RESUMEN
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.
Asunto(s)
Factor de Necrosis Tumoral alfa , Factor A de Crecimiento Endotelial Vascular , Animales , Embrión de Pollo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Angiogénesis , Neovascularización Fisiológica , Factores de Crecimiento Endotelial Vascular , Membrana Corioalantoides/irrigación sanguínea , InflamaciónRESUMEN
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.
Asunto(s)
Antimutagênicos , Salmonella enterica , Humanos , Salmonella typhimurium/genética , Salmonella enterica/genética , Taninos Hidrolizables/farmacología , Serogrupo , Pruebas de Mutagenicidad , Mutágenos/toxicidad , Antimutagênicos/farmacología , Extractos Vegetales/farmacología , Carcinógenos/farmacología , ADN/farmacología , LinfocitosRESUMEN
Chalcones and sulfonamides are well-known chemical groups associated with several biological activities such as antibiotic, anti-inflammatory, and antitumor activities. Over the past few decades, a series of sulfonamide-chalcone hybrids have been synthesized and assessed to develop compounds with interesting biological properties for application in disease therapy. In the present study, a new sulfonamide-chalcone hybrid µ - (2,5-dichloro-N-{4-[(3E)-4-(3-nitrophenyl) buta-1,3-dien-2-yl] phenyl} benzene sulfonamide), or simply CL185, was synthesized, and its angiogenic activity was assessed using the chick embryo chorioallantoic membrane (CAM) assay at different concentrations (12.5, 25, and 50 µg/µL). To further investigate the role of CL185 in the angiogenic process, we evaluated the levels of vascular endothelial growth factor (VEGF) in all treated CAMs. The results showed that all concentrations of CL185 significantly increased tissue vascularization (p < 0.05) as well as the parameters associated with angiogenesis, in which inflammation was the most marked phenomenon observed. In all CAMs treated with CL185, VEGF levels were significantly higher than those in the negative control (p < 0.05), and at the highest concentration, VEGF levels were even higher than in the positive control (p < 0.05). The pronounced angiogenic activity displayed by CL185 may be related to the increase in VEGF levels that were stimulated by inflammatory processes observed in our study. Therefore, CL185 presents a favorable profile for the development of drugs that can be used in pro-angiogenic and tissue repair therapies.
Asunto(s)
Inductores de la Angiogénesis/farmacología , Chalconas/farmacología , Membrana Corioalantoides/irrigación sanguínea , Inflamación/metabolismo , Neovascularización Fisiológica/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Inductores de la Angiogénesis/toxicidad , Animales , Chalconas/toxicidad , Embrión de Pollo , Inflamación/inducido químicamente , Regulación hacia ArribaRESUMEN
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.
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Antiinfecciosos , Plantas Medicinales , Antifúngicos , Brasil , Medicina Tradicional , Extractos Vegetales/efectos adversos , Plantas Medicinales/efectos adversosRESUMEN
Azathioprine (AZA) is the main drug used in immunomodulatory therapy in post-transplant patients or with autoimmune diseases. However, no study has evaluated the AZA angiogenic response. Therefore, this study investigated the effects of AZA on the angiogenic process through macroscopic, histological, and immunohistochemical analyses in chick embryo chorioallantoic membrane (CAM). Our results showed potent anti-angiogenic activity of AZA at the higher concentrations tested in the CAM assay. The histological analysis of CAM confirmed this effect, since AZA induced a significant reduction in all parameters evaluated. In addition, immunohistochemical evaluation of CAM revealed that AZA decreased TGF-ß and VEGF levels, important cytokines involved in the angiogenic process. Therefore, the AZA anti-angiogenic effect identified in our study provides new information for the possible application of this drug in anticancer treatment.
Asunto(s)
Inhibidores de la Angiogénesis/farmacología , Azatioprina/farmacología , Vasos Sanguíneos/efectos de los fármacos , Membrana Corioalantoides/irrigación sanguínea , Neovascularización Fisiológica/efectos de los fármacos , Animales , Vasos Sanguíneos/metabolismo , Embrión de Pollo , Factor de Crecimiento Transformador beta/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
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 DXR-induced 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-ß 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.
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Dioclea , Drosophila melanogaster , Neovascularización Patológica , Animales , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/metabolismo , Humanos , Dioclea/química , Embrión de Pollo , Drosophila melanogaster/efectos de los fármacos , Carcinogénesis/efectos de los fármacos , Inhibidores de la Angiogénesis/farmacología , Membrana Corioalantoides/efectos de los fármacos , Membrana Corioalantoides/irrigación sanguínea , Lectinas de Plantas/farmacología , Células A549 , Línea Celular Tumoral , Ratones , AngiogénesisRESUMEN
Prednisone (PD) is one of the most commonly used corticosteroids in immunosuppressive therapy for patients with autoimmune diseases and transplants. Chronic use of corticosteroids is associated with several side effects and an increase in neoplasia. Since genotoxic effects are associated with an increased risk of cancer development, this study evaluated the genotoxic and cytotoxic activities of PD using the SMART/wing assay in Drosophila melanogaster and the micronucleus test and comet assay in mouse bone marrow cells. Further, the toxic effects of PD on mouse organ tissues were assessed using histopathological analyses. In the SMART/wing assay, PD showed a significant genotoxic activity at all concentrations tested (0.375, 0.75, 1.5, and 2.0 mg/mL) compared to the negative control (p < 0.05). The micronucleus test and comet assay also showed an elevated genotoxicity of PD at all treatment conditions (24, 48, and 120 h with doses ranging from 0.5 to 1.5 mg/kg) compared to the negative control (p < 0.05). The histopathological analyses did not show toxicity of PD in mouse cells and tissues. Therefore, our results demonstrate that PD is a potent genotoxic immunosuppressant in mice and D. melanogaster cells. Somatic recombination was the primary contributor (46%-82%) to the induced genotoxicity observed in the SMART test.
Asunto(s)
Daño del ADN/efectos de los fármacos , Prednisona/efectos adversos , Animales , Animales Modificados Genéticamente , Animales no Consanguíneos , Ensayo Cometa , Drosophila melanogaster , Femenino , Masculino , Ratones , Pruebas de Micronúcleos , Pruebas de Mutagenicidad/métodos , Mutágenos/toxicidadRESUMEN
BACKGROUND: Gemin D (GD) is an ellagitannin found in several plant species rich in phenolic compounds. Its many beneficial properties include antioxidant and antitumoral. OBJECTIVE: The present study assessed the genotoxicity, cytotoxicity, antigenotoxicity, and anticytotoxicity of GD by in vitro and in vivo assays. METHOD: The Ames mutagenicity assay in Salmonella typhimurium, Micronucleus and Comet tests in mice were used to evaluate the biological activities mentioned above. To assess the GD's protective effects against DNA damage induced by different mutagens we performed co-, pre- and/or post-treatment in these assays. RESULTS: There was no genotoxic effect of GD via Ames and Micronucleus tests, but in the Comet assay the highest dose induced DNA damage. This same highest dose presented a significant cytotoxicity in mice. In the antigenotoxicity, GD protected DNA against the action of 4-nitroquinoline-1-oxide and sodium azide by Ames test, and also against the harmful action of cyclophosphamide in pre- and co-treatment by Micronucleus and Comet tests, but it did not protect DNA in post-treatment. Regarding to anticytotoxicity, GD provoked an anticytotoxic effect only during pre-treatment. CONCLUSION: Therefore, GD showed relevant antigenotoxic, anticytotoxic and cytotoxic effects, which indicate that it may be a probable candidate for chemoprevention or for the development of new cancer therapies.