Computational analysis of the interactions between Ebselen and derivatives with the active site of the main protease from SARS-CoV-2.

The main protease (Mpro) of the novel coronavirus SARS-CoV-2 is a key target for developing antiviral drugs. Ebselen (EbSe) is a selenium-containing compound that has been shown to inhibit Mpro in vitro by forming a covalent bond with the cysteine (Cys) residue in the active site of the enzyme. However, EbSe can also bind to other proteins, like albumin, and low molecular weight compounds that have free thiol groups, such as Cys and glutathione (GSH), which may affect its availability and activity. In this study, we analyzed the Mpro interaction with EbSe, its analogues, and its metabolites with Cys, GSH, and albumin by molecular docking. We also simulated the electronic structure of the generated molecules by density functional theory (DFT) and explored the stability of EbSe and one of its best derivatives, EbSe-2,5-MeClPh, in the catalytic pocket of Mpro through covalent docking and molecular dynamics. Our results show that EbSe and its analogues bound to GSH/albumin have larger distance between the selenium atom of the ligands and the sulfur atom of Cys145 of Mpro than the other compounds. This suggests that EbSe and its GSH/albumin-analogues may have less affinity for the active site of Mpro. EbSe-2,5-MeClPh was found one of the best molecules, and in molecular dynamics simulations, it showed to undergo more conformational changes in the active site of Mpro, in relation to EbSe, which remained stable in the catalytic pocket. Moreover, this study also reveals that all compounds have the potential to interact closely with the active site of Mpro, providing us with a concept of which derivatives may be promising for in vitro analysis in the future. We propose that these compounds are potential covalent inhibitors of Mpro and that organoselenium compounds are molecules that should be studied for their antiviral properties.

Relationship between selenium status, selenoproteins and COVID-19 and other inflammatory diseases: A critical review.

The antioxidant effects of selenium as a component of selenoproteins has been thought to modulate host immunity and viral pathogenesis. Accordingly, the association of low dietary selenium status with inflammatory and immunodeficiency has been reported in the literature; however, the causal role of selenium deficiency in chronic inflammatory diseases and viral infection is still undefined. The COVID-19, characterized by acute respiratory syndrome and caused by the novel coronavirus 2, SARS-CoV-2, has infected millions of individuals worldwide since late 2019. The severity and mortality from COVID-19 have been associated with several factor, including age, sex and selenium deficiency. However, available data on selenium status and COVID-19 are limited, and a possible causative role for selenium deficiency in COVID-19 severity has yet to be fully addressed. In this context, we review the relationship between selenium, selenoproteins, COVID-19, immune and inflammatory responses, viral infection, and aging. Regardless of the role of selenium in immune and inflammatory responses, we emphasize that selenium supplementation should be indicated after a selenium deficiency be detected, particularly, in view of the critical role played by selenoproteins in human health. In addition, the levels of selenium should be monitored after the start of supplementation and discontinued as soon as normal levels are reached. Periodic assessment of selenium levels after supplementation is a critical issue to avoid over production of toxic metabolites of selenide because under normal conditions, selenoproteins attain saturated expression levels that limits their potential deleterious metabolic effects.

(MeOPhSe)2, a synthetic organic selenium compound, inhibits virulence factors of Candida krusei: Adherence to cervical epithelial cells and biofilm formation.

BACKGROUND: Systemic candidiasis is produced by Candida albicans or non-albicans Candida species, opportunistic fungi that produce both superficial and invasive infections. Despite the availability of a wide range of antifungal agents for the treatment of candidiasis, failure of therapy is observed frequently, which opens new avenues in the field of alternative therapeutic strategies. METHODS: The effects of p,p'-methoxyl-diphenyl diselenide [(MeOPhSe)2], a synthetic organic selenium (organochalcogen) compound, were investigated on virulence factors of C. krusei and compared with its antifungal effects on the virulence factors related to adhesion to cervical epithelial cell surfaces with C. albicans. RESULTS: (MeOPhSe)2, a compound non-toxic in epithelial (HeLa) and fibroblastic (Vero) cells, inhibited the growth in a dose-dependent manner and changed the kinetics parameters of C. krusei and, most importantly, extending the duration of lag phase of growth, inhibiting biofilm formation, and changing the structure of biofilm. Also, (MeOPhSe)2 reduced C. albicans and C. krusei adherence to cervical epithelial cells, an important factor for the early stage of the Candida-host interaction. The reduction was 37.24 ± 2.7 % in C. krusei (p = 0.00153) and 32.84 ± 3.2 % in C. albicans (p = 0.0072) at 20 µM (MeOPhSe)2, and the effect is in a concentration-dependent manner. Surprisingly, the antifungal potential on adhesion was similar between both species, indicating the potential of (MeOPhSe)2 as a promising antifungal drug against different Candida infections. CONCLUSION: Overall, we demonstrated the potential of (MeOPhSe)2 as an effective antifungal drug against the virulence factors of Candida species.

Effects of Gender and Geographical Origin on the Chemical Composition and Antiradical Activity of Baccharis myriocephala and Baccharis trimera.

This study aimed to characterize and compare essential oils and ethyl acetate fractions obtained in basic and acidic conditions from both male and female Baccharis species (Baccharis myriocephala and Baccharis trimera) from two different Brazilian regions. Samples were characterized according to their chemical compositions and antiradical activity by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays. Principal component analysis (PCA) provided a clear separation regarding the chemical composition of essential oils from the samples obtained from different regions by using gas chromatography-mass spectrometry with flame-ionization detection (GC-MS-FID). PCA also revealed that gender and region of plant collections did not influence the chemical composition and antiradical activity of ethyl acetate fractions, which was corroborated with hierarchical cluster analysis (HCA) data. High performance liquid chromatography with diode-array detector (HPLC-DAD) identified significant quantities of flavonoids and phenolic acids in the fractions obtained in basic and acidic fractions, respectively. The obtained results clearly demonstrated that the geographical region of plant collection influenced the chemical composition of essential oils from the studied Baccharis species. Moreover, the obtained fractions were constituted by several antiradical compounds, which reinforced the usage of these species in folk medicine.

Dietary supplementation of jute leaf (Corchorus olitorius) modulates hepatic delta-aminolevulinic acid dehydratase (δ-ALAD) activity and oxidative status in high-fat fed/low streptozotocin-induced diabetic rats.

Impaired liver function is associated with decreased hepatic delta-aminolevulinic acid dehydratase (δ-ALAD) activity in diabetes mellitus. Hence, this study described the effect of dietary jute leaf (Corchorus olitorius) on hepatic δ-ALAD activity in high-fat fed combined with low-dose streptozotocin administered diabetic rats. Animals were fed diets containing 35% fat for 14 days prior to a single administration of low-dose (35 mg/kg body weight) streptozotocin to induce diabetes. Thereafter, the animals were randomly placed in groups and fed 100 mg/g jute leaf-supplemented diets for 30 days. The result showed that jute leaf supplementation significantly (p < 0.05) reversed the decreased hepatic δ-ALAD activity, increased hepatic catalase and SOD activity accompanying the decrease in serum AST and AST activities. This finding suggests that restoration of hepatic δ-ALAD activity, modulation of hepatic function biomarkers, and increase in antioxidant status could be possible underlying events mediating the hepatoprotective effect of jute leaf in diabetic conditions. PRACTICAL APPLICATIONS: Decrease in hepatic δ-ALAD activity has been associated with diabetes-induced hepatotoxicity arising from prolonged and uncontrolled hyperglycemia. Therefore, increased δ-ALAD activity represents improved hepatic function in diabetic situations. Antidiabetic properties of jute leaf have been demonstrated but information on its effect on hepatic δ-ALAD is lacking. Thus, this study revealed that dietary supplementation of jute leaf restored hepatic δ-ALAD activities and improved liver antioxidant status in diabetic rats which is an indication of its hepatoprotective properties.

Acute oral toxicity and antioxidant studies of an amine-based diselenide.

BACKGROUND: Organochalcogen compounds have attracted the interest of a multitude of studies for their promising Pharmacological and biological activities. The antioxidant activity and acute toxicity of an organoselenium compound, 1-(2-(2-(2-(1-aminoethyl)phenyl)diselanyl)phenyl)ethanamine (APDP) was determined in mice. METHODS: Mice were randomly divided into four groups, with each group comprising of seven animals. Canola oil (1ml/kg of body weight) was administered to 1st group, while 2nd, 3rd & 4th groups were administered with 10 mg/kg, 30 mg/kg & 350 mg/kg of APDP respectively. APDP was administered by Intragastric gavage as a single oral dose. RESULTS: The APDP oral administration was found to be safe up to 350 mg/kg of body weight and no deaths of animals were recorded. The lethal dose 50 (LD50) for APDP was determined at 72 h and was estimated to be > 350 mg/kg. After acute treatment, all mice were sacrificed by decapitation to determine the antioxidant enzymes and lipid peroxidation values for the treated mice liver. No fluctuation in lipid peroxidation, vitamin C and non protein thiol (NPSH) levels was observed due to the administration of APDP. hepatic α-ALA-D activity, catalase (CAT), superoxide dismutase (SOD) and the biochemical parameters were evaluated. Experimental observation demonstrated that APDP protected Fe(II) induced thiobarbituric acid reactive substances (TBARS) production in liver homogenate significantly (p < 0.05). The administration of APDP (an amine-based diselenide) both in vitro and in vivo clearly demonstrated that this potential compound has no acute toxicity towards mice among all the tested parameter. CONCLUSION: On the basis of experimental results, it is concluded that APDP is a potential candidate as an antioxidant compound for studying pharmacological properties.

Safety profile of AZT derivatives: Organoselenium moieties confer different cytotoxic responses in fresh human erythrocytes during in vitro exposures.

INTRODUCTION: The incorporation of selenium in the structure of nucleosides is a promising strategy to develop novel therapeutic molecules. OBJECTIVE: To assess the toxic effects of three AZT derivatives containing organoselenium moieties on human erythrocytes. METHODOLOGY: Freshly human erythrocytes were acutely treated with AZT and selenium derivatives SZ1 (chlorophenylseleno), SZ2 (phenylseleno) and SZ3 (methylphenylseleno) at concentrations ranging from 10 to 500 µM. Afterwards, parameters related to membrane damage, redox dyshomeostasis and eryptosis were determined in the cells. RESULTS: The effects of AZT and derivatives toward erythrocytes differed considerably. Overall, the SZ3 exhibited similar effect profiles to the prototypal AZT, without causing cytotoxicity. Contrary, the derivative SZ1 induced hemolysis and increased the membrane fragility of cells. Reactive species generation, lipid peroxidation and thiol depletion were also substantially increased in cells after exposure to SZ1. δ-ALA-D and Na+/K+-ATPase activities were inhibited by derivatives SZ1 and SZ2. Additionally, both derivatives caused eryptosis, promoting cell shrinkage and translocation of phosphatidylserine at the membrane surface. The size and granularity of erythrocytes were not modified by any compound. CONCLUSION: The insertion of either chlorophenylseleno or, in a certain way, phenylseleno moietes in the structure of AZT molecule was harmful to erythrocytes and this effect seems to involve a pro-oxidant activity. This was not true for the derivative encompassing methylphenylseleno portion, making it a promising candidate for pharmacological studies.

Caffeine-supplemented diet modulates oxidative stress markers and improves locomotor behavior in the lobster cockroach Nauphoeta cinerea.

The effects of caffeine supplementation is well documented in conventional animal models, however, in the lobster cockroaches Nauphoeta cinerea, they have not been reported. Thus, the aim of this study was to investigate the locomotor behavior and biochemical endpoints in the head of the nymphs of N. cinerea following 60 days exposure to food supplemented with 0, 0.5, 1.0, 2.5, 5.0 and 10.0 mg of caffeine/g of diet. The analysis of the locomotor behavior using the video-tracking software, Any-maze, for 12 min revealed that caffeine supplementation caused significant behavioral improvement. There was increase in distance travelled, velocity, frequency of rotation and turn angle (stereotypical behavior such as circling movements), and this was supported by the representative track plots of the path travelled by cockroaches in the open-field arena. In addition, caffeine supplementation markedly increased total thiol and non-protein thiol glutathione (GSH) levels in the heads of cockroaches, and this was in parallel with significant reduction of lipid peroxidation and free Fe(II) content. Taking together, our results indicate that long-term caffeine supplementation may exert preventive effects against oxidative stress and support the use of N. cinerea as an efficient alternative model to assess the efficacy of food molecules.

The Relationship Between Copper, Iron, and Selenium Levels and Alzheimer Disease.

This study aimed to evaluate the concentrations of copper, iron, and selenium in elderly people with Alzheimer disease (AD), comparing the same parameters in a paired group of healthy people, in order to verify if the amount of these metals may influence the cognitive impairment progression. Patients' cognitive impairment was evaluated by Clinical Dementia Rating (CDR). The elementary quantification of erythrocytes was performed by inductively coupled plasma mass spectrometry technique. The statistical analyses were carried out by SPSS software 20.0 version, employing Shapiro-Wilk, Wilcoxon, Kruskall-Wallis, and Spearman correlation tests, considering significant results of p < 0.05. The sample was composed of 34% (n = 11) of women and 66% (n = 21) of men in each group. The AD group was characterized by a higher concentration of copper (p < 0.0001) and iron (p < 0.0001); however, there is no significant difference in selenium level. The analyses of the metal levels in different stages of AD were not significant in CDR-1, however in CDR-2 and CDR-3, elevated levels of copper and iron were observed; in CDR-3 patients, the level of selenium was lower (p < 0.008) compared to that of healthy controls. Patients with Alzheimer disease studied present increase in biometal blood levels, especially of copper and iron, and such increase can be different according to the disease stage and can cause more impairment cognitive functions in AD.

Peumus boldus attenuates copper-induced toxicity in Drosophila melanogaster.

Peumus boldus (P. boldus) is a medicinal plant popularly used in the treatment of gastrointestinal disorders. P. boldus aqueous extract is rich in phenolic compounds and alkaloids that possess antiinflammatory and antioxidant effects. In the present study, the potential protective effect of P. boldus against Cu2+-induced toxicity was investigated. Adult Drosophila melanogaster were exposed to Cu2+ (1mM and 3mM) and/or P. boldus aqueous extract (5mg/mL) in the food during 4days. Cu2+-fed flies had impairment in the negative geotaxis performance (i.e. motor climbing capability) as well as a higher incidence of mortality when compared to the control group. P. boldus co-treatment afforded protection against the Cu2+-induced toxicity. Acetylcholinesterase (AChE) and glutathione S-transferase (GST) activity decreased significantly in D. melanogaster after Cu2+ exposure. P. boldus co-exposure for 4days restored enzyme activities to control levels. In addition, Cu2+ exposure caused a significant increase in the mRNA levels of antioxidant enzymes, superoxide dismutase (Sod1), catalase (Cat), thioredoxin reductase (TrxR1) and nuclear factor erythroid 2-related factor 2 (Nrf2), as well as increased the mRNA levels of acetylcholinesterase (Ace). The expression of P-type ATPase (Atp7A) and copper uptake protein 1 (Ctr1A) mRNAs were up-regulated in D. melanogaster exposed to Cu2+. The co-treatment with P. boldus blunted Cu2+-induced up-regulation of Atp7A and down-regulated Ctr1A mRNA expression. These findings suggest that P. boldus extracts reduce Cu2+-induced toxicity but not Cu2+ absorption in D. melanogaster. Consequently, P. boldus can be a potential therapeutical alternative for modulating Cu2+-associated toxicity.

Toxicity against Drosophila melanogaster and antiedematogenic and antimicrobial activities of Alternanthera brasiliana (L.) Kuntze (Amaranthaceae).

Bioactive phytocompounds are studied by several bioactivities demonstrated, as their cytotoxic effects. The aim of this work was to evaluate the phytochemical profile, the toxic effect using the Drosophila melanogaster animal model and the anti-inflammatory and antimicrobial effect of the Alternanthera brasiliana (EEAB) ethanol extract. The phytochemical profile was performed using HPLC. The cytotoxic effect was evaluated in vivo using D. melanogaster. The anti-inflammatory effect was determined by neurogenic and antiedematogenic assays, and the antimicrobial activity was assayed using a microdilution method to determine the minimum inhibitory concentration (MIC) of the EEAB alone and in association with antibiotics. The main compound identified on the EEAB was luteolin (1.93%). Its cytotoxic effect was demonstrated after 24 h in the concentrations of 10, 20 and 40 mg/mL. The extract demonstrated an antiedematogenic effect, with a reduction of the edema between 35.57 and 64.17%. The MIC of the extract was ≥1.024 µg/mL, thus being considered clinically irrelevant. However, when the EEAB was associated with gentamicin, a synergism against all bacterial strains assayed was observed: Staphylococcus aureus (SA10), Escherichia coli (EC06) and Pseudomonas aeruginosa (PA24). Due to these results, the EEAB demonstrated a low toxicity in vivo and anti-inflammatory and synergistic activities. These are promising results, mainly against microbial pathogens, and the compounds identified can be a source of carbon backbones for the discovery and creation of new drugs.

Antioxidant and mercury chelating activity of Psidium guajava var. pomifera L. leaves hydroalcoholic extract.

Mercury (Hg) is widely distributed in the environment and is known to produce several adverse effects in organisms. The aim of the present study was to examine the in vitro antioxidant activity and Hg chelating ability of the hydroalcoholic extract of Psidium guajava leaves (HEPG). In addition, the potential protective effects of HEPG against Hg(II) were evaluated using a yeast model (Saccharomyces cerevisiae). HEPG was found to exert significant antioxidant activity in 2,2-diphenyl-1-picrylhydrazyl scavenger and inhibition of lipid peroxidation induced by Fe(II) assays in a concentration-dependent manner. The extract also exhibited significant Hg(II) chelating activity. In yeast, Hg(II) induced a significant decrease in cell viability. In contrast, HEPG partially prevented the fall in cell viability induced by Hg(II). In conclusion, HEPG exhibited protective effects against Hg(II)-mediated toxicity, which may be related to both antioxidant and Hg(II)-chelating activities.

Safety assessment and antioxidant activity of Lantana montevidensis leaves: Contribution to its phytochemical and pharmacological activity.

Lantana camara, the widely studied species, and L. montevidensis, the less studied species of the genus Lantana are both used in traditional medicine for the same purpose (anti-asthma, anti-ulcer, anti-tumor, etc). However, little is known about the toxicity of L. montevidensis and there is limited information on its chemical constituents. Here, we investigated for the first time the genotoxicity and cytotoxicity of the ethanolic (EtOH) and aqueous extracts from the leaves of Lantana montevidensis in human leukocytes, as well as their possible interaction with human erythrocyte membranes in vitro. The antioxidant activities of both extracts were also investigated in chemical and biological models. Treatment of leukocytes with EtOH or aqueous extracts (1-480 µg/mL) did not affect DNA damage index, but promoted cytotoxicity at higher concentrations (240-480 µg/mL). Both extracts did not modify the osmotic fragility of human erythrocytes. The extracts scavenged DPPH radical and prevented Fe2+-induced lipid peroxidation in rat's brain and liver homogenates, and this was likely not attributed to Fe (II) chelation. The HPLC analysis of the extracts showed different amounts of polyphenolic compounds (isoquercitrin, gallic acid, catechin, ellagic acid, apigenin, kaempferol, caffeic acid, rutin, quercitrin, quercetin, chlorogenic acid, luteolin) that may have contributed to these effects. These results supported information on the functional use of L. montevidensis in folk medicine.

High-sucrose diet induces diabetic-like phenotypes and oxidative stress in Drosophila melanogaster: Protective role of Syzygium cumini and Bauhinia forficata.

Diet is a key component for development and longevity of organisms. Here, the fruit fly was used to evaluate the detrimental effects caused by consumption of high-sucrose diets (HSD), namely phenotypic responses linked to insulin signaling and oxidative stress. The protective effects of extracts from medicinal plants Syzygium cumini and Bauhinia forficata were investigated. HSD intake (15% and 30%) delayed the time to pupation and reduced the number of white pupae. In adult flies, the intake of diets was associated with mortality and increased levels of glucose+trehalose, triacylglycerols and hydrogen peroxide. Indeed, 30% HSD induced body-weight loss, mitochondrial dysfunction and changes in acetylcholinesterase, δ-aminolevulinate dehydratase and antioxidant enzymes activity. Catalase, superoxide dismutase, keap1, HSP70, dILP-5 and Insulin receptor mRNA levels were over-expressed in flies emerged from 30% HSD. The extract treatments blunted the developmental alterations elicited by diets. Syzygium cumini extract was more efficient than B. forficata in reducing hyperglycaemia, redox disturbances and the changes in mRNA expression of insulin receptor.

Cytotoxic and antioxidative potentials of ethanolic extract of Eugenia uniflora L. (Myrtaceae) leaves on human blood cells.

Eugenia uniflora is used in the Brazilian folk medicine to treat intestinal disorders and hypertension. However, scanty information exist on its potential toxicity to human, and little is known on its antioxidant activity in biological system. Hence, we investigated for the first time the potential toxic effects of ethanolic extract (EtOH) of E. uniflora (EEEU) in human leukocytes and erythrocytes, as well as its influence on membrane erythrocytes osmotic fragility. In addition, EEEU was chemically characterized and its antioxidant capacity was evaluated. We found that EEEU (1-480µg/mL) caused neither cytotoxicity nor DNA damage evaluated by Trypan blue and Comet assay, respectively. EEEU (1-480µg/mL) did not have any effect on membrane erythrocytes fragility. In addition, EEEU inhibited Fe2+-induced lipid peroxidation in rat brain and liver homogenates, and scavenged the DPPH radical. EEEU presented some polyphenolic compounds with high content such as quercetin, quercitrin, isoquercitrin, luteolin and ellagic acid, which may be at least in part responsible for its beneficial effects. Our results suggest that consumption of EEEU at relatively higher concentrations may not result in toxicity. However, further in vitro and in vivo studies should be conducted to ascertain its safety.

Selenium and mercury levels in rat liver slices co-treated with diphenyl diselenide and methylmercury.

Organoseleno-compounds have been investigated for its beneficial effects against methylmercury toxicity. In this way, diphenyl diselenide (PhSe)2 was demonstrated to decrease Hg accumulation in mice, protect against MeHg-induced mitochondrial dysfunction, and protect against the overall toxicity of this metal. In the present study we aimed to investigate if co-treatment with (PhSe)2 and MeHg could decrease accumulation of Hg in liver slices of rats. Rat liver slices were co-treated with (PhSe)2 (0.5; 5 µM) and/or MeHg (25 µM) for 30 min at 37 °C and Se and Hg levels were measured by inductively coupled plasma mass spectrometry (ICP-MS) in the slices homogenate, P1 fraction, mitochondria and incubation medium. Co-treatment with (PhSe)2 and MeHg did not significantly alter Se levels in any of the samples when compared with compounds alone. In addition, co-treatment with (PhSe)2 and MeHg did not decrease Hg levels in any of the samples tested, although, co-incubation significantly increased Hg levels in homogenate. We suggest here that (PhSe)2 could exert its previously demonstrated protective effects not by reducing MeHg levels, but forming a complex with MeHg avoiding it to bind to critical molecules in cell.

Effect of antioxidant potential on severity of cirrhosis in humans / Efecto del potencial antioxidante para las complicaciones de la cirrosis en los seres humanos

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 (AU)

Introducción/Objetivos: examinar la relación entre los potenciales antioxidantes y los parámetros de gravedad de la cirrosis en los seres humanos. Métodos: quince pacientes con cirrosis hepática (nueve sujetos - grupo Child B, y seis sujetos - grupo Child C) y nueve sujetos control fueron incluidos en el estudio. Los principales criterios que se tuvieron en cuenta para caracterizar el diagnóstico de la cirrosis y sus complicaciones fueron la AST: relación de ALT, AST índice de la relación de plaquetas, clasificación Bonacini, clasificación MELD y clasificación de Child. Estos parámetros fueron determinados con base en los resultados de laboratorio y los registros clínicos del paciente. Se midieron los niveles de Zn, ácido ascórbico (AA) y los parámetros de estrés oxidativo en muestras de sangre de pacientes cirróticos. Resultados: el análisis de los niveles plasmáticos de Se y AA mostraron bajas concentraciones en los pacientes cirróticos en comparación con los sujetos control (P < 0,05); sin embargo, hubo una correlación positiva entre el plasma de Se y los parámetros de gravedad de la cirrosis en pacientes del grupo Child B y C. En la actividad de las enzimas antioxidantes catalasa solamente fue menor en los pacientes del grupo Child C, en comparación con el grupo control. Conclusión: se encontraron niveles bajos en plasma de Se y AA en pacientes cirróticos. Sin embargo, no está claro por qué los niveles de selenio tienden a aumentar con la gravedad de la cirrosis hepática (AU)

Oxidative stress by Haemonchus contortus in lambs: Influence of treatment with zinc edetate.

The aim of the present study was to assess the effects of zinc edetate on the oxidative stress of lambs infected by Haemonchus contortus. Twenty-four lambs were allocated into four groups: Group I--uninfected animals; Group II--uninfected animals treated subcutaneously with zinc edetate; Group III--animals infected by H. contortus and Group IV--animals infected and treated. The oxidative stress index (OSI) and the eggs per gram of feces (EPG) were assessed after 10, 17, 24, 31 and 38 days post-infection. Based on the EPG and the quantity of adult H. contortus, the infection did not differ between groups III and IV. Zinc edetate reduced the OSI in Group IV in relation to Group I after 24 days post-infection, and in relation to group III after 31 days post-infection. Treatment with zinc edetate could help reduce the oxidative stress induced by H. contortus in lambs.

Polyphenolic Composition and Evaluation of Antioxidant Activity, Osmotic Fragility and Cytotoxic Effects of Raphiodon echinus (Nees & Mart.) Schauer.

Raphiodon echinus (R. echinus) is used in Brazilian folk medicine for the treatment of inflammation, coughs, and infectious diseases. However, no information is available on the potential antioxidant, cytotoxicity and genotoxicity of this plant. In this study, the polyphenolic constituents, antioxidant capacity and potential toxic effects of aqueous and ethanolic extracts of R. echinus on human erythrocytes and leukocytes were investigated for the first time. R. echinus extracts showed the presence of Gallic, chlorogenic, caffeic and ellagic acids, rutin, quercitrin and quercetin. Aqueous and ethanolic extracts of R. echinus exhibited antioxidant activity in DPPH radical scavenging with IC50 = 111.9 µg/mL (EtOH extract) and IC50 = 227.9 µg/mL (aqueous extract). The extracts inhibited Fe(2+) (10 µM) induced thiobarbituric acid reactive substances (TBARS) formation in rat brain and liver homogenates. The extracts (30-480 µg/mL) did not induce genotoxicity, cytotoxicity or osmotic fragility in human blood cells. The findings of this present study therefore suggest that the therapeutic effect of R. echinus may be, in part, related to its antioxidant potential. Nevertheless, further in vitro and in vivo studies are required to ascertain the safety margin of its use in folk medicine.

Protein profile of lambs experimentally infected with Haemonchus contortus and supplemented with selenium and copper.

BACKGROUND: Gastrointestinal nematodes cause significant economic losses in the sheep industry, with frequent reports of anthelmintic resistance. Therefore, alternative methods to control these parasites are necessary. Thus, the aim of the present study was to assess the effect of treatment with selenium and copper on the protein profile of sheep that were experimentally infected with Haemonchus contortus. METHODS: Twenty-eight lambs were experimentally infected with H. contortus and divided into four experimental groups as follow: G1--untreated animals; G2--treated with sodium selenite; G3--treated with copper; G4--treated with sodium selenite and copper. The serum protein, body weight and egg count per gram of feces (EPG) were assessed at the baseline and after 20, 40, 60 and 80 days. The parasite burden was assessed 80 days after the beginning of the experiment. RESULTS: Higher levels of total protein and gamma globulin were observed in the lambs treated with sodium selenite and copper on D80. Copper acted as a growth promoter. The copper-supplemented groups exhibited higher daily and total weight gain. The association of selenium and copper altered the protein profile of sheep. Copper and selenium supplementation reduced EPG and worm burden at the end of the experiment. To the best of our knowledge, this is the first study to demonstrate the positive effect of the combined parenteral supplementation of Se and Cu on H. contortus infection. CONCLUSIONS: This injectable supplementation could be used as an auxiliary method to control H. contortus in sheep.