RESUMEN
BACKGROUND: Insecticide resistance is a serious problem for vector control programmes worldwide. Resistance is commonly attributed to mutations at the insecticide's target site or increased activity of detoxification enzymes. METHODS: We determined the knockdown concentration (KC50) and lethal concentration (LC50) of deltamethrin in six natural populations of adult Aedes aegypti from southeastern Mexico. These populations were then selected over five generations using the LC50 from the preceding generation that underwent selection, and the heritability of deltamethrin resistance was quantified. For each generation, we also determined the frequency of the kdr alleles L410, I1016 and C1534, and the levels of activity of three enzyme families (α- and ß-esterases, mixed-function oxidases and glutathione S-transferases (GST)) associated with insecticide detoxification. RESULTS: There was an increase in KC50 and LC50 values in the subsequent generations of selection with deltamethrin (FS5vs FS0). According to the resistance ratios (RRs), we detected increases in LC50 ranging from 1.5 to 5.6 times the values of the parental generation and in KC50 ranging from 1.3-3.8 times the values of the parental generation. Triple homozygous mutant individuals (tri-locus, LL/II/CC) were present in the parental generations and increased in frequency after selection. The frequency of L410 increased from 1.18-fold to 2.63-fold after selection with deltamethrin (FS5vs FS0) in the populations analyzed; for I1016 an increase between 1.19-fold to 2.79-fold was observed, and C1534 was fixed in all populations after deltamethrin selection. Enzymatic activity varied significantly over the generations of selection. However, only α- esterase activity remained elevated in multiple populations after five generations of deltamethrin selection. We observed an increase in the mean activity levels of GSTs in two of the six populations analyzed. CONCLUSIONS: The high levels of resistance and their association with high frequencies of kdr mutations (V410L, V1016I and F1534C) obtained through artificial selection, suggest an important role of these mutations in conferring resistance to deltamethrin. We highlight the need to implement strategies that involve the monitoring of kdr frequencies in insecticide resistance monitoring and management programmes.
Asunto(s)
Resistencia a los Insecticidas/genética , Nitrilos/farmacología , Piretrinas/farmacología , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Aedes/efectos de los fármacos , Aedes/genética , Aedes/metabolismo , Animales , Esterasas/efectos de los fármacos , Esterasas/metabolismo , Genes de Insecto , Glutatión Transferasa/efectos de los fármacos , Glutatión Transferasa/metabolismo , Control de Insectos , Insecticidas/farmacología , Mosquitos Vectores/efectos de los fármacos , Mosquitos Vectores/genética , Mosquitos Vectores/metabolismo , Mutación , Oxidorreductasas/efectos de los fármacos , Oxidorreductasas/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/efectos de los fármacosRESUMEN
Chagas disease is caused by the trypanosomatid parasite Trypanosoma cruzi and threatens millions of lives in South America. As other neglected diseases there is almost no research and development effort by the pharmaceutical industry and the treatment relies on two drugs, Nifurtimox and Benznidazole, discovered empirically more than three decades ago. Nifurtimox, a nitrofurane derivative, is believed to exert its biological activity through the bioreduction of the nitro-group to a nitro-anion radical which undergoes redox-cycling with molecular oxygen. This hypothesis is generally accepted, although arguments against it have been presented. In the present work we studied the ability of Nifurtimox and five N-oxide-containing heterocycles to induce oxidative stress in T. cruzi. N-Oxide-containing heterocycles represent a promising group of new trypanosomicidal agents and their mode of action is not completely elucidated. The results here obtained argue against the oxidative stress hypothesis almost for all the studied compounds, including Nifurtimox. A significant reduction in the level of parasitic low-molecular-weight thiols was observed after Nifurtimox treatment; however, it was not linked to the production of reactive oxidant species. Besides, redox-cycling is only observed at high Nifurtimox concentrations (>400microM), two orders of magnitude higher than the concentration required for anti-proliferative activity (5microM). Our results indicate that an increase in oxidative stress is not the main mechanism of action of Nifurtimox. Among the studied N-oxide-containing heterocycles, benzofuroxan derivatives strongly inhibited parasite dehydrogenase activity and affected mitochondrial membrane potential. The indazole derivative raised intracellular oxidants production, but it was the least effective as anti-T. cruzi.
Asunto(s)
Óxidos N-Cíclicos/farmacología , Nifurtimox/farmacología , Estrés Oxidativo/efectos de los fármacos , Tripanocidas/farmacología , Trypanosoma cruzi/efectos de los fármacos , Benzoxazoles/farmacología , Células Cultivadas , Óxidos N-Cíclicos/química , Potenciales de la Membrana/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Estructura Molecular , Nifurtimox/química , Oxidación-Reducción/efectos de los fármacos , Oxidorreductasas/efectos de los fármacos , Oxidorreductasas/metabolismo , Oxígeno/metabolismo , Tripanocidas/química , Trypanosoma cruzi/crecimiento & desarrollo , Trypanosoma cruzi/metabolismoRESUMEN
Whole plants of Eichhornia crassipes and Pistia stratiotes were exposed to various concentrations (0, 0.1, 0.3, 0.5, 1.0, 3.0 and 5.0 mM) of 8 heavy metals (Ag, Cd, Cr, Cu, Hg, Ni, Pb and Zn) hydroponically for 21 days. Spectrometric assays for the total activity of catalase, peroxidase, and superoxide dismutase in the leaves were studied. At the end of the experimental period, data referred to metal treated plants were compared to data of untreated ones (control). Heavy metals increased the activity of catalase, peroxidase and superoxide dismutase in both species and there was differential inducement among metals. Overall, Zn had the least inducement of antioxidant enzymes in both species while Hg had the highest inducement. The increase in antioxidant enzymes in relation to the control plants was more in E. crassipes than P. stratiotes. The results showed that E. crassipes tolerated higher metal concentrations in a greater number of metals than P. stratiotes. Rev. Biol. Trop. 55 (3-4): 815-823. Epub 2007 December, 28.
Plantas completas de Eichhornia crassipes y Pistia stratiotes fueron expuestas a varias concentraciones (0, 0.1, 0.3, 0.5, 1.0, 3.0 and 5.0 mM) de metales pesados (Ag, Cd, Cr, Cu, Hg, Ni, Pb and Zn) utilizando hidroponía, por 21 días. Se realizaron análisis espectrométricos en las hojas para determinar la actividad total de la catalasa, peroxidasa y dismutasa superóxida. Al final del periodo experimental, se comparó con plantas no tratadas (control). Los metales pesados incrementan la actividad de la catalasa, peroxidasa y la dismutasa superóxida para ambas especies y hay diferencias entre los metales. El Zn produce el menor estímulo para enzimas antioxidantes en ambas especies; Hg produce el mayor estímulo. El incremento de las enzimas antioxidantes en relación con las plantas control fue mayor en E. crassipes que P. stratiotes. E. crassipes tolera altas concentraciones de metal en un gran número de ellos, mientras que la tolerancia en P. stratiotes es menor.
Asunto(s)
Araceae/efectos de los fármacos , Eichhornia/efectos de los fármacos , Metales Pesados/farmacología , Oxidorreductasas/efectos de los fármacos , Araceae/enzimología , Catalasa/efectos de los fármacos , Eichhornia/enzimología , Peroxidasa/efectos de los fármacos , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/enzimología , Superóxido Dismutasa/efectos de los fármacosRESUMEN
En el presente trabajo se estudió el efecto de la administración intramuscular de 30.000, 50.000 y 100.000 UI de palmitato de vitamina A/día, durante 7 días, respectivamente, sobre la actividad enzimática hepática en 45 ratas Wistar machos, de 12 semanas de edad, con pesos entre 180 y 200 gramos. El grupo control estuvo integrado por 15 ratas Wistar sanas, con género, edad y peso similares a los animales tratados. El consumo de alimentos y de agua, y el peso de las ratas se determinó al finalizar el período experimental. Las ratas se examinaron en busca de manifestaciones clínicas de toxicidad. Al final el estudio, las ratas se sacrificaron bajo anestesia con éter y se tomaron muestras de tejido hepático para la determinación de la actividad enzimática. La administración de vitamina A en exceso incrementó de manera significativa (p menor que 0,05) el contenido hepático del retinol, determinó diversos y variados signos clínicos (tales como: anorexia, pérdida de peso, alopecia, conjuntivitis, hemorragias internas y externas, alteraciones cutáneas y muerte de los animales) e incrementó (p menor que 0,05) la actividad de las siguientes enzimas: alanina aminotransferasa, aspartato aminotransferasa, maltasa ácida (alfa-1,4-glucosidasa ácida), proteasas ácidas, lactato dehidrogenasa y fosfatasa alcalina mientras que las actividades de la glucosa-6-fosfatasa, glucógeno fosforilasa, alfa-amilasa, colinesterasa y arginasa disminuyeron (p menor que 0,05) al comparar con los controles no tratados. Estos cambios son proporcionales a las dosis inyectadas de vitamina A. En conclusión, nuestros resultados proporcionan evidencias que la administración de dosis altas de vitamina A a corto plazo determina diversos y variados signos clínicos y produce una marcada alteración de la actividad enzimática hepática.
In the present work the effect of intramuscular administration of 30.000, 50.000 and 100.000 IU of vitamin A palmitate daily for seven days, respectively, on the liver enzyme activity in 45 white male Wistar rats, aged 12 weeks and weighing 180-200 g, have been studied. The group control was integrated by 15 healthy rats with similar characteristics (strain, gender, age and weight) to treated animals. Food and water consumption and body weights were recorded at the end of the experimental period. Rats were observed for clinical signs of toxicity. At the end of the study, rats were sacrificed under ether anesthesia. Liver samples were taken for the determination of enzyme activity. Administration of excess of vitamin A produced a significant (p menor 0.05) increase in the content of liver vitamin A, determined diverse and variable clinical signs (such as, anorexia, loss of body weight, alopecia, conjunctivitis, external and internal hemorrhages, skin abnormalities and death) and increased (p menor que 0.05) the activity of the following enzymes: alanine aminotransferase, aspartate aminotransferase, acid maltase (acid alfa-1,4-glucosidase), acid proteases, lactate dehydrogenase and alkaline phosphatase while glucose-6-phosphatase, glycogen phosphorylase, alfa-amylase, cholinesterase and arginase decreased (p menor que 0.05) as compared with untreated controls. These changes depend on the doses given of vitamin A. In conclusion, our results provide evidence that short-term administration of high doses of vitamin A determined diverse and variable clinical signs and produces a marked alteration of activity of liver enzymes.
Asunto(s)
Animales , Masculino , Ratas , Antioxidantes/administración & dosificación , Hidrolasas/efectos de los fármacos , Hipervitaminosis A/enzimología , Hígado/enzimología , Oxidorreductasas/efectos de los fármacos , Transferasas/efectos de los fármacos , Vitamina A/administración & dosificación , Vitamina A/análogos & derivados , Enfermedad Aguda , Antioxidantes/farmacología , Hidrolasas/análisis , Inyecciones Intramusculares , Hígado/efectos de los fármacos , Oxidorreductasas/análisis , Ratas Wistar , Transferasas/análisis , Vitamina A/farmacologíaRESUMEN
Whole plants of Eichhornia crassipes and Pistia stratiotes were exposed to various concentrations (0, 0.1, 0.3, 0.5, 1.0, 3.0 and 5.0 mM) of 8 heavy metals (Ag, Cd, Cr, Cu, Hg, Ni, Pb and Zn) hydroponically for 21 days. Spectrometric assays for the total activity of catalase, peroxidase, and superoxide dismutase in the leaves were studied. At the end of the experimental period, data referred to metal treated plants were compared to data of untreated ones (control). Heavy metals increased the activity of catalase, peroxidase and superoxide dismutase in both species and there was differential inducement among metals. Overall, Zn had the least inducement of antioxidant enzymes in both species while Hg had the highest inducement. The increase in antioxidant enzymes in relation to the control plants was more in E. crassipes than P. stratiotes. The results showed that E. crassipes tolerated higher metal concentrations in a greater number of metals than P. stratiotes.
Asunto(s)
Araceae/efectos de los fármacos , Eichhornia/efectos de los fármacos , Metales Pesados/farmacología , Oxidorreductasas/efectos de los fármacos , Araceae/enzimología , Catalasa/efectos de los fármacos , Eichhornia/enzimología , Peroxidasa/efectos de los fármacos , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/enzimología , Superóxido Dismutasa/efectos de los fármacosRESUMEN
The schistosomicidal properties of Nigella sativa seeds were tested in vitro against Schistosoma mansoni miracidia, cercariae, and adult worms. Results indicate its strong biocidal effects against all stages of the parasite and also showed an inhibitory effect on egg-laying of adult female worms. In the present work we also studied the effects of crushed seeds on some antioxidant enzymes; which have a role in protection of adult worms against host oxidant killing; as well as some enzymes of glucose metabolism; which have a crucial role in the survival of adult worms inside their hosts. The data revealed that the used drug induce an oxidative stress against adult worms which indicated by a decrease in the activities of both antioxidant enzymes, superoxide dismutase, glutathione peroxidase, and glutathione reductase and enzymes of glucose metabolism, hexokinase and glucose-6-phosphate dehydrogenase. Disturbing of such enzymes of adult worms using N. sativa seeds could in turn render the parasite vulnerable to damage by the host and may play a role in the antischistosomal potency of the used drug.
Asunto(s)
Nigella , Oxidorreductasas/efectos de los fármacos , Schistosoma mansoni/efectos de los fármacos , Esquistosomicidas/farmacología , Semillas , Animales , Femenino , Dosificación Letal Mediana , Schistosoma mansoni/enzimología , Schistosoma mansoni/crecimiento & desarrolloRESUMEN
The schistosomicidal properties of Nigella sativaseeds were tested in vitro against Schistosoma mansoni miracidia, cercariae, and adult worms. Results indicate its strong biocidal effects against all stages of the parasite and also showed an inhibitory effect on egg-laying of adult female worms. In the present work we also studied the effects of crushed seeds on some antioxidant enzymes; which have a role in protection of adult worms against host oxidant killing; as well as some enzymes of glucose metabolism; which have a crucial role in the survival of adult worms inside their hosts. The data revealed that the used drug induce an oxidative stress against adult worms which indicated by a decrease in the activities of both antioxidant enzymes, superoxide dismutase, glutathione peroxidase, and glutathione reductase and enzymes of glucose metabolism, hexokinase and glucose-6-phosphate dehydrogenase. Disturbing of such enzymes of adult worms using N. sativa seeds could in turn render the parasite vulnerable to damage by the host and may play a role in the antischistosomal potency of the used drug.
Asunto(s)
Animales , Femenino , Nigella , Oxidorreductasas/efectos de los fármacos , Semillas , Schistosoma mansoni/efectos de los fármacos , Esquistosomicidas/farmacología , Schistosoma mansoni/enzimología , Schistosoma mansoni/crecimiento & desarrolloRESUMEN
The fomesafen and 2,4-D amine herbicide induce cytotoxic effects at hepatic level in rats, such as: hepatomegaly, hyperplasia and increase in the enzymes activity which participate in the processes of peroxisomal beta-oxidation of fatty acids. In this work, the effect of vitamin E and C was evaluated, as well as, the dexamethasone in the modulation of these hepatotoxic effects. Sprague-Dawley rats were treated with the herbicides and with the agents to be evaluated. The different treatments were given during 15 days orally route. The herbicides combined with the dexamethasone and antioxidant agents were administrated only and simultaneously with the herbicides. Once concluded the different treatment, the rats were weighed and sacrificed. It was evaluated the liver size and liver fragments were obtained to determine the enzymatic activity of Fatty Acyl CoA-oxidase (FACO) and cellular number. The results showed that the hepatomegaly induced by fomesafen was inhibited by the vitamins and by the dexamethasone, while any effect was not observed in the group of rats treated with 2,4-D amine. None of the agents modulated the FACO activity induced by herbicides in treated rats. However, the dexamethasone showed a protective effect in the hyperplasia induced by two herbicides. The hepatotoxic effects induced by the herbicides responded to a different mechanism due to the differences of the effects observed at the antioxidant agents. On the other hand, the inhibition of the cellular proliferation by the dexamethasone does not keep relation with the responsible mechanisms of inducing the oxidant stress into FACO activity. Under experimental conditions of this study, the use of these agents does not guarantee protection against the hepatotoxic effects induced by the herbicides.
Asunto(s)
Ácido 2,4-Diclorofenoxiacético/antagonistas & inhibidores , Antioxidantes/farmacología , Benzamidas/antagonistas & inhibidores , Enfermedad Hepática Inducida por Sustancias y Drogas , Dexametasona/farmacología , Dimetilaminas/antagonistas & inhibidores , Herbicidas/antagonistas & inhibidores , Vitaminas/farmacología , Ácido 2,4-Diclorofenoxiacético/toxicidad , Acil-CoA Oxidasa , Animales , Ácido Ascórbico/farmacología , Benzamidas/toxicidad , Dimetilaminas/toxicidad , Hepatomegalia/inducido químicamente , Herbicidas/toxicidad , Hiperplasia/inducido químicamente , Hígado/efectos de los fármacos , Hígado/enzimología , Masculino , Oxidorreductasas/efectos de los fármacos , Oxidorreductasas/metabolismo , Ratas , Ratas Sprague-Dawley , Vitamina E/farmacologíaRESUMEN
Microcin J25 (MccJ25) is a cyclic peptide of 21 unmodified amino acid residues produced by a fecal strain of Escherichia coli. It has previously been shown that the antibiotic activity of this peptide is mainly directed to Enterobacteriaceae, including several pathogenic E. coli, Salmonella and Shigella strains. In this paper we show that MccJ25 acts on the cytoplasmic membrane of Salmonella newport cells producing alteration of membrane permeability, and the subsequent gradient dissipation, that initiate the inhibition of process, such as oxygen consumption. These results, taken together with our in vitro observations [Rintoul et al. (2000) Biochim. Biophys. Acta 1509, 65-72], strongly suggest that the disruption of the cytoplasmic membrane gradient is closely related to the bactericidal activity of MccJ25 in S. newport.
Asunto(s)
Antibacterianos/farmacología , Bacteriocinas/farmacología , Membrana Celular/efectos de los fármacos , Escherichia coli/metabolismo , Péptidos , Salmonella/efectos de los fármacos , Permeabilidad de la Membrana Celular/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Humanos , Potenciales de la Membrana/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Oxidorreductasas/efectos de los fármacos , Consumo de Oxígeno/efectos de los fármacos , Salmonella/crecimiento & desarrollo , Salmonella/patogenicidadRESUMEN
Both P450 aromatase (P450arom) and 17beta-hydroxysteroid dehydrogenase (17HSD) type 1 are key enzymes in the ovarian E(2) biosynthesis. Cytokines have been suggested to be mediators between the immune and the reproductive systems, and they may play a role as paracrine or autocrine ovarian regulatory factors. Interleukin-1 (IL-1) and tumor necrosis factor alpha (TNFalpha) have been shown to modulate the FSH-induced E(2) production in immature rat granulosa cells. The aim of the present study was to investigate the effects of these cytokines on the activity and expression of the 17HSD type 1 enzyme in cultured undifferentiated granulosa cells. Furthermore, the expression of P450arom was also analyzed. The granulosa cells obtained from the ovaries of immature DES-treated rats were initially cultured for 48 h with no other treatment and then incubated with or without the test reagents for an additional 48 h. The treatment of the granulosa cells with cytokines alone did not affect the activity of 17HSD type 1 as assessed by the conversion of tritiated substrate. However, both TNFalpha and IL-1beta caused a dose-dependent inhibition of the recombinant FSH-induced enzyme activity and the Forskoline-induced expression of 17HSD type 1 and P450arom mRNAs. The cytokines only slightly inhibited the 8-Br-cAMP-induced P450arom expression. In contrast, the inhibitory cytokine effects on 17HSD type 1 expression and activity were not abolished by the presence of 8-Br-cAMP. Despite the presence of inhibitors of protein kinase C (staurosporine) or tyrosine kinases (genistein), the inhibitory effects of TNFalpha and IL-1beta on the Forskoline-induced expression of 17HSD type 1 and P450arom and the Forskoline-induced 17HSD activity were not blocked. The data show a dose dependent inhibitory effect of TNFalpha and IL-1beta on gonadotropin action, opposite to the follicular development by down-regulating the expressions of estrogen biosynthetic enzymes. The cytokine effects on P450arom expression are mainly derived from a decrease in gonadotropin-induced cAMP production, while the inhibitory mechanisms on 17HSD type 1 expression involve distal sites from cAMP generation. The protein kinase C and tyrosine kinase pathways are likely not to be involved in the latter mechanisms.
Asunto(s)
Citocinas/farmacología , Estradiol/biosíntesis , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Oxidorreductasas/efectos de los fármacos , 17-Hidroxiesteroide Deshidrogenasas/efectos de los fármacos , Animales , Aromatasa/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Femenino , Hormona Folículo Estimulante/farmacología , Células de la Granulosa/citología , Células de la Granulosa/metabolismo , Interleucina-1/farmacología , Oxidorreductasas/genética , Oxidorreductasas/metabolismo , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
El surgimiento de resistencia en poblaciones de insectos es uno de los efectos indeseables asociados al uso de insecticidas, y es un buen ejemplo del modo en que ocurren los procesos microevolutivos. En 1908 se documentó por primera vez la existencia de insectos resistentes a insecticidas. Ahora se conocen casos de resistencia en más de 500 especies de artrópodos. Los principales mecanismos que confieren resistencia a insecticidas son penetración cuticular reducida, metabolismo degradativo aumentado y reducción en la susceptibilidad de los sitios de acción. Los métodos de la biología molecular permiten identificar las bases moleculares de esos mecanismos. El propósito de este artículo es reseñar el conocimiento disponible acerca de la biología molecular de la resistencia a insecticidas: mutaciones puntuales en genes de acetilcolinesterasa (Drosophila melanogaster) y del receptor de GABA (varias especies), inserciones en genes de transferasas (D. melanogaster) y del citocromo P450 (D. melanogaster), amplificación de genes de esterasas (Myzus persicae y Culex pipiens / quinquefasciatus complex), cambios que afectan la expresión del gen del citocromo P450 (Musca domestica), y una mutación ligada al gen del canal de sodio dependiente de voltaje (M. domestica)
Asunto(s)
Resistencia a los Insecticidas/genética , Insecticidas/efectos adversos , Insectos/efectos de los fármacos , Control de Plagas/normas , Acetilcolinesterasa/efectos de los fármacos , Acetilcolinesterasa/genética , Aedes/efectos de los fármacos , Culicidae/efectos de los fármacos , Sistema Enzimático del Citocromo P-450/efectos de los fármacos , Sistema Enzimático del Citocromo P-450/genética , Drosophila melanogaster/efectos de los fármacos , Esterasas/efectos de los fármacos , Esterasas/genética , Control de Insectos/normas , Control de Insectos/tendencias , Insecticidas/clasificación , Moscas Domésticas , Oxidorreductasas/efectos de los fármacos , Oxidorreductasas/genética , Receptores de GABA/efectos de los fármacos , Receptores de GABA/genética , Transferasas/efectos de los fármacos , Transferasas/genéticaRESUMEN
El surgimiento de resistencia en poblaciones de insectos es uno de los efectos indeseables asociados al uso de insecticidas, y es un buen ejemplo del modo en que ocurren los procesos microevolutivos. En 1908 se documentó por primera vez la existencia de insectos resistentes a insecticidas. Ahora se conocen casos de resistencia en más de 500 especies de artrópodos. Los principales mecanismos que confieren resistencia a insecticidas son penetración cuticular reducida, metabolismo degradativo aumentado y reducción en la susceptibilidad de los sitios de acción. Los métodos de la biología molecular permiten identificar las bases moleculares de esos mecanismos. El propósito de este artículo es reseñar el conocimiento disponible acerca de la biología molecular de la resistencia a insecticidas: mutaciones puntuales en genes de acetilcolinesterasa (Drosophila melanogaster) y del receptor de GABA (varias especies), inserciones en genes de transferasas (D. melanogaster) y del citocromo P450 (D. melanogaster), amplificación de genes de esterasas (Myzus persicae y Culex pipiens / quinquefasciatus complex), cambios que afectan la expresión del gen del citocromo P450 (Musca domestica), y una mutación ligada al gen del canal de sodio dependiente de voltaje (M. domestica) (AU)
Asunto(s)
Resistencia a los Insecticidas/genética , Insecticidas/efectos adversos , Control de Plagas/normas , Insectos/efectos de los fármacos , Sistema Enzimático del Citocromo P-450/efectos de los fármacos , Sistema Enzimático del Citocromo P-450/genética , Acetilcolinesterasa/efectos de los fármacos , Acetilcolinesterasa/genética , Receptores de GABA/efectos de los fármacos , Receptores de GABA/genética , Transferasas/efectos de los fármacos , Transferasas/genética , Esterasas/efectos de los fármacos , Esterasas/genética , Insecticidas/clasificación , Moscas Domésticas/efectos de los fármacos , Drosophila melanogaster/efectos de los fármacos , Culicidae/efectos de los fármacos , Aedes/efectos de los fármacos , Oxidorreductasas/efectos de los fármacos , Oxidorreductasas/genética , Control de Insectos/normas , Control de Insectos/tendenciasRESUMEN
The use of antineoplastics is common in cancer therapy, and some of them have been associated with the development of porphyria in patients with cancer. However, knowledge of their effects on the haeme metabolic pathway is at present scarce and unclear. So, the present study evaluates the porphyrinogenic ability of nine antineoplastics (both alkylating and non-alkylating). These were tested either alone or in conjunction with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (latent porphyria model) in chick embryos and in mice. The results obtained suggest that the use of cyclophosphamide, azathioprine, 5-fluorouracil, busulphan, procarbazine and hexamethylmelamine be avoided in the treatment of porphyric patients. On the other hand, dacarbazine, chlorambucil and melphalan are non-porphyrinogenic. We also provide evidence showing that neither the presence of the mustard group in the structure of the antineoplastic nor alterations in ferrochelatase or protoporphyrinogen oxidase activities are responsible for the porphyrinogenic ability of cyclophosphamide.