The interplay between the inoculation of plant growth-promoting rhizobacteria and the rhizosphere microbiome and their impact on plant phenotype.

Microbial inoculation stands as a pivotal strategy, fostering symbiotic relationships between beneficial microorganisms and plants, thereby enhancing nutrient uptake, bolstering resilience against environmental stressors, and ultimately promoting healthier and more productive plant growth. However, while the advantageous roles of inoculants are widely acknowledged, the precise and nuanced impacts of inoculation on the intricate interactions of the rhizosphere microbiome remain significantly underexplored. This study explores the impact of bacterial inoculation on soil properties, plant growth, and the rhizosphere microbiome. By employing various bacterial strains and a synthetic community (SynCom) as inoculants in common bean plants, the bacterial and fungal communities in the rhizosphere were assessed through 16 S rRNA and ITS gene sequencing. Concurrently, soil chemical parameters, plant traits, and gene expression were evaluated. The findings revealed that bacterial inoculation generally decreased pH and V%, while increasing H+Al and m% in the rhizosphere. It also decreased gene expression in plants related to detoxification, photosynthesis, and defense mechanisms, while enhancing bacterial diversity in the rhizosphere, potentially benefiting plant health. Specific bacterial strains showed varied impacts on rhizosphere microbiome assembly, predominantly affecting rhizospheric bacteria more than fungi, indirectly influencing soil conditions and plants. Notably, Paenibacillus polymyxa inoculation improved plant nitrogen (by 5.2%) and iron levels (by 28.1%), whereas Bacillus cereus boosted mycorrhization rates (by 70%). Additionally, inoculation led to increased complexity in network interactions within the rhizosphere (∼15%), potentially impacting plant health. Overall, the findings highlight the significant impact of introducing bacteria to the rhizosphere, enhancing nutrient availability, microbial diversity, and fostering beneficial plant-microbe interactions.

Genomic insights of Fictibacillus terranigra sp. nov., a versatile metabolic bacterium from Amazonian Dark Earths.

The Amazon rainforest, a hotspot for biodiversity, is a crucial research area for scientists seeking novel microorganisms with ecological and biotechnological significance. A key region within the Amazon rainforest is the Amazonian Dark Earths (ADE), noted for supporting diverse plant and microbial communities, and its potential as a blueprint for sustainable agriculture. This study delineates the isolation, morphological traits, carbon source utilization, and genomic features of Fictibacillus terranigra CENA-BCM004, a candidate novel species of the Fictibacillus genus isolated from ADE. The genome of Fictibacillus terranigra was sequenced, resulting in 16 assembled contigs, a total length of 4,967,627 bp, and a GC content of 43.65%. Genome annotation uncovered 3315 predicted genes, encompassing a wide range of genes linked to various metabolic pathways. Phylogenetic analysis indicated that CENA-BCM004 is a putative new species, closely affiliated with other unidentified Fictibacillus species and Bacillus sp. WQ 8-8. Moreover, this strain showcased a multifaceted metabolic profile, revealing its potential for diverse biotechnological applications. It exhibited capabilities to antagonize pathogens, metabolize multiple sugars, mineralize organic matter compounds, and solubilize several minerals. These insights substantially augment our comprehension of microbial diversity in ADE and underscore the potential of Fictibacillus terranigra as a precious resource for biotechnological endeavors. The genomic data generated from this study will serve as a foundational resource for subsequent research and exploration of the biotechnological capabilities of this newly identified species.

Draft genome sequences of representative Paenibacillus polymyxa, Bacillus cereus, Fictibacillus sp., and Brevibacillus agri strains isolated from Amazonian dark earth.

Here, we report 10 distinct bacterial genomes from Amazonian dark earths, including six identified as Paenibacillus polymyxa, while the remaining four were unique representatives of Paenibacillus vini, Bacillus cereus, Brevibacillus agri, and Fictibacillus sp., respectively. Each strain exhibited antagonistic activity against Fusarium oxysporum, underscoring their potential as sustainable agriculture resources.

Aging: silencing the PKA and AkT/PKB signaling pathways alters the antioxidant capacity of resveratrol.

One of the theories related to aging is the increase in oxidative stress. Given this, the objective of the study is to evaluate the cellular mechanisms responsible for the resveratrol antioxidant effect on leukocytes from donors aged between 20 and 80 years old. For this, leukocytes from donors of three age groups (20-39, 40-59 and 60-80) were isolated. Image-iT™LIVE Green Reactive Oxygen Species (ROS) Kit was used. Reactive Nitrogen Species (RNS) analysis was performed by measuring nitric oxide and peroxynitrite. The PKA, Akt/PKB and p38-MAPK were evaluated by chemiluminescence. The statistical analysis between age and treatments were performed by Pearson correlation (*p < 0.05). It was possible to observe the antioxidant effect of resveratrol in all age groups. The correlation results show loss of resveratrol effect in decreasing ROS in leukocytes from older donors. We observed an active antioxidant effect of p38-MAPK in all ages, with resveratrol acting on it. The PKA and Akt/PKB were active in leukocytes from donors aged 20-59. In cells from donors older than 60, these pathways are silenced, and an effect is also not observed in cells treated with resveratrol. Therefore, resveratrol showed antioxidant effect in all age, although it was more pronounced in leukocytes from younger. One of resveratrol's mechanisms is due to the activation of the PKA and Akt/PKB, which were activated in younger donor cells.

Microbial metabolic activity in Amazon floodplain forest and agricultural soils.

Microorganisms play an essential role in ecosystem functions. An increasingly used method for conducting functional analyses of a soil microbial community is based on the physiological profile at the community level. This method allows the metabolic capacity of microorganisms to be assessed based on patterns of carbon consumption and derived indices. In the present study, the functional diversity of microbial communities was assessed in soils from seasonally flooded-forest (FOR) and -traditional farming systems (TFS) in Amazonian floodplains flooded with black, clear, and white water. The soils of the Amazon floodplains showed differences in the metabolic activity of their microbial communities, with a general trend in activity level of clear water floodplain > black water floodplain > white water floodplain. The redundancy analysis (RDA) indicated that soil moisture (flood pulse) was the most important environmental parameter in determining the metabolic activity of the soil microbial communities in the black, clear, and white floodplains. In addition, the variance partitioning analysis (VPA) indicated that the microbial metabolic activity of the soil was more influenced by water type (41.72%) than by seasonality (19.55%) and land use type (15.28%). The soil microbiota of the white water floodplain was different from that of the clear water and black water floodplains in terms of metabolic richness, as the white water floodplain was mainly influenced by the low substrate use during the non-flooded period. Taken together, the results show the importance of considering soils under the influence of flood pulses, water types, and land use as environmental factors when recognizing functional diversity and ecosystem functioning in Amazonian floodplains.

Aging: Change in SIRT1 and Enzymatic Profile Promotes a Decrease in the Antioxidant Capacity of Resveratrol in Human Leukocytes In Vitro.

BACKGROUND: One of the most studied theories about aging comes from the accumulation of free radical generation, leading to oxidative stress. Resveratrol (RSV) is a polyphenolic compound that has been shown to act as an antioxidant in medical practice. OBJECTIVE: To verify the antioxidant action of resveratrol (and its correlation with aging) in leukocytes from donors of different ages, mainly through the analysis of the three main enzymes of the antioxidant complex and the analysis of the SIRT1 signaling pathway. METHODS: Luminol-dependent chemiluminescence assay was used to evaluate ROS and SIRT1. Antioxidant enzymes were evaluated by commercial kits. *p<0.05. RESULTS: In all age groups, there was a reduction in reactive oxygen species (ROS) in cells stimulated with RSV. There was a positive correlation between its antioxidant effect and donor age. In younger individuals (20-39 years old), there was an increase in catalase activity in cells exposed to RSV. In the older groups (40-59 years old and 60-80 years old), RSV was able to increase the activity of the enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx). Through the analysis of SIRT1 it was possible to observe a silencing of the pathway in leukocytes treated with RSV during aging. CONCLUSION: RSV showed antioxidant activity in all age groups, although more pronounced in younger individuals. One of the mechanisms of action of the RSV is due to the increase in the activity of antioxidant enzymes, which varies according to the individual's age, especially through the modulation of important antioxidant pathways.

Resveratrol has its antioxidant and anti-inflammatory protective mechanisms decreased in aging.

In the elderly, there is an increase in oxidative and inflammatory activity. Resveratrol (RSV) is a polyphenol that has several proven biological activities, such as antioxidant and anti-inflammatory. Thus, the aim of our study was to verify the possible antioxidant and anti-inflammatory effects of RSV on human mononuclear cells (PBMCs) from donors aged between 40 and 59 and 60-80 years old. For this, 6-8 patients were selected by age group. Cells were isolated and divided into 4 groups: Control (C), RSV only, H2O2 (to induce an oxidizing environment - C+) and H2O2+RSV. The quantification of reactive nitrogen species (NO and ONOO-), as well as pro and anti-inflammatory cytokines (TNFα, IL-6 and IL-10) was performed. Pearson's correlation and comparison between groups were performed (p<0.05). Our results showed a greater role of RSV in the middle-aged compared to the elderly group, in relation to the balance of NO/ONOO- and the levels of cytokines IL-6 and TNFα. It was also possible to observe an improvement in the anti-inflammatory profile in both age groups, but more effective in the cells in the middle-aged group. Thus, we could observe that RSV has better activity in the reduction of important biomarkers of oxidation and inflammation.

The preventive use of resveratrol increases its antioxidant effect by SIRT1 and subclinical anti-inflammatory action in Neuro-2A cells.

Currently, the important role of oxidative stress in the aging process and in neurodegenerative diseases has been highlighted, suggesting the beneficial effect of antioxidants as adjuvant therapy. Resveratrol (RSV) is a polyphenolic compound used in the clinic and has been shown as an antioxidant and anti-inflammatory. Therefore, the objective was to verify neuroprotective and modulating effects of RSV on N2-A cells, pre or post inserted into an oxidative stress environment. For this, two treatment conditions were established: pre-stimulus and post-stimulus. The analysis of AMPK and SIRT1 cell signaling pathways was performed through the chemiluminescence assay using the dorsomorphin and EX527 inhibitors, respectively. The inflammatory profile was also evaluated in these neural cells, through the levels of IL-6, TNF, and IL-10. We observed that RSV in N2-A cells has anti-inflammatory effect and antioxidant property and it mechanism is dependent on the SIRT1 signaling pathway. RSV effects occurs most markedly when cells have been pre-stimulated before inducing an oxidative stress environment. These results are important for conducting more adequate protocols in the medical and nutritional clinic.

Ecological co-occurrence and soil physicochemical factors drive the archaeal community in Amazonian soils.

We evaluated the co-occurrence of archaeal taxonomic groups and soil physicochemical characteristics in relation to the structuring of the archaeal community in Amazonian soil under different land use systems. Soil samples were collected in primary forest (PF), secondary forest (SF), agricultural systems (AG) and cattle pastures (PA). Archaeal community composition was revealed based on high-throughput amplicon sequencing of the 16S rRNA gene. The results revealed co-occurrence of archaeal classes, with two groups formed: Thaumarchaeota classes, including South Africa Gold Mine-Group 1 (SAGMG-1), Crenarchaeotic group (SCG) and Crenarchaeota candidate division YNPFFA, with predominance in PF and SF; and Bathyarchaeota_unclassified, Methanomicrobia and Methanobacteria (Euryarchaeota) with the FHMa11 terrestrial group, with predominance in PA. The number of co-occurrences between groups was lower in SF, AG and PA (approximately 30%) than in PF. The qPCR analysis revealed that PF also had the largest number of archaeal representatives. Soil texture may be a limiting factor of interactions between groups since the most representative groups, SAGMG-1 and the SCG (over 20% in all sites), were positively associated with coarse sand, the soil factor most correlated with the groups (33% of the total). These results suggest that interactions between archaeal classes belonging to different phyla may be dependent on the number of individuals in the soil environment. In this context, differences in soil physical structure among the land use systems can reduce the representatives of key groups and consequently the co-occurrence of Archaea, which could compromise the natural dynamics of this complex environment.

Development of an Index for the Inspection of Aedes aegypti Breeding Sites in Brazil: Multi-criteria Analysis.

BACKGROUND: Aedes aegypti is a vector for the transmission of diseases such as dengue fever, chikungunya, Zika fever, and yellow fever. In 2016, over 1 million cases of these diseases were reported in Brazil, which is an alarming public health issue. One of the ways of controlling this disease is by inspecting and neutralizing the places where A. aegypti lays its eggs. The Ministry of Planning, Development, and Administration of Brazil maintains the inspection statistics. OBJECTIVE: We propose a multi-criteria analysis to create an index for A. aegypti inspections reported through the Ministry of Planning, Development, and Administration system of Brazil. METHODS: Based on the repository from urban cleaning services combined with data on inspections conducted by government agencies in several Brazilian cities and municipalities, we selected and combined metrics, which we further ranked using the analytic hierarchy process methodology. We also developed risk maps based on the analytic hierarchy process ranking of the A. aegypti breeding sites. RESULTS: Based on our analysis and the available data, the priority for inspections should consider the number of sick people (weight 0.350), medical evaluations (weight 0.239), inspections (weight 0.201), mosquito breeding sites (weight 0.126), and days of absence from work (weight 0.096). CONCLUSIONS: The proposed index could aid public health practitioners in preventing the appearance of new A. aegypti breeding sites. This information technology application can help solve such public health challenges.

Resveratrol: Change of SIRT 1 and AMPK signaling pattern during the aging process.

One of the causes for aging is free radical damage. Resveratrol (RSV), a polyphenolic compound has been shown to act as an antioxidant and anti-inflammatory. The objective this study was to verify in an oxidative stress environment in Human Mononuclear cells from Middle aged and Elderly donors, the existence of a change in the SIRT1 and AMPK signaling pattern by RSV. In both age groups there was a reduction in reactive oxygen species (ROS) in cells stimulated with RSV. It was observed that in the Elderly group there was a higher production of ROS and that the reduction from RSV was smaller compared to the other group. There was an increased activity of Superoxide Dismutase in cells exposed to RSV in the elderly group. It was observed that for the Middle Aged group, SIRT 1 and AMPK are antioxidant pathways and RSV acts via SIRT1. In the elderly, the SIRT1 remains antioxidant and RSV ceases its operation via SIRT1. RSV has an antioxidant action in both age groups, and that in aging there was a change in the cellular context characterized by the silencing of the AMPK pathway antioxidant character.

Antioxidant effect of Resveratrol: Change in MAPK cell signaling pathway during the aging process.

Aging is characterized by a progressive loss of physiological integrity. One common denominator is the increase of reactive oxygen species (ROS) caused by inhibition of important antioxidant pathways. Resveratrol is a polyphenol known for its potent antioxidant activity. However, antioxidant pathways activated by them change with aging. The objective of our study was to verify the antioxidant effect of resveratrol in an oxidative stress environment in Human Mononuclear Cells (PBMC) from donors with different ages. Resveratrol (5 µM), a stimulus with H2O2 (0,64 % v/v) in addition to inhibitors of PKA, AkT/PKB and MAPK signaling pathways were used in chemiluminescence assay. An incresed basal production of ROS was observed in the elderly than in the middle-aged group. Resveratrol was able to reduce ROS in both groups, but with greater efficiency in the middle-aged group. By inhibiting PKA, Akt/PKB and MAPK signaling pathways we observed that resveratrol presented an altered performance in the aging process, changing signaling pattern of MAPK pathway.

Resistance Breeding of Common Bean Shapes the Physiology of the Rhizosphere Microbiome.

The taxonomically diverse rhizosphere microbiome contributes to plant nutrition, growth and health, including protection against soil-borne pathogens. We previously showed that breeding for Fusarium-resistance in common bean changed the rhizosphere microbiome composition and functioning. Here, we assessed the impact of Fusarium-resistance breeding in common bean on microbiome physiology. Combined with metatranscriptome data, community-level physiological profiling by Biolog EcoPlate analyses revealed that the rhizosphere microbiome of the Fusarium-resistant accession was distinctly different from that of the Fusarium-susceptible accession, with higher consumption of amino acids and amines, higher metabolism of xylanase and sialidase, and higher expression of genes associated with nitrogen, phosphorus and iron metabolism. The resistome analysis indicates higher expression of soxR, which is involved in protecting bacteria against oxidative stress induced by a pathogen invasion. These results further support our hypothesis that breeding for resistance has unintentionally shaped the assembly and activity of the rhizobacterial community toward a higher abundance of specific rhizosphere competent bacterial taxa that can provide complementary protection against fungal root infections.

Acidobacteria Subgroups and Their Metabolic Potential for Carbon Degradation in Sugarcane Soil Amended With Vinasse and Nitrogen Fertilizers.

Acidobacteria is a predominant bacterial phylum in tropical agricultural soils, including sugarcane cultivated soils. The increased need for fertilizers due to the expansion of sugarcane production is a threat to the ability of the soil to maintain its potential for self-regulation in the long term, in witch carbon degradation has essential role. In this study, a culture-independent approach based on high-throughput DNA sequencing and microarray technology was used to perform taxonomic and functional profiling of the Acidobacteria community in a tropical soil under sugarcane (Saccharum spp.) that was supplemented with nitrogen (N) combined with vinasse. These analyses were conducted to identify the subgroup-level responses to chemical changes and the carbon (C) degradation potential of the different Acidobacteria subgroups. Eighteen Acidobacteria subgroups from a total of 26 phylogenetically distinct subgroups were detected based on high-throughput DNA sequencing, and 16 gene families associated with C degradation were quantified using Acidobacteria-derived DNA microarray probes. The subgroups Gp13 and Gp18 presented the most positive correlations with the gene families associated with C degradation, especially those involved in hemicellulose degradation. However, both subgroups presented low abundance in the treatment containing vinasse. In turn, the Gp4 subgroup was the most abundant in the treatment that received vinasse, but did not present positive correlations with the gene families for C degradation analyzed in this study. The metabolic potential for C degradation of the different Acidobacteria subgroups in sugarcane soil amended with N and vinasse can be driven in part through the increase in soil nutrient availability, especially calcium (Ca), magnesium (Mg), potassium (K), aluminum (Al), boron (B) and zinc (Zn). This soil management practice reduces the abundance of Acidobacteria subgroups, including those potentially involved with C degradation in this agricultural soil.

Baccharis trimera (Carqueja) Improves Metabolic and Redox Status in an Experimental Model of Type 1 Diabetes.

Diabetes mellitus is a metabolic disorder that causes severe complications due to the increased oxidative stress induced by disease. Many plants are popularly used in the treatment of diabetes, e.g., Baccharis trimera (carqueja). The aim of this study was to explore the potential application of the B. trimera hydroethanolic extract in preventing redox stress induced by diabetes and its hypoglycemic properties. Experiments were conducted with 48 female rats, divided into 6 groups, named C (control), C600 (control + extract 600 mg/kg), C1200 (control + extract 1200 mg/kg), D (diabetic), D600 (diabetic + 600 mg/kg), and D1200 (diabetic + 1200 mg/kg). Type 1 diabetes was induced with alloxan, and the animals presented hyperglycemia and reduction in insulin and body weight. After seven days of experimentation, the nontreated diabetic group showed changes in biochemical parameters (urea, triacylglycerol, alanine aminotransferase, and aspartate aminotransferase) and increased carbonyl protein levels. Regarding the antioxidant enzymes, an increase in superoxide dismutase activity was observed but in comparison a decrease in catalase and glutathione peroxidase activity was noted which suggests that diabetic rats suffered redox stress. In addition, the mRNA of superoxide dismutase, catalase, and glutathione peroxidase enzymes were altered. Treatment of diabetic rats with B. trimera extract resulted in an improved glycemic profile and liver function, decreased oxidative damage, and altered the expression of mRNA of the antioxidants enzymes. These results together suggest that B. trimera hydroethanolic extract has a protective effect against diabetes.

Baccharis trimera inhibits reactive oxygen species production through PKC and down-regulation p47 phox phosphorylation of NADPH oxidase in SK Hep-1 cells.

Baccharis trimera, popularly known as "carqueja", is a native South-American plant possessing a high concentration of polyphenolic compounds and therefore high antioxidant potential. Despite the antioxidant potential described for B. trimera, there are no reports concerning the signaling pathways involved in this process. So, the aim of the present study was to assess the influence of B. trimera on the modulation of PKC signaling pathway and to characterize the effect of the nicotinamide adenine dinucleotide phosphate oxidase enzyme (NOX) on the generation of reactive oxygen species in SK Hep-1 cells. SK-Hep 1 cells were treated with B. trimera, quercetin, or rutin and then stimulated or not with PMA/ionomycin and labeled with carboxy H2DCFDA for detection of reactive oxygen species by flow cytometer. The PKC expression by Western blot and enzyme activity was performed to evaluate the influence of B. trimera and quercetin on PKC signaling pathway. p47 phox and p47 phox phosphorylated expression was performed by Western blot to evaluate the influence of B. trimera on p47 phox phosphorylation. The results showed that cells stimulated with PMA/ionomycin (activators of PKC) showed significantly increased reactive oxygen species production, and this production returned to baseline levels after treatment with DPI (NOX inhibitor). Both B. trimera and quercetin modulated reactive oxygen species production through the inhibition of PKC protein expression and enzymatic activity, also with inhibition of p47 phox phosphorylation. Taken together, these results suggest that B. trimera has a potential mechanism for inhibiting reactive oxygen species production through the PKC signaling pathway and inhibition subunit p47 phox phosphorylation of nicotinamide adenine dinucleotide phosphate oxidase.

Representações sociais sobre a doença de mulheres acometidas do câncer cervico-uterino / Representaciones sociales acerca de la enfermedad de las mujeres con cáncer cérvico-uterino / Social representations about the disease of women with cervico-uterine cancer

Objective: understanding the social representation of women about cervical cancer and its implications for care of themselves. Method: this is a qualitative study of a descriptive approach that used as a theoretical role the social representations, taking the interview as a technique for data collection of information. We worked with 35 outpatient women of a referral public hospital in oncology. Results: within the dialogs it was observed that the concept of cervical cancer was closely related to the feeling factor, leading fear and sadness. The evidences also showed that women focused on sexuality and treatment as a life change along the disease. Conclusion: cancer of the cervix produces a great change of life in women who passed through the problem, not just by the physical factors, but quite by the subjective side in fighting the disease.

Objetivo: compreender a representação social de mulheres com câncer de colo de útero e suas implicações para o cuidado de si. Método: um estudo de natureza qualitativa e abordagem descritiva que utilizou como aporte teórico as representações sociais, tendo a entrevista como técnica de coleta de dados das informações. Trabalhamos com 35 mulheres do ambulatório de um hospital público de referência em oncologia. Resultados: dentre os discursos observou-se que o conceito de câncer de colo de útero foi muito relacionado com o fator sentimental, imperando o medo e a tristeza. Os depoimentos mostraram também que as mulheres focaram a sexualidade e o tratamento como mudança de vida no decorrer da doença.Conclusão: o câncer de colo de útero gera uma grande mudança de vida nas mulheres que passam pelo problema, não apenas pelo fator físico, mas muito pelo lado subjetivo no enfrentamento da doença.

Objetivo: comprender la representación social de las mujeres acerca del cáncer cervical y sus implicaciones para el cuidado de sí mismas. Método: este estudio cualitativo de enfoque descriptivo utilizó como aporte teórico las representaciones sociales, tomando la entrevista como técnica de recolección de datos de la información. Trabajamos con 35 mujeres del ambulatorio de un hospital público de referencia en oncología. Resultados: entre los discursos se observó que el concepto de cáncer cervical de útero estaba realmente relacionado con el factor sentimental, que reina el miedo y la tristeza. Los testimonios también mostraron que las mujeres se centraron en la sexualidad y el tratamiento como un cambio de vida ya que la enfermedad avanzaba. Conclusión: el cáncer del cuello del útero produce un gran cambio de vida en las mujeres que pasan por el problema, no sólo por factores físicos, sino todo el aspecto subjetivo en la lucha contra la enfermedad.

Protective effect of Baccharis trimera extract on acute hepatic injury in a model of inflammation induced by acetaminophen.

BACKGROUND: Acetaminophen (APAP) is a commonly used analgesic and antipyretic. When administered in high doses, APAP is a clinical problem in the US and Europe, often resulting in severe liver injury and potentially acute liver failure. Studies have demonstrated that antioxidants and anti-inflammatory agents effectively protect against the acute hepatotoxicity induced by APAP overdose. METHODS: The present study attempted to investigate the protective effect of B. trimera against APAP-induced hepatic damage in rats. The liver-function markers ALT and AST, biomarkers of oxidative stress, antioxidant parameters, and histopathological changes were examined. RESULTS: The pretreatment with B. trimera attenuated serum activities of ALT and AST that were enhanced by administration of APAP. Furthermore, pretreatment with the extract decreases the activity of the enzyme SOD and increases the activity of catalase and the concentration of total glutathione. Histopathological analysis confirmed the alleviation of liver damage and reduced lesions caused by APAP. CONCLUSIONS: The hepatoprotective action of B. trimera extract may rely on its effect on reducing the oxidative stress caused by APAP-induced hepatic damage in a rat model. General Significance. These results make the extract of B. trimera a potential candidate drug capable of protecting the liver against damage caused by APAP overdose.

Alternative methods in toxicity testing: the current approach

Alternative methods are being developed to reduce, refine, and replace (3Rs) animals used in experiments, aimed at protecting animal welfare. The present study reports alternative tests which are based on the principles of the 3Rs and the efforts made to validate these tests. In Europe, several methodologies have already been implemented, such as tests of irritability, cell viability, and phototoxicity as well as in vitro mathematical models together with the use of in silico tools. This is a complex process that spans from development to regulatory approval and subsequent adoption by various official entities. Within this regulatory framework is REACH, the European Community Regulation for chemicals and their safe use. In Brazil, the BraCVAM (Brazilian Center for the Validation of Alternative Methods) was recently established to validate alternative methods and stimulate incorporation of new methodologies. A new vision of toxicology is emerging for the 21st century (Tox-21), and the subsequent changes are shaping a new paradigm.

Métodos alternativos estão sendo desenvolvidos para a redução, o refinamento e a substituição (3R) do número de animais utilizados em experimentos, visando ao seu bem-estar. Esses testes alternativos baseiam-se no princípio dos 3R e esforços têm sido empregados para que sejam validados. Na Europa, diversas metodologias já foram implantadas tais como: testes de irritabilidade, testes de viabilidade celular, testes de fototoxicidade e modelos matemáticos in vitro, além do uso de ferramentas in silico. Esse é um processo complexo, que abrange desde o seu desenvolvimento até a aceitação regulatória e posterior adoção por diversas organizações oficiais. No contexto regulatório está o REACH, o Regulamento da Comunidade Européia, para produtos químicos e sua utilização segura. No Brasil, o BraCVAM (Centro Brasileiro de Validação de Métodos Alternativos) foi recentemente estabelecido para validação de métodos alternativos e estímulo à incorporação de novas metodologias. Uma nova visão de toxicologia vem surgindo para o século XXI (Tox-21) e as mudanças ocasionadas promoverão um novo paradigma.

Baccharis trimera improves the antioxidant defense system and inhibits iNOS and NADPH oxidase expression in a rat model of inflammation.

Acetaminophen is a common analgesic and antipyretic compound which, when administered in high doses, has been associated with significant morbidity and mortality, secondary to hepatic toxicity. Although this may be due to a direct interaction of reactive acetaminophen metabolites with hepatocyte proteins, recent studies have suggested that reactive species produced by neutrophils also contribute to the pathophysiological process. Researches on the chemical composition of B. trimera show that this plant has bioactive compounds such as flavonoids, related to the organism's protection against free radicals. Therefore, in the present study, using Fischer rats, the effect of B. trimera on the antioxidant defense system, the production of nitric oxide (NO) and on the expression of nitric oxide synthase (iNOS), superoxide dismutase (SOD), catalase (CAT) and of the subunits of the NADPH oxidase in neutrophils was evaluated in a model of phagocytosis induced by zimosan (ZC3b) and in a model of inflammation induced by acetaminophen. The results show that the treatment with B. trimera improves the defense system of antioxidant and restores the balance ROS / NO that is altered in the inflammatory process induced by APAP. In conclusion, B. trimera extracts exert antioxidant properties by scavenging ROS and decrease the expression of genes responsible by reactive species production in neutrophils.