHg) is a ubiquitous and persistent environmental pollutant that induces serious neurotoxic effects. Diphenyl diselenide [(PhSe) 2 ], an organoseleno compound, exerts protective effects against MeHg toxicity, although the complete mechanism remains unclear. The aim of this study was to investigate the mechanisms involved in the protective effect of (PhSe) 2 on the toxicity induced by MeHg using wild-type Saccharomyces cerevisiae and mutants with defects in enzymes and proteins of the antioxidant defense system (yap1Δ, ybp1Δ, ctt1Δ, cat1Δ, sod1Δ, sod2Δ, gsh1Δ, gsh2Δ, gtt1Δ, gtt2Δ, gtt3Δ, gpx1Δ, gpx2Δ, trx1Δ, trx2Δ, trx3Δ, and trr2Δ). In the wild-type strain, (PhSe) 2 protected against the growth inhibition, reactive oxygen species production, and decrease in membrane integrity induced by MeHg and restored thiol levels to values indistinguishable from the control. Single deletions of yap1, sod1, sod2, gsh1, gsh2, gpx1, gpx2, trx1, trx2, and trx3 decreased the capacity of (PhSe) 2 to prevent MeHg toxicity in yeast, indicating their involvement in (PhSe) 2 protection. Together, these results suggest a role of (PhSe) 2 in modulating the gene expression of antioxidant enzymes and ABC transporters through the action of the transcription factor YAP1, preventing the oxidative damage caused by MeHg in S. cerevisiae.

Aqueous-leaf extract of Syzygium cumini and Bauhinia forficata are traditionally used in the treatment of diabetes and cancer, especially in South America, Africa, and Asia. In this study, we analyzed the effects of these extracts on oxidative and mitochondrial parameters in vitro, as well as their protective activities against toxic agents. Phytochemical screenings of the extracts were carried out by HPLC analysis. The in vitro antioxidant capacities were compared by DPPH radical scavenging and Fe(2+) chelating activities. Mitochondrial parameters observed were swelling, lipid peroxidation and dehydrogenase activity. The major chemical constituent of S. cumini was rutin. In B. forficata were predominant quercetin and gallic acid. S. cumini reduced DPPH radical more than B. forficata, and showed iron chelating activity at all tested concentrations, while B. forficata had not similar property. In mitochondria, high concentrations of B. forficata alone induced a decrease in mitochondrial dehydrogenase activity, but low concentrations of this extract prevented the effect induced by Fe(2+)+H2O2. This was also observed with high concentrations of S. cumini. Both extracts partially prevented the lipid peroxidation induced by Fe(2+)/citrate. S. cumini was effective against mitochondrial swelling induced by Ca(2+), while B. forficata alone induced swelling more than Ca(2+). This study suggests that leaf extract of S. cumini might represent a useful therapeutic for the treatment of diseases related with mitochondrial dysfunctions. On the other hand, the consumption of B. forficata should be avoided because mitochondrial damages were observed, and this possibly may pose risk to human health.

Background/aims: to examine the relationship between the antioxidant potential and severity parameters of cirrhosis in humans., Methods: fifteen patients with hepatic cirrhosis (nine subjects - Child group B, and six subjects - Child group C) and nine control subjects were enrolled in the study. The main criteria taken into account to characterize the diagnosis of cirrhosis and its complications were the AST: ALT ratio, AST to platelet ratio index, Bonacini score, Meld score and Child classification. Those parameters were determined based on laboratory results and patient's clinical records. Se, Zn, ascorbic acid (AA) levels and oxidative stress parameters were measured in blood samples of cirrhotic patients., Results: the analysis of plasma levels of Se and AA showed low concentrations in cirrhotic patients compared with control subjects (P < 0.05). Though, there was a positive correlation between plasma of Se and severity parameters of cirrhosis in patients of Child group B and C. In the activity of the antioxidant enzymes only catalase was lower in patients of Child group C compared with control group., Conclusion: we found low plasma levels of Se and AA among cirrhotic patients. However, is not clear why selenium levels tend to increase with the severity of liver cirrhosis., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)

Aqueous-methanolic extract of Parkia biglobosa bark (PBB) was screened for its polyphenolic constituents, in vitro antioxidant activity, and effect on mitochondria redox status. The in vitro antioxidant activity was assessed by using the scavenging abilities and the reducing powers of 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) diammonium salt radical cation against Fe(3+). Subsequently, the ability of PBB to inhibit lipid peroxidation induced by FeSO(4) (10 μm) and its metal-chelating potential were investigated. The effects of the extract on basal reactive oxygen species (ROS) generation and on the mitochondrial membrane potential (ΔΨm) in isolated mitochondria were determined by using 2', 7'-dichlorodihydrofluorescin (DCFH) oxidation and safranin fluorescence, respectively. PBB mitigated the Fe(II)-induced lipid peroxidation in rat tissues and showed dose-dependent scavenging of DPPH (IC(50): 98.33 ± 10.0 μg/mL) and ABTS. (trolox equivalent antioxidant concentration, TEAC value = 0.05), with considerable ferric-reducing and moderate metal-chelating abilities. PBB caused slight decreases in both the liver and the brain mitochondria potentials and resulted in a significant decrease (p < 0.001) in DCFH oxidation. Screening for polyphenolics using high-performance liquid chromatography coupled to a diode array detector (HPLC-DAD) revealed the presence of caffeic acid, gallic acid, catechin, epigalocatechin, rutin, and quercetin. These results demonstrate for the first time the considerable in vitro antioxidant activity and favorable effect of PBB on mitochondria redox status and provide justification for the use of the plant in ethnomedicine., (Copyright © 2014. Published by Elsevier B.V.)

Manganese (Mn) is an essential element for human health. However, at high concentrations Mn may be neurotoxic. Mn accumulates in astrocytes, affecting their redox status. In view of the high antioxidant and anti-inflammatory properties of the exotic Brazilian fruit açaí (Euterpe oleracea Mart.), its methanolic extract was obtained by solid-phase extraction (SPE). This açaí extract showed considerable anthocyanins content and direct antioxidant capacity. The açaí extract scavenged 2,2-diphenyl-1-picrylhydrazyl radicals (DPPH•) with an EC₅₀ of 19.1 ppm, showing higher antioxidant activity compared to butylated hydroxytoluene (BHT), but lower than ascorbic acid and quercetin. This obtained açaí extract also attenuated Mn-induced oxidative stress in primary cultured astrocytes. Specifically, the açaí extract at an optimal and nutritionally relevant concentration of 0.1 μg/ml prevented Mn-induced oxidative stress by (1) restoring GSH/GSSG ratio and net glutamate uptake, (2) protecting astrocytic membranes from lipid peroxidation, and (3) decreasing Mn-induced expression of erythroid 2-related factor (Nrf2) protein. A larger quantity of açaí extract exacerbated the effects of Mn on these parameters except with respect to lipid peroxidation assessed by means of F₂-isoprostanes. These studies indicate that at nutritionally relevant concentration, anthocyanins obtained from açaí protect astrocytes against Mn neurotoxicity, but at high concentrations, the "pro-oxidant" effects of its constituents likely prevail. Future studies may be profitably directed at potential protective effects of açaí anthocyanins in nutraceutical formulations.

Introduction: Cellular antioxidant signaling can be altered either by thyroid disturbances or by selenium status., Aims: To investigate whether or not dietary diphenyl diselenide can modify the expression of genes of antioxidant enzymes and endpoint markers of oxidative stress under hypothyroid conditions., Methods: Female rats were rendered hypothyroid by continuous exposure to methimazole (MTZ; 20 mg/100 ml in the drinking water) for 3 months. Concomitantly, MTZ-treated rats were either fed or not with a diet containing diphenyl diselenide (5 ppm). mRNA levels of antioxidant enzymes and antioxidant/oxidant status were determined in the cerebral cortex, hippocampus and striatum., Results: Hypothyroidism caused a marked upregulation in mRNA expression of catalase, superoxide dismutase (SOD-1, SOD-3), glutathione peroxidase (GPx-1, GPx-4) and thioredoxin reductase (TrxR-1) in brain structures. SOD-2 was increased in the cortex and striatum, while TrxR-2 increased in the cerebral cortex. The increase in mRNA expression of antioxidant enzymes was positively correlated with the Nrf-2 transcription in the cortex and hippocampus. Hypothyroidism caused oxidative stress, namely an increase in lipid peroxidation and reactive oxygen species levels in the hippocampus and striatum, and a decrease in nonprotein thiols in the cerebral cortex. Diphenyl diselenide was effective in reducing brain oxidative stress and normalizing most of the changes observed in gene expression of antioxidant enzymes., Conclusion: The present work corroborates and extends that hypothyroidism disrupts antioxidant enzyme gene expression and causes oxidative stress in the brain. Furthermore, diphenyl diselenide may be considered a promising molecule to counteract these effects in a hypothyroidism state., (© 2014 S. Karger AG, Basel.)

The aim of this study was to evaluate the potential positive effect of black grape juice (BGJ) on lipid peroxidation considering Total Body Irradiation (TBI) in Wistar rats. As a potential feasible means of evaluation in situ, blood serum lactate dehydrogenase (LDH) levels were evaluated as a marker for heart damage from acute radiation syndrome (ARS). Twenty rats were divided into four groups, two of them being irradiated by gamma-rays from a Co-60 source. Animals were treated by gavage with 2 mL per day of BGJ or placebo for one week before and 4 days after 6 Gy whole body gamma-irradiation, when they were euthanasiated. LDH on serum and lipid peroxidation on heart tissue were evaluated. High concentration of metabolites from lipid peroxidation in heart, and high LDH level on serum were found only in gamma-irradiated group given placebo, mainly at the first 24 h after radiation. Phytochemical analysis of BGJ was performed by determining total phenolics, flavonoids, and tannins followed by a high-performance liquid chromatography (HPLC/DAD) analysis, which showed resveratrol as the major constituent. Results suggest that BGJ is a good protective candidate compound against heart damage from ARS and its effects suggest its use as a radiomodifier.