RESUMEN
Iprodione is a pesticide that belongs to the dicarboximide fungicide family. This pesticide was designed to combat various agronomical pests; however, its use has been restricted due to its environmental toxicity and risks to human health. In this study, we explored the proteomic changes in the Pseudomonas sp. C9 strain when exposed to iprodione, to gain insights into the affected metabolic pathways and enzymes involved in iprodione tolerance and biodegradation processes. As a result, we identified 1472 differentially expressed proteins in response to iprodione exposure, with 978 proteins showing significant variations. We observed that the C9 strain upregulated the expression of efflux pumps, enhancing its tolerance to iprodione and other harmful compounds. Peptidoglycan-binding proteins LysM, glutamine amidotransferase, and protein Ddl were similarly upregulated, indicating their potential role in altering and preserving bacterial cell wall structure, thereby enhancing tolerance. We also observed the presence of hydrolases and amidohydrolases, essential enzymes for iprodione biodegradation. Furthermore, the exclusive identification of ABC transporters and multidrug efflux complexes among proteins present only during iprodione exposure suggests potential counteraction against the inhibitory effects of iprodione on downregulated proteins. These findings provide new insights into iprodione tolerance and biodegradation by the Pseudomonas sp. C9 strain.
Asunto(s)
Proteínas Bacterianas , Hidantoínas , Proteoma , Pseudomonas , Pseudomonas/metabolismo , Pseudomonas/efectos de los fármacos , Pseudomonas/genética , Proteoma/metabolismo , Hidantoínas/farmacología , Hidantoínas/metabolismo , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Proteómica/métodos , Biodegradación Ambiental , Fungicidas Industriales/farmacología , Fungicidas Industriales/toxicidad , Plaguicidas/toxicidad , Plaguicidas/farmacología , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/farmacología , Aminoimidazol Carboxamida/metabolismo , Regulación Bacteriana de la Expresión Génica/efectos de los fármacosRESUMEN
Leptin is a cytokine, produced mainly by mature adipocytes, that regulates the central nervous system, mainly to suppress appetite and stimulate energy expenditure. Leptin also regulates the immune response by controlling activation of immunomodulatory cells, including eosinophils. While emerging as immune regulatory cells with roles in adipose tissue homeostasis, eosinophils have a well-established ability to synthesize pro-inflammatory molecules such as lipid mediators, a key event in several inflammatory pathologies. Here, we investigated the impact and mechanisms involved in leptin-driven activation of eicosanoid-synthesizing machinery within eosinophils. Direct in vitro activation of human or mouse eosinophils with leptin elicited synthesis of lipoxygenase as well as cyclooxygenase products. Displaying selectivity, leptin triggered synthesis of LTC4 and PGD2, but not PGE2, in parallel to dose-dependent induction of lipid body/lipid droplets biogenesis. While dependent on PI3K activation, leptin-driven eosinophil activation was also sensitive to pertussis toxin, indicating the involvement of G-protein coupled receptors on leptin effects. Leptin-induced lipid body-driven LTC4 synthesis appeared to be mediated through autocrine activation of G-coupled CCR3 receptors by eosinophil-derived CCL5, inasmuch as leptin was able to trigger rapid CCL5 secretion, and neutralizing anti-RANTES or anti-CCR3 antibodies blocked lipid body assembly and LTC4 synthesis induced by leptin. Remarkably, autocrine activation of PGD2 G-coupled receptors DP1 and DP2 also contributes to leptin-elicited lipid body-driven LTC4 synthesis by eosinophils in a PGD2-dependent fashion. Blockade of leptin-induced PGD2 autocrine/paracrine activity by a specific synthesis inhibitor or DP1 and DP2 receptor antagonists, inhibited both lipid body biogenesis and LTC4 synthesis induced by leptin stimulation within eosinophils. In addition, CCL5-driven CCR3 activation appears to precede PGD2 receptor activation within eosinophils, since neutralizing anti-CCL5 or anti-CCR3 antibodies inhibited leptin-induced PGD2 secretion, while it failed to alter PGD2-induced LTC4 synthesis. Altogether, sequential activation of CCR3 and then PGD2 receptors by autocrine ligands in response to leptin stimulation of eosinophils culminates with eosinophil activation, characterized here by assembly of lipidic cytoplasmic platforms synthesis and secretion of the pleiotropic lipid mediators, PGD2, and LTC4.
Asunto(s)
Eosinófilos/inmunología , Leptina/metabolismo , Leucotrieno C4/biosíntesis , Receptores CCR3/metabolismo , Receptores Inmunológicos/metabolismo , Receptores de Prostaglandina/metabolismo , Animales , Células Cultivadas , Quimiocina CCL5/antagonistas & inhibidores , Quimiocina CCL5/metabolismo , Eosinófilos/citología , Eosinófilos/efectos de los fármacos , Eosinófilos/metabolismo , Femenino , Humanos , Hidantoínas/farmacología , Oxidorreductasas Intramoleculares/antagonistas & inhibidores , Oxidorreductasas Intramoleculares/metabolismo , Leptina/inmunología , Leucotrieno C4/inmunología , Gotas Lipídicas/inmunología , Gotas Lipídicas/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Piperidinas/farmacología , Cultivo Primario de Células , Prostaglandina D2/metabolismo , Receptores CCR3/antagonistas & inhibidores , Receptores CCR3/inmunología , Receptores Inmunológicos/antagonistas & inhibidores , Receptores Inmunológicos/inmunología , Receptores de Prostaglandina/antagonistas & inhibidores , Receptores de Prostaglandina/inmunología , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/metabolismoRESUMEN
Botrytis fruit rot, caused by Botrytis cinerea, is one of the most important strawberry diseases worldwide, and fungicide applications are often used to manage the disease in commercial production. Isolates of B. cinerea were collected from conventional and organic strawberry fields in four Brazilian States from 2013 to 2015 and their sensitivity to the main single-site mode-of action fungicides used in Brazil was tested. Resistance to azoxystrobin, iprodione, pyrimethanil, and thiophanate-methyl was found and values for effective concentration that inhibited mycelial growth by 50% were higher than 71.9, 1.2, 5.0, and 688 µg/ml, respectively, regardless the production system. Resistance to these fungicides was observed in 87.5, 76.6, 23.4, and 92.2% of isolates from conventional fields and 31.4, 22.9, 14.3, and 51.4% of isolates from organic fields, respectively. Moreover, frequencies of isolates with multiple fungicide resistance to the four active ingredients were 20.6 and 2.8% whereas 6.3 and 27.8% were sensitive to the four fungicides for conventional and organic areas, respectively. Molecular analyses of the cytochrome b, ß-tubulin, and bos1 genes revealed the presence of G143A; E198A; and I365 N/S, Q369P, or N373S mutations, respectively, in resistant isolates of B. cinerea. Field rates of fungicides sprayed preventively to inoculated strawberry fruit failed to control disease caused by the respective resistant isolates.
Asunto(s)
Botrytis/efectos de los fármacos , Farmacorresistencia Fúngica , Fragaria/microbiología , Fungicidas Industriales/farmacología , Enfermedades de las Plantas/microbiología , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/farmacología , Brasil , Frutas/microbiología , Hidantoínas/farmacología , Pirimidinas/farmacología , Estrobilurinas/farmacología , Tiofanato/farmacologíaRESUMEN
Imidazolidine derivatives, or hydantoins, are synthetic compounds with different therapeutic applications. Many imidazolidine derivatives have psychopharmacological properties, such as phenytoin, famous for its anticonvulsant efficacy, but also effective in the treatment of neuropathic pain. The hydantoin, 3-phenyl-5-(4-ethylphenyl)-imidazolidine-2,4-dione (IM-3), synthesized from the amino acid, glycine, was selected for psychopharmacological studies in mice on the basis of its chemical and structural similarity with phenytoin. The first step of this study was to define the LD50, which determined the doses of 50, 100 and 200 mg/kg for subsequent tests. The results obtained from the behavioral screening indicated that IM-3 produces decreased ambulation and analgesia in mice. Motor coordination and anxiety behavior were not affected by treatment with IM-3, as observed in the rotarod and elevated plus-maze tests, respectively. Regarding its antinociceptive properties, IM-3 showed efficacy in the acetic acid-induced writhing test by increasing the latency of the first writhe and reducing the number of writhes, as well as reducing the paw licking time in the second phase of the formalin test. The behavior of treated animals exposed to the hot plate test, however, did not differ from that of the control group. These data suggest that IM-3 has antinociceptive effects in mice, which is probably mediated by anti-inflammatory mechanisms.
Asunto(s)
Analgésicos/farmacología , Hidantoínas/farmacología , Ácido Acético , Animales , Conducta Animal , Formaldehído , Hidantoínas/química , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Ratones , Prueba de Desempeño de Rotación con Aceleración Constante , Pruebas de Toxicidad AgudaRESUMEN
Solid dispersions have been used as a strategy to improve the solubility, dissolution rate, and bioavailability of poor water-soluble drugs. The increase of the dissolution rate presented by (5Z)-3-(4-chloro-benzyl)-5-(4-nitro-benzylidene)-imidazolidine-2,4-dione (LPSF/FZ4) from the solid dispersions is related to the existence of intermolecular interactions of hydrogen bond type (>N-H···O<) between the amide group (>N-H) of the LPSF/FZ4 and the ether group (-O-) of the polyethyleneglycol polymer, or the carbonyl (C=O) of the polyvinylpyrrolidone polymer (PVP). The intensity of these interactions is directly reflected in the morphology acquired by LPSF/FZ4 in these systems, where a new solid phase, in the form of amorphous aggregates of irregular size, was identified through scanning electron microscopy and confirmed in the characterizations achieved using X-ray diffraction and thermal analysis of DSC. The solid dispersions with the polymer PVP, in higher concentrations, were revealed to be the best option to be used in the formulations of LPSF/FZ4 in both theoretical and experimental studies.
Asunto(s)
Sistemas de Liberación de Medicamentos , Hidantoínas/química , Esquistosomicidas/química , Formas de Dosificación , Portadores de Fármacos , Composición de Medicamentos , Hidantoínas/farmacología , Modelos Moleculares , Polietilenglicoles/química , Polímeros/química , Povidona/química , Esquistosomicidas/farmacología , SolubilidadRESUMEN
Thyroid hormone affects in a myriad of biological processes such as development, growth, and metabolic control. Triiodothyronine (T3) is the biologically active form of thyroid hormone that acts through nuclear receptors, TRalpha and TRbeta, regulating gene expression. Given that the distribution of these receptors is heterogeneous amongst the different tissues, it is not surprising that some physiological effects of T3 are isoform specific. For example, while TRalpha is the dominant receptor in the brain and skeletal system and mediates most of the synergism between T3 and the sympathetic signaling pathway in the heart, TRbeta is abundant in liver and is probably the isoform that mediates most of the T3 effects on lipid metabolism. Thus, it makes sense to develop compounds that selectively act on either one of the TRs, allowing for the activation of specific T3-dependent pathways. This article reviews the recent progress made in this area, focusing on the physiological effects of compounds that lower serum cholesterol and decrease fat mass, as they spare skeletal muscle and bone masses, as well as the heart. The available studies indicate that achieving selective activation of different TR-mediated pathways is a promising strategy for treating lipid disorders and obesity.
Asunto(s)
Antimetabolitos/farmacología , Metabolismo de los Lípidos/efectos de los fármacos , Termogénesis/efectos de los fármacos , Receptores alfa de Hormona Tiroidea/agonistas , Receptores beta de Hormona Tiroidea/agonistas , Triyodotironina/farmacología , Animales , Antimetabolitos/uso terapéutico , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Metabolismo Energético/efectos de los fármacos , Humanos , Hidantoínas/farmacología , Trastornos del Metabolismo de los Lípidos/tratamiento farmacológico , Trastornos del Metabolismo de los Lípidos/metabolismo , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Transducción de Señal/efectos de los fármacos , Receptores alfa de Hormona Tiroidea/metabolismo , Receptores beta de Hormona Tiroidea/metabolismo , Triyodotironina/análogos & derivados , Triyodotironina/metabolismo , Triyodotironina/uso terapéuticoRESUMEN
The objective of this work was to test and compare different techniques used in tests for compatibility between the entomopathogenic fungus Beauveria bassiana (Balsamo) Vuill and phytosanitary products, in order to develop a protocol for in vitro tests. Four modes of contact were studied between B bassiana (CG432) and the fungicides iprodione (Rovral) 500 g litre(-1) SC) and azoxystrobin (Amistar) 500 g kg(-1) WG), and the insecticide endosulfan (Thiodan) 350 g litre(-1) EC), at three rates. The techniques consisted in incorporating the products into the culture medium (IM), combining the conidia into the products mix (MP) and spraying the products before (SB) and after (SA) inoculation of the fungus on Petri dishes. The fungitoxic effect of the products was studied on the basis of parameters such as germination, colony-forming units (CFUs), vegetative growth and sporulation. The effect of azoxystrobin on conidial germination was significantly higher in the IM technique than in the other techniques. With regard to CFUs, the IM and SB techniques showed the greatest differences relative to the control. Vegetative growth and sporulation were more affected when azoxystrobin was sprayed before the fungus was applied. At the commercial rate, iprodione had a greater effect on the CFU parameter in the IM and MP techniques, and on vegetative growth in the IM technique, than the other techniques used; however, there was no significant difference occurred between the techniques at the commercial rate with respect to germination and sporulation. Endosulfan was more toxic to germination in techniques SB and SA, and to the CFUs parameter in techniques IM and MP. As to vegetative growth and sporulation, regardless of rate, a more pronounced effect was observed in IM than in the other techniques. It can be inferred that there are differences between techniques and that a standardization of the compatibility tests is necessary. Another inference is that these techniques should reflect realistic exposure of the fungus to chemical formulations under field conditions.
Asunto(s)
Ascomicetos/efectos de los fármacos , Fungicidas Industriales/farmacología , Insecticidas/farmacología , Control Biológico de Vectores/métodos , Acrilatos/farmacología , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/farmacología , Animales , Endosulfano/farmacología , Hidantoínas/farmacología , Metacrilatos , Pirimidinas/farmacología , Células Madre/efectos de los fármacos , EstrobilurinasRESUMEN
The synthesis of six benzylidene thiazolidine-diones and three benzylidene imidazolidine-diones is described. In order to investigate their antimicrobial activity, they are evaluated against micro-organism such as Staphylococcus aureus, Streptococcus feacalis, Mycobacterium smegmatis and Neurospora crassa.