RESUMEN
Abstract The composition and pharmacological properties of Lippia alba (Mill.) (L. alba) (Verbenaceae) flower and leaf essential oils (EO) were determined in this study. The major constituents in the flower EO were geranial (49.83%) and neral (32.75%), and in the leaf EO were geranial (38.06%), neral (31.02%), and limonene (18.03%). Flower EO inhibited thrombolysis induced by Bothrops moojeni (B. moojeni) and Lachesis muta muta (L. muta muta) venoms (0.05-1.2 µL mL-1). When tested against L. muta muta venom, the protective effect was smaller in both EO. The EOs prolonged the clotting time induced by L. muta muta venom and a procoagulant effect was observed on B. moojeni. In the comet assay, the flower EO presented anti-genotoxic action (damage frequency of only 11.6 - 34.9%) against the L. muta muta venom. The positive control (Doxorubicin) and the venom alone presented a damage frequency of 80.3% and 70.7%, respectively. The flower EO protected DNA from damage induced by L. muta muta venom. L. alba leaf and flower EOs presented anti-genotoxic action
Asunto(s)
Productos Biológicos/análisis , Aceites Volátiles/análisis , Lippia/efectos adversos , Hojas de la Planta/clasificación , Ensayo Cometa/instrumentación , Flores/clasificación , Venenos Elapídicos/farmacología , Inhibidores Enzimáticos/administración & dosificación , HemostasisRESUMEN
Induratia spp. fungi have been poorly evaluated for their non-volatile secondary metabolites. In the present work, we evaluated the effects of non-volatile secondary metabolites released into the culture medium by Induratia spp. upon toxic alterations induced by Bothrops spp. venoms. B. atrox venom phospholipase was inhibited by Induratia spp. around 12 and 16%. The extracts of the two strains inhibited 12-25% of the hemolysis induced by B.moojeni venom. Thrombolysis was inhibited by 30-60% by the compounds present in both extracts. The coagulation induced by B. moojeni venom was prolonged by 26-41 s by the action of the extracts of I. coffeana. The fungal extracts did not exert any cytotoxic effect, nor did they induce any alteration in the other evaluated substrates show the potential use of non-volatile metabolites produced by the fungi evaluated as enzyme modulators, especially for proteases with a fundamental role in human hemostasis.
Asunto(s)
Endopeptidasas , Hemostasis , Péptido Hidrolasas , Xylariales/química , Animales , Bothrops , Muerte Celular , Humanos , Venenos de SerpienteRESUMEN
The research and development of alternative treatments for snakebites (e.g., medicinal plants) is necessary due to the high costs of the existing ones. The effects of the aqueous extracts from Jacaranda decurrens leaves, roots, and xylopodium were analyzed upon the venom-induced (Bothrops spp. and Crotalus spp.) systemic and local toxicity. The extracts were able to partially inhibit the phospholipase activity of the venoms from Bothrops jararacussu and Crotalus durissus terrificus. The myotoxic, edema-inducing, coagulant, and hemorrhagic activities were also inhibited. The SDS-PAGE showed that the venom proteins were intact after their incubation with the extracts. This suggests that the possible mechanism of inhibition is not related to the degradation of the protein but rather to their binding to specific sites of the enzymes. The extracts significantly prolonged the survival time of animals in the lethality assay performed with Crotalus durissus terrificus venom and its toxin (crotoxin). The anti-ophidic activity of medicinal plants may aid in the management of snakebites in distant locations by reducing the victims local effects and time to heal.
Asunto(s)
Bignoniaceae/toxicidad , Plantas Medicinales/toxicidad , Técnicas In Vitro , Venenos de CrotálidosRESUMEN
In the present work, ethyl acetate extracts, consisting of non-volatile compounds, from the culture of endophytic fungi isolated from coffee plants, Induratia coffeana and Induratia yucatanensis, were prospected in enzyme modulation tests that act in human hemostasis. Dry extracts of the fungi were diluted in dimethyl sulfoxide p.a. 99.9% (DMSO), and then tested. Bothrops atrox venom was used as an enzyme source and tool to induce the activities. Prior to the evaluation of the activities, incubations of the extracts with the venom were performed in the proportions 1: 0.01, 1: 0.25, 1: 0.5, and 1: 1 (venom: extract; mass: mass). The extracts of all fungi promoted a significant increase in the clotting time induced by the venom, which was even longer when the extracts were previously incubated with the citrated plasma. The activity of phospholipases A2 did not significantly change when evaluated in the presence of fungal extracts. However, the evaluated extracts inhibited proteases by 73% and 30% in the thrombolytic and caseinolytic tests, respectively. In addition, the extracts did not induce cytotoxicity on human erythrocytes when evaluated in the absence of the venom. Thus, it is possible to suggest the presence of specific interactions between molecules present in extracts of Induratia spp. and venom proteases, highlighting non-volatile metabolites as promising sources of compounds of medical and scientific interest.
Asunto(s)
Extractos Vegetales , Xylariales , Humanos , Fosfolipasas A2 , Extractos Vegetales/farmacologíaRESUMEN
The protective action of caffeic (CA) and syringic (SA) acids on the genotoxicity exercised by snake venoms was investigated in this study. Molecular interactions between phenolic acids and the enzyme succinate dehydrogenase were also explored. In the electrophoresis assay, SA did not inhibit the genotoxicity induced by the venom. However, CA partially inhibited DNA degradation. In the comet assay, SA and CA exerted an inhibitory effect on the venom-induced fragmentation. Succinate dehydrogenase presented, in computational analyzes, favorable energies to the molecular bond to both the malonic acid and the phenolic compounds evaluated. In the enzymatic activity assays, SA inhibited succinate dehydrogenase and interfered in the interaction of malonic acid. Meanwhile, CA potentiated the inhibition exerted by the malonic acid. The results suggest transient interactions between toxins present in venoms and phenolic acids, mainly by hydrogen interactions, which corroborate with the data from previous works.
Asunto(s)
ADN/efectos de los fármacos , Hidroxibenzoatos/farmacología , Mitocondrias/efectos de los fármacos , Succinato Deshidrogenasa/metabolismo , Adulto , Ensayo Cometa , Daño del ADN , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
Naja spp. venom is a natural source of active compounds with therapeutic application potential. Phospholipase A2 (PLA2) is abundant in the venom of Naja spp. and can perform neurotoxicity, cytotoxicity, cardiotoxicity, and hematological disorders. The PLA2s from Naja spp. venoms are Asp 49 isoenzymes with the exception of PLA2 Cys 49 from Naja sagittifera. When looking at the functional aspects, the neurotoxicity occurs by PLA2 called ß-toxins that have affinity for phosphatidylcholine in nerve endings and synaptosomes membranes, and by α-toxins that block the nicotinic acetylcholine receptors in the neuromuscular junctions. In addition, these neurotoxins may inhibit K+ and Ca++ channels or even interfere with the Na+/K+/ATPase enzyme. The disturbance in the membrane fluidity also results in inhibition of the release of acetylcholine. The PLA2 can act as anticoagulants or procoagulant. The cytotoxicity exerted by PLA2s result from changes in the cardiomyocyte membranes, triggering cardiac failure and hemolysis. The antibacterial activity, however, is the result of alterations that decrease the stability of the lipid bilayer. Thus, the understanding of the structural and functional aspects of PLA2s can contribute to studies on the toxic and therapeutic mechanisms involved in the envenomation by Naja spp. and in the treatment of pathologies.
Asunto(s)
Proteínas Neurotóxicas de Elápidos , Naja , Unión Neuromuscular/metabolismo , Fosfolipasas A2 , Sinaptosomas/metabolismo , Animales , Proteínas Neurotóxicas de Elápidos/química , Proteínas Neurotóxicas de Elápidos/uso terapéutico , Unión Neuromuscular/patología , Fosfatidilcolinas/química , Fosfatidilcolinas/metabolismo , Fosfolipasas A2/química , Fosfolipasas A2/uso terapéutico , Relación Estructura-Actividad , Sinaptosomas/patologíaRESUMEN
Spent pot liner (SPL) is a toxic solid waste generated in the aluminum mining and processing industry. SPL is considered as an environmental pollution agent when is dumped on environment. Thus, it is important to access its toxicological risk for the exposed organisms. The comet assay and micronucleus test are efficient tests to detect genotoxic/mutagenic compounds by DNA damage observation. Therefore, in the present study, the genotoxic potential of SPL was evaluated through the micronucleus and comet assay on human leukocytes. After ethics committee approval (COEP-UFLA n°. CAAE 11355312.8.0000.5060), blood aliquots collected from healthy volunteers were exposed to increasing concentrations of SPL (from 0.1 to 80 g L-1). All SPL treatments, including the lowest concentration applied (0.1 g L-1), significantly increased the micronucleus frequency. The frequency of DNA damage was determined by visual scores (from 0 to 4) and the results were expressed on percentage of damage and arbitrary units (AU). CaCl2 (0.01 M) was applied as negative control (NC) and doxorubicin (10 µg mL-1) as positive control (PC). It was observed a dose-dependency between SPL treatments: as SPL concentration for cell incubation increases, the frequency of damage on DNA also increases. Cells incubated on the NC presented nucleoids class 0 to 2, while those exposed to SPL presents nucleoids class 0 to 4. SPL-incubated cells increasing significantly the frequency of nucleoids class 4. For the PC, the UA of damage was 267.74, which is lower than the one observed for the treatments with high doses of SPL (40-287.40 g L-1 and 80-315.30 g L-1). Thus, it was demonstrated that the SPL is a genotoxic agent that induces DNA damage on exposed organisms.
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Aluminio/toxicidad , Núcleo Celular/efectos de los fármacos , Leucocitos/efectos de los fármacos , Mutágenos/toxicidad , Adulto , Ensayo Cometa , Daño del ADN , Humanos , Pruebas de Micronúcleos , Minería , MutagénesisRESUMEN
Disintegrins are non-enzymatic proteins that interfere on cell-cell interactions and signal transduction, contributing to the toxicity of snake venoms and play an essential role in envenomations. Most of their pharmacological and toxic effects are the result of the interaction of these molecules with cell surface ligands, which has been widely described and studied. These proteins may act on platelets, leading to hemorrhage, and may also induce apoptosis and cytotoxicity, which highlights a high pharmacological potential for the development of thrombolytic and antitumor agents. Additionally, these molecules interfere with the functions of integrins by altering various cellular processes such as migration, adhesion and proliferation. This review gathers information on functional characteristics of disintegrins isolated from snake venoms, emphasizing a comprehensive view of the possibility of direct use of these molecules in the development of new drugs, or even indirectly as structural models.
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Desintegrinas/farmacología , Integrinas/metabolismo , Venenos de Serpiente/metabolismo , Animales , Plaquetas/citología , Plaquetas/efectos de los fármacos , Adhesión Celular/efectos de los fármacos , Comunicación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Humanos , Transducción de Señal/efectos de los fármacosRESUMEN
Prophylactic antibiotics and growth promoters have been substituted, mainly for livestock, by immunomodulators and intestinal health promoters - such as ß-D-glucans and glutamine. The aim of this study was to verify the beneficial effects of ß-D-glucans and glutamine against Cytarabine/Ara-C, evaluating the DNA damage in leukocytes, the leukogram, and the mitotic index of intestinal crypts cells. Balb/C mice received treatment with ß-D-glucan (80â¯mg/Kg), glutamine (150â¯mg/Kg), or both, for 21â¯days. On the last two days of this period, Ara-C was administered (1.8â¯mg/animal) by intraperitoneal injection every 12â¯h. The animals submitted to the treatment with Ara-C presented the highest genotoxic index, a significant leukopenia, and a decrease in the mitotic index of the intestinal crypts cells. Treatment with ß-D-glucan protected the leukocytes against DNA fragmentation induced by Ara-C. Glutamine alone promoted maintenance of the mitotic index and, in association with ß-Dglucan, reduced leukopenia. Thus, the use of ß-D-glucan and glutamine proved to be beneficial to intestinal tropism. This can happen once the damage to the genetic material, prevented by the treatments with ß-D-glucan and glutamine, can result in genotoxicity. Not only this, but it might be capable of turning into a mutagenesis, with consequential physiopathological alterations.
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Daño del ADN/efectos de los fármacos , Fragmentación del ADN/efectos de los fármacos , Inestabilidad Genómica/efectos de los fármacos , beta-Glucanos/administración & dosificación , Animales , Citarabina/toxicidad , Glutamina/administración & dosificación , Inyecciones Intraperitoneales , Leucocitos/efectos de los fármacos , Ratones , Ratones Endogámicos BALB CRESUMEN
BACKGROUND: Essential oils are complex mixtures of low molecular weight compounds extracted from plants. Their main constituents are terpenes and phenylpropanoids, which are responsible for their biological and pharmaceutical properties, such as insecticidal, parasiticidal, antimicrobial, antioxidant, anti-inflammatory, analgesic, antinociceptive, anticarcinogenic, and antitumor properties. Cancer is a complex genetic disease considered as a serious public health problem worldwide, accounting for more than 8 million deaths annually. OBJECTIVE: The activities of prevention and treatment of different types of cancer and the medicinal potential of essential oils are addressed in this review. CONCLUSION: Several studies have demonstrated anti-carcinogenic and antitumor activity for many essential oils obtained from various plant species. They may be used as a substitution to or in addition to conventional anti-cancer therapy. Although many studies report possible mechanisms of action for essential oils compounds, more studies are necessary in order to apply them safely and appropriately in cancer therapy.