The present study aimed to evaluate the redox activity of Vernonanthura polyanthes leaf aqueous extract (VpLAE) and its n-butanol fraction (n-BF) in mouse liver in the absence or in the presence of doxorubicin (DXR). For this, the concentration of malondialdehyde (MDA), the activities of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and glutathione peroxidase (GPx) were determined in the liver of Swiss Webster mice (n = 5 animals per group). Immunohistochemical analyses on hepatocytes labeled with anti-4-hydroxynonenal (4HNE) were also performed to confirm the decrease in lipid peroxidation in animals treated with DXR and VpLAE or n-BF. MDA levels and GST activity increased in the livers of mice that received just VpLAE at a dose of 1000 mg/kg compared with the negative control. Moreover, n-BF alone increased CAT activity at 250 mg/kg, SOD and GST at 1000 mg/kg, and MDA at 250, 500, and 1000 mg/kg. These data indicate that VpLAE or n-BF alone can promote oxidative stress in hepatocytes. In contrast, when VpLAE was associated with DXR in a pre-treatment regimen, or when n-BF was associated with DXR in co- or pre-treatment regimens, MDA levels decreased, suggesting a protective effect against DXR-induced damage. The decrease in 4HNE labeling in the livers of mice treated with DXR and VpLAE or n-BF confirmed that pre-treatment with VpLAE or pre- and co-treatments with n-BF reduced DXR-induced lipid peroxidation. In conclusion, VpLAE and n-BF could present a dual behavior, promoting oxidative stress in hepatocytes in the absence of DXR or reducing oxidative stress in the livers of mice treated with DXR. This shift in perspective motivates future studies of VpLAE and n-BF as promising candidates to overcome DXR-induced hepatotoxicity.

Blue light-induced retinopathy is a sight-threatening condition which leads to chronic parainflammation, in which retinal pigment epithelium (RPE) dysfunction plays a critical role. While the complement system and the inflammatory cytokine IL-17A are implicated in its pathogenesis, their precise interplay within the RPE, along with the role of the immunomodulatory aryl hydrocarbon receptor (AhR), remains unclear. To address this gap, we investigated the interaction between AhR, the complement system, and IL-17A in RPE inflammation using an in vivo mouse model involving chronic low-intensity blue light exposure (300 Lux, 12 h/day for 35 days) and an in vitro system with human ARPE-19 cells (wild-type and AhR-knockout). We found that blue light exposure increased retinal C3, C5, and IL-17A while downregulating AhR. In cell cultures, treatment with C3a, C5a, or IL-17A triggered the expression of inflammatory and angiogenic factors, an effect that was significantly amplified in AhR-knockout cells through increased C3a and IL-8 expression. This heightened inflammatory response was mediated by enhanced NF-κB signaling, associated with defective p65 dephosphorylation by WIP1. These findings reveal a novel regulatory axis where AhR suppresses complement- and IL-17A-driven inflammation, highlighting it as a key hub for regulating blue light-induced retinopathy.

Due to their interesting biological activities, a mannose-binding lectin isolated from Dioclea violacea seeds, known as DvL have attracted considerable attention. In this study, we performed macroscopic, histologic, and immunohistochemical analysis on chicken embryo chorioallantoic membranes (CAM) to investigate the effects of DvL on the angiogenic process. Data showed a potential angiogenic effect of DvL at the highest concentrations tested (50 and 100 μg/mL). This effect was confirmed through increased neovascularization, inflammatory cells, and fibroblasts in histological analysis of the CAM. In addition, the immunohistochemistry of CAM showed that DvL induced secretion of TNF-α and VEGF, important cytokines involved in angiogenesis. Therefore, increased neovascularization may result from a pro-inflammatory response through VEGF and TNF-α secretion. In contrast, the DvL effects on the angiogenic process and the TNF-α and VEGF secretion were significantly reduced by co-incubation with mannose. Thus, protein-carbohydrate interactions between DvL and cell membrane glycans are likely the main events involved in this effect. Therefore, our results demonstrated that DvL is a potent angiogenic agent, suggesting its potential application as a prototype molecule for developing new drugs with healing properties.

The development of new materials for wound care is a critical area, focused on creating dressings with improved properties, such as high absorption, flexibility, and low cost. In this context, natural polymers such as alginate and carboxymethyl cellulose (CMC) emerge as promising choices, given their biodegradability and their ability to promote an ideal healing environment. Concomitantly, lectins with angiogenic potential have been extensively investigated for their ability to modulate cellular responses and induce the formation of new blood vessels. This research aims to incorporate the lectin from Canavalia ensiformis (ConA) into alginate and carboxymethylcellulose (CMC) films to promote blood vessel growth and induce revascularization as a therapeutic approach. Film characterization and physicochemical tests showed efficient lectin/film incorporation, as observed through differential scanning calorimetry (DSC) analysis and Fourier-transform infrared spectroscopy (FTIR). DSC analysis showed that alginate/CMC films with ConA tend to retain less water, volatilizing more easily, with a temperature difference of 94 and 81 °C to 69 and 77 °C films containing ConA. In addition to the significantly prolonged retention capacity of ConA in the film, FTIR data suggest that ConA is anchored in the alginate matrix due to the cross-linked nature of the film chain, with minimal chemical interactions (or chemical bonds). Analysis of hemagglutinating activity and immunohistochemical assays showed an increase in the expression of the angiogenic factors TGF-β and VEGF. These results indicate that the biopolymers used are an effective alternative for wound treatment, pointing to future research into the development of therapeutic biofilms.

Monitoring the quality of water resources is essential to determine environmental impacts and seek sustainable management solutions. In this work, we demonstrated the toxicity of effluents and surface water of an important river in Central Brazil, the Meia Ponte River, using not just physicochemical parameters but also ecotoxicological bioindicators, such as Aliivibrio fischeri, Allium cepa, Lactuca sativa, and Salmonella typhimurium. To complement this data, we analyzed soil toxicity and quality along the river bank using A. fischeri and microbial enzymes. The data was associated with the land use pattern to discuss the environmental impacts caused by the land use and cover in the Cerrado biome. Although most physicochemical parameters were within the values allowed by Brazilian legislation, the A. fischeri bioluminescence inhibition assay indicated sample toxicity mainly in the non-treated effluent and near the river mouth (both water and soil samples). The germination indexes for L. sativa and A. cepa were reduced in most samples. Mutagenicity was observed in a surface water sample of one collection point during the dry season. The current data suggest the toxic potential of the surface water and soil along the Meia Ponte River and the non-treated effluent. The effluent treatment decreased the toxic potential of the samples but did not always eliminate the toxicity. The toxicity of the Meia Ponte River was most observed in urban and agricultural areas. Finally, our work demonstrated the need to monitor the environmental health of the Meia Ponte River basin, also used for public water supply.

Retinal pigment epithelium (RPE) cells, located between the photoreceptors and choroid, play a crucial role in maintaining retinal health and function. They act as immunosuppressive barriers, preventing immune cell infiltration from the choroid. Retinal inflammation contributes to the development of various ocular diseases. The aryl hydrocarbon receptor (AHR) is a well-established ligand-dependent transcription factor that mediates potent anti-inflammatory signals following ligand binding. AHR expression is notably reduced under several conditions that negatively affect the retina. We hypothesized that AHR protein loss may impair RPE cell function, shifting them toward a proinflammatory phenotype. In this study, we investigated the proinflammatory pathways activated by AHR knockout (AHR-KO) and examined associated retinal phenotypic changes in AHR-KO mice. Our findings suggest that AHR deficiency may enhance the activity of αvβ3-integrin, extracellular signal-regulated kinase 1/2, and p65 subunit of nuclear factor kappa B, leading to an upregulation of intercellular adhesion molecule 1 (ICAM1) and promoting monocyte adhesion in vitro. Introducing an AHR-green fluorescent protein into AHR-KO RPE cells or pretreating the cells with pharmacologic inhibitors targeting αvβ3 (cyclo[RGDfk]), focal adhesion kinase (PF573228), phospholipase C (U73122), extracellular signal-regulated kinase 1/2 (U0126), and nuclear factor kappa B (Bay11-7082) prevented ICAM1 induction in AHR-KO RPE cells. These results suggest that the proinflammatory pathway is driven by AHR deficiency. In AHR-KO mice, retinal tissues showed ICAM1 accumulation, microglial activation, and migration, indicating chronic retinal inflammation because of AHR deficiency. These mice also displayed early-onset electroretinogram degeneration. Collectively, our data support the protective role of AHR in maintaining RPE cell physiology and retinal health.

Fluopyram is a fungicide with nematicidal properties widely used in agriculture, found in commercial products for agricultural pest management. Despite its increasing agricultural use, limited information exists on its cytogenotoxic and plant-level impacts. This study evaluated the cytogenotoxic and ecotoxicological effects of a fluopyram-based formulation on non-target organisms, including Salmonella typhimurium (TA98 and TA100 strains), Artemia salina, and seeds of Lactuca sativa (lettuce), Allium cepa (onion), and Cucumis sativus (cucumber). Concentrations ranging from 0.017 to 5.00 mg mL-1 were tested. The pesticide did not induce mutagenic responses in the Salmonella strains tested but demonstrated cytotoxicity at high concentrations (≥1.67 mg mL-1). In A. salina, increasing mortality was observed from 0.210 mg mL-1, with an estimated LC50 of 1.021 mg mL-1. Regarding germination, onion seeds were affected at the highest tested concentration, while root growth in plant species exhibited a hormetic response, with stimulation at low concentrations and inhibition at higher ones. These findings underscore the need for continued environmental monitoring and risk assessment of fluopyram-based formulations, particularly regarding aquatic and plant ecosystems.

Angiogenesis plays a vital role in tumor development, and its inhibition, along with selective cytotoxicity, represents a promising strategy for cancer treatment. Lectins, carbohydrate-binding proteins, have demonstrated dual potential in blocking angiogenesis and selectively targeting tumor cells. This study investigates the antiangiogenic and cytotoxic properties of Vatairea macrocarpa lectin (VML) through the chorioallantoic membrane (CAM) assay and tests on normal VERO cells and tumor cell lines A549, SH-SY5Y, S180, and B16-F10. VML exhibited selective cytotoxicity exclusively against A549 lung carcinoma cells, with an IC50 of 97.21 μg/mL, showing no significant toxicity to other lines. In the CAM assay, VML significantly inhibited neovascularization triggered by A549 cells, reaching 70.38% inhibition at 100 μg/mL. Immunohistochemical analyses confirmed the suppression of angiogenesis by showing decreased expression of VEGF and TGF-β. Histological assessments also revealed reductions in new vessel formation, inflammatory cell infiltration, fibroblast presence, and membrane thickening. These results highlight VML's dual role in inhibiting angiogenesis and exerting selective cytotoxicity, likely due to its specific interaction with tumor-associated carbohydrates. Consequently, VML emerges as a potential candidate for targeted cancer therapy or as a complementary therapeutic agent. Further research is necessary to fully understand the molecular mechanisms underlying its antitumor activity.

Oenothein B (OeB), a dimeric ellagitannin with a macrocyclic structure, is reported to have beneficial effects, including antioxidant, antitumor, antiviral, and antimutagenic effects, on human health. Despite the remarkable properties of OeB, its role in neovascularization process has not yet been evaluated. Thus, this study aimed to evaluate the angiogenic activity of OeB using a chorioallantoic membrane (CAM) assay at different concentrations (6.25, 12.5, and 25 μg/μL), employing digital imaging and histological analysis. Furthermore, to elucidate the mechanisms by which OeB influences angiogenesis, we assessed the levels of vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha (TNF-α) in CAM using immunohistochemical analysis. All concentrations of OeB significantly increased (p < 0.05) the percentage of vascularization as well as the levels of all the angiogenesis-associated parameters evaluated, indicating the pronounced pro-angiogenic activity of OeB. Our results showed that inflammation was one of the most relevant phenomena observed in CAM histology along with angiogenesis. In addition, a significant increase in VEGF and TNF-α levels was observed in all the CAMs compared to the negative control (p < 0.05). We suggest that OeB may induce the presence of inflammatory cells in CAM, leading to increased VEGF and TNF-α levels that result in the induction of angiogenesis. Therefore, OeB presents a favorable profile that could be further explored for the development of drugs for pro-angiogenic and tissue repair therapies.

Pedunculagin (PD) and tellimagrandin-I (TL), isolated from Myrciaria cauliflora seeds and Eucaliptus microcorys leaves, respectively, have attracted great attention owing to their relevant biological activities, such as antitumor, antioxidant, and hepatoprotective activities. This study investigated the angiogenic potential of PD and TL using a chick embryo chorioallantoic membrane (CAM) assay. Using the CAM assay, our results showed that both PD and TL promoted a significant increase in the number and caliber of blood vessels, the thickness of the CAM, and the presence of fibroblasts and inflammatory cells. Moreover, an increase of tumor necrosis factor-α and vascular endothelial growth factor was observed in the CAM treated with PD and TL, indicating the induction of angiogenic factors. Thus, the remarkable profile of PD and TL in inducing angiogenesis opens up new perspectives for their potential utilization in different therapeutic approaches involving neovascularization.

Background MARCKS (myristoylated alanine-rich C kinase substrates) serves as a substrate for protein kinase C, residing in the plasma membrane while acts as an actin filament crosslinking protein. This investigation aims to elucidate phosphorylated MARCKS (p-MARCKS) levels and activity in allergic asthma patients and explore the therapeutic potential of peptide inhibitors targeting p-MARCKS in an acute mouse model of allergic asthma. Methods Immunohistochemistry and histology staining were employed on lung tissue slides to evaluate p-MARCKS expression and allergic asthma symptoms. Airway resistance was measured using invasive whole-body plethysmography. Flow cytometry detected lung dendritic cell migration, and migration/maturation assays were conducted on isolated murine bone marrow-derived dendritic cells (BM-DCs). Results Elevated p-MARCKS expression was observed in both human asthmatic tissues and animal models immunized with ovalbumin or Alternaria alternata. Remarkably, asthmatic individuals showed elevated high p-MARCKS expression in lung tissues. Intraperitoneal injection of the peptide MPS, targeting the MARCKS phosphorylation site domain, before allergen challenged, effectively suppressed MARCKS phosphorylation in murine lung tissues. MPS inhibited both in vivo and in vitro migration and maturation of dendritic cells (BM-DCs) and reduced Th2-related lymphocyte activation in bronchoalveolar lavage fluid (BALF). MPS pretreatment additionally suppressed all symptoms associated with allergic airway asthma, including a reduction in inflammatory cell influx, airway mucous cell metaplasia, and airway hyperreactivity. Conclusion These findings suggest that phosphorylated MARCKS occurs in asthmatic lung tissue, and the inhibition of MARCKS phosphorylation by the MPS peptide reduces dendritic cell migration and Th2-related lymphocytes in the lungs in a murine model of acute asthma.

Dioclea violacea seed mannose-binding lectin (DvL) has attracted considerable attention because of its interesting biological activities, including antitumor, antioxidant, and anti-inflammatory activities. This study evaluated the cytotoxic effect of DvL on tumor and normal cells using the mitochondrial activity reduction (MTT) assay, the carcinogenic and anti-carcinogenic activity by the epithelial tumor test (ETT) in Drosophila melanogaster, and the anti-angiogenic effect by the chick embryo chorioallantoic membrane (CAM) assay. Data demonstrated that DvL promoted strong selective cytotoxicity against tumor cell lines, especially A549 and S180 cells, whereas normal cell lines were weakly affected. Furthermore, DvL did not promote carcinogenesis in D. melanogaster at any concentration tested, but modulated DXRinduced carcinogenesis at the highest concentrations tested. In the CAM and immunohistochemical assays, DvL inhibited sarcoma 180-induced angiogenesis and promoted the reduction of VEGF and TGF-b levels at all concentrations tested. Therefore, our results demonstrated that DvL is a potent anticancer, anti-angiogenic, and selective cytotoxic agent for tumor cells, suggesting its potential application as a prototype molecule for the development of new drugs with chemoprotective and/or antitumor effects. (c) 2024 Published by Elsevier B.V.

Diabetic retinopathy (DR) is a severe consequence of long-term diabetes mellitus and may lead to vision loss. Retinal pigment epithelial (RPE) cells are a diverse group of retinal cells with varied metabolic and functional roles. In hypoxic conditions, RPE cells have been shown to produce angiogenic factors, such as vascular endothelial growth factor (VEGF), which is regulated by hypoxia-inducible factor 1-alpha (HIF1A). VEGF plays a crucial role in angiogenesis in DR. In the present study, we investigated whether azatyrosine-phenylbutyric hydroxamide (AZP) has therapeutic effect on DR therapy. In this study, we treated high glucose-activated human retinal pigment epithelial cells (ARPE-19) with and without AZP. The effector proteins were evaluated using western blotting. In the in vivo study, AZP was administered to the db/db mice as a DR animal model. Moreover, invasive imaging techniques such as optical coherence tomography (OCT), fundus photography, and fundus fluorescein angiography (FFA) were performed on the mice to assess DR progression. We found that treatment of AZP for 12 weeks reversed increasing DR retinal alterations in db/db mice, decreasing vascular density, retinal blood perfusion, retinal thickness, decreasing DR lesion, lipofuscin accumulation, HIF1A, VEGF, and inflammation factor expression. In addition, AZP treatment could activate the aryl hydrocarbon receptor AHR and reverse the high-glucose-induced HIF1A and VEGF in ARPE-19 cells and db/db mice. In conclusion, AZP activated AHR while inhibiting HIF1A and VEGF. This study indicates that AZP may be a promising therapeutic agent for treating DR.

Oenothein B (OeB) is a dimeric ellagitannin with potent antioxidative, antitumor, immunomodulatory, and anti-inflammatory properties. Despite the promising activities of OeB, studies examining the genotoxic or protective effects of this ellagitannin on DNA are scarce. Therefore, to further comprehensively elucidate the chemopreventive profile of OeB, the aim of this study was to evaluate the mutagenic and antimutagenic actions of OeB using Salmonella typhimurium strains with the Ames test. The micronucleus (MN) test and comet assay were used to assess the anticytotoxic and antigenotoxic effects of OeB on mouse bone marrow cells following differing treatments (pre-, co-, and post-treatment) in response to cyclophosphamide (CPA)-induced DNA damage. In addition, histopathological analyses were performed to assess liver and kidney tissues of Swiss Webster treated mice. Our results did not detect mutagenic or antimutagenic activity attributed to OeB at any concentration in the Ames test. Regarding the MN test, data showed that this ellagitannin exerted antigenotoxic and anticytotoxic effects against CPA-induced DNA damage under all treatment conditions. However, no anticytotoxic action was observed in MN test after pre-treatment with the highest doses of OeB. In addition, OeB demonstrated antigenotoxic effects in the comet assay for all treatments. Histopathological analyses indicated that OeB attenuated the toxic effects of CPA in mouse liver and kidneys. These findings suggest that OeB exerted a chemoprotective effect following pre- and co-treatments and a DNA repair action in post-treatment experiments. Our findings indicate that OeB protects DNA against CPA-induced damaging agents and induces post-damage DNA repair.

Tellimagrandin-I (TL) and camptothin A (CA) are ellagitannins widely found in diverse plant species. Numerous studies demonstrated their significant biological activities, which include antitumor, antioxidant, and hepatoprotective properties. Despite this protective profile, the effects of TL and CA on DNA have not been comprehensively investigated. Thus, the aim of this study was to determine the mutagenic and antimutagenic effects attributed to TL and CA exposure on Salmonella enterica serovar Typhimurium strains using the Ames test. In addition, the cytotoxic and genotoxic effects were examined on human lymphocytes, employing both trypan blue exclusion and CometChip assay. The antigenotoxic effect was determined following TL and CA exposure in the presence of co-treatment with doxorubicin (DXR). Our results from the Ames test indicated that TL or CA did not display marked mutagenic activity. However, TL or CA demonstrated an ability to protect DNA against the damaging effects of the mutagens 4-nitroquinoline-1-oxide and sodium azide, thereby exhibiting antimutagenic properties. In relation to human lymphocytes, TL or CA did not induce significant cytotoxic or genotoxic actions on these cells. Further, these ellagitannins exhibited an ability to protect DNA from damage induced by DOX during co-treatment, indicating their potential beneficial usefulness as antigenotoxic agents. In conclusion, the protective effects of TL or CA against mutagens, coupled with their absence of genotoxic and cytotoxic effects on human lymphocytes, emphasize their potential therapeutic value in chemopreventive strategies.

Vernonanthura polyanthes (Spreng.) A.J. Vega & Dematt. (syn.: Vernonia polyanthes Less) is popularly known as “assa-peixe” and its leaves are used in folk medicine mainly to treat respiratory diseases. In this study, we evaluated the cytogenotoxic and anticytogenotoxic potential of the V. polyanthes leaf aqueous extract (VpLAE) and its n-butanol fraction (n-BF) in the presence or absence of doxorubicin (DXR) (pre-, co-, and post-treatments) on a murine model for 24 h or 120 h. The micronucleus test (MN) and the comet assay were used to assess the cytogenotoxic and anticytogenotoxic potential of VpLAE and n-BF (250, 500, and 1000 mg/kg) administered via gavage to Swiss Webster mice. The chemical profiles of VpLAE and n-BF were assessed by liquid chromatography coupled to mass spectrometry, and their metabolites were putatively identified. Lastly, the possible biological activities related to the (anti) cytogenotoxicity of the compounds were predicted using the PASS online webserver. The in vivo results showed that different doses of VpLAE and n-BF did not present cytotoxic activity; however, the MN test revealed a slight mutagenic activity for the 24 h treatments. Moderate genotoxic effects were demonstrated for all treatments in the comet assay. Regarding anticytotoxicity and antimutagenicity, VpLAE and n-BF presented a high cytoprotective potential against DXR toxic effects. In the co-treatment, VpLAE reduced the DXR genotoxicity by ~27%, and n-BF did not demonstrate antigenotoxic potential. In contrast, an antigenotoxic effect was observed for both VpLAE and n-BF in the pre- and post-treatments, reducing DXR genotoxicity by ~41% and ~47%, respectively. Chemical analysis of VpLAE and n-BF showed the presence of eight phenolic compounds, including seven chlorogenic acids and a flavonoid. The PASS online tool predicted antimutagenic, anticancer, antineoplastic, chemoprotective, antioxidant, and radical scavenging activities for all constituents identified in VpLAE and n-BF. V. polyanthes leaves presented a protective effect against DXR cytogenotoxicity. In general, VpLAE and n-BF showed a greater antigenotoxic potential in the pre- and post-treatments. The metabolites putatively identified in VpLAE and n-BF exhibited antioxidant and chemoprotective potential according to computational prediction analysis. Altogether, our results highlight the potential application of V. polyanthes to protect against toxic manifestations induced by DXR.

Cerrado has many compounds that have been used as biopesticides, herbicides, medicines, and others due to their highly toxic potential. Thus, this review aims to present information about the toxicity of Cerrado plants. For this purpose, a review was performed using PubMed, Science Direct, and Web Of Science databases. After applying exclusion criteria, 187 articles published in the last 20 years were selected and analyzed. Detailed information about the extract preparation, part of the plant used, dose/concentration tested, model system, and employed assay was provided for different toxic activities described in the literature, namely cytotoxic, genotoxic, mutagenic, antibacterial, antifungal, antiviral, insecticidal, antiparasitic, and molluscicidal activities. In addition, the steps to execute research on plant toxicity and the more common methods employed were discussed. This review synthesized and organized the available research on the toxic effects of Cerrado plants, which could contribute to the future design of new environmentally safe products.

AIMS:Articulatin (AT), purified from the Chinese mistletoe (Viscum articulatum), belongs to the family of type II ribosome-inactivating proteins (RIPs) that contain two subunits, the A and B chains. The B chain of AT is believed to function by means of interacting with the galactose moiety of glycoproteins or glycolipids on the cell membrane and is internalized into cells through endocytosis. In the study, we aim to investigate the immunomodulatory effects of recombinant articulatin B chain (rATB) on mouse bone marrow-derived dendritic cells (BM-DCs). MAIN METHODS:Detection of surface markers expression on BM-DCs by flow cytometry. Analysis of RNA and protein expression by RNAseq and Western blotting assays. Assessment of the adaptive immune responses using an in vivo mouse model. KEY FINDING:Our study presents novel results showing the activation of mouse BM-DCs by rATB, which leads to the induction of CD80, CD86, and MHC II expression as well as primed type I CD4+ T cell differentiation and CD8+ T cell activation. RNAseq and Western blotting assays revealed rATB-induced BM-DC activation to be dependent on the MAPK and NF-κB signaling pathways. In a mouse model, rATB was observed to have adjuvant effects that induced an antigen-specific Th1 immune response. SIGNIFICANCE:Based on in vitro and in vivo assays, this study shows rATB acting as a potential adjuvant that induces BM-DC activation and antigen-specific Th1 related immune response. rATB might have potential applicability in the development of vaccines against pathogens and tumors.

Lactose-binding lectin from Vatairea macrocarpa seeds (VML) has attracted great attention due to its interesting biological activities, such as pro-inflammatory effects and macrophage activation. This study evaluated the cytotoxicity and genotoxicity/antigenotoxicity of VML in human lymphocytes using the CometChip assay, and angiogenic activity by the chick embryo chorioallantoic membrane (CAM) assay. In genotoxicity, lymphocytes were treated with different concentrations of VML (0.5, 2 and 8 μM). In antigenotoxicity, lymphocytes were treated with the same concentrations of VML concomitant doxorubicin (90 μM DXR). To evaluate angiogenesis, all CAM were treated with different concentrations of VML (0.5, 2 and 8 μM) alone or co-treated with lactose (0.1 M). Furthermore, the levels of vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha (TNF-α) in CAM were assessed by immunohistochemistry. The results showed that VML was cytotoxic to lymphocytes, genotoxic at the highest concentration (8 μM) and antigenotoxic at low concentrations (0.5, and 2 μM). Regarding the CAM assay and immunohistochemistry, VML was angiogenic and significantly increased VEGF and TNF-α levels. In contrast, co-treatment with lactose significantly reduced the angiogenic effect and VEGF levels. We propose that protein-carbohydrate interactions between VML and glycans in the cell membrane are probably the major events involved in these activities. It seems likely that VML elicits a pro-inflammatory response through VEGF and TNF-α expression, resulting in increased vascularization at the site of inflammation. Therefore, our results show novel information on the effects of VML on DNA, as well as provide data regarded the neovascularization process involving this lectin.