RESUMO
DDT, a persistent organic pollutant, remains affecting human health worldwide. DDT and its most persistent metabolite (p,p'-DDE) negatively affect the immune response regulation and mechanisms involved in protecting against pathogens Such metabolite decreases the capability to limit intracellular growth of Mycobacterium microti and yeast. However, the effect on unstimulated (M0) and anti-inflammatory macrophages (M2) has been evaluated scanty. Herein, we evaluated the impact of p,p'-DDE at environmentally relevant concentrations (0.125, 1.25, 2.5, and 5 µg/mL) on bone marrow-derived macrophages stimulated with IFNγ+LPS to M1 or with IL-4 +IL-13 to M2. Thus we study whether the p,p'-DDE induces M0 to a specific phenotype or modulates activation of the macrophage phenotypes and explains, at least partly, the reported effects of p,p'-DDE on the M1 function. The p,p'-DDE did not affect the cell viability of M0 or the macrophage phenotypes. In M1, the p,p'-DDE decreased NOâ¢- production and IL-1ß secretion, but increasing cellular ROS and mitochondrial O2â¢-, but did not alter iNOS, TNF-α, MHCII, and CD86 protein expression nor affect M2 markers arginase activity, TGF-ß1, and CD206; p,p'-DDE, did not affect marker expression in M0 or M2, supporting that its effects on M1 parameters are not dependent on M0 nor M2 modulation. The decreasing of NOâ¢- production by the p,p'-DDE without altering iNOS levels, Arginase activity, or TNF-α, but increasing cellular ROS and mitochondrial O2 suggests that p,p'-DDE interferes with the iNOS function but not with its transcription. The p,p'-DDE decreasing of IL-1ß secretion, without any effect on TNF-α, suggest that an alteration of specific targets involved in IL-1ß secretion may be affected and related to ROS induction. The p,p'-DDE effect on iNOS function and the IL-1ß secretion process, as the NLRP3 activation, deserves further study.
Assuntos
Diclorodifenil Dicloroetileno , Macrófagos , Animais , Humanos , Camundongos , Arginase/genética , Arginase/metabolismo , Arginase/farmacologia , DDT/metabolismo , DDT/farmacologia , Diclorodifenil Dicloroetileno/toxicidade , Diclorodifenil Dicloroetileno/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos Endogâmicos BALB C , Fenótipo , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/genéticaRESUMO
Environmental endocrine disruptor chemicals are substances that can alter the homeostasis of the endocrine system in living organisms. They can be released from several products used in daily activities. Once in the organism, they can disrupt the endocrine function by mimicking or blocking naturally occurring hormones due to their similar chemical structure. This endocrine disruption is the most important cause of the wellknown hormoneassociate types of cancer. Additionally, it is decisive to determine the susceptibility of each organ to these compounds. Therefore, the present review aimed to summarize the effect of different environmental substances such as bisphenol A, dichlorodiphenyltrichloroethane and polychlorinated biphenyls in both the mammary and the prostate tissues. These organs were chosen due to their association with the hormonal system and their common features in carcinogenic mechanisms. Outcomes derived from the present review may provide evidence that should be considered in future debates regarding the effects of endocrine disruptors on carcinogenesis.
Assuntos
Disruptores Endócrinos/farmacologia , Poluentes Ambientais/farmacologia , Glândulas Mamárias Animais/efeitos dos fármacos , Próstata/efeitos dos fármacos , Animais , Compostos Benzidrílicos/farmacologia , DDT/farmacologia , Feminino , Humanos , Masculino , Glândulas Mamárias Humanas/efeitos dos fármacos , Fenóis/farmacologia , Bifenilos Policlorados/farmacologiaRESUMO
BACKGROUND: Knockdown resistance (kdr) is a well-characterized target-site insecticide resistance mechanism that is associated with DDT and pyrethroid resistance. Even though insecticide resistance to pyrethroids and DDT have been reported in Anopheles albimanus, Anopheles benarrochi sensu lato (s.l.), Anopheles darlingi, Anopheles nuneztovari s.l., and Anopheles pseudopunctipennis s.l. malaria vectors in Latin America, there is a knowledge gap on the role that kdr resistance mechanisms play in this resistance. The aim of this study was to establish the role that kdr mechanisms play in pyrethroid and DDT resistance in the main malaria vectors in Colombia, in addition to previously reported metabolic resistance mechanisms, such as mixed function oxidases (MFO) and nonspecific esterases (NSE) enzyme families. METHODS: Surviving (n = 62) and dead (n = 67) An. nuneztovari s.l., An. darlingi and An. albimanus mosquitoes exposed to diagnostic concentrations of DDT and pyrethroid insecticides were used to amplify and sequence a ~ 225 bp fragment of the voltage-gated sodium channels (VGSC) gene. This fragment spanning codons 1010, 1013 and 1014 at the S6 segment of domain II to identify point mutations, which have been associated with insecticide resistance in different species of Anopheles malaria vectors. RESULTS: No kdr mutations were detected in the coding sequence of this fragment in 129 samples, 62 surviving mosquitoes and 67 dead mosquitoes, of An. darlingi, An. nuneztovari s.l. and An. albimanus. CONCLUSION: Mutations in the VGSC gene, most frequently reported in other species of the genus Anopheles resistant to pyrethroid and DDT, are not associated with the low-intensity resistance detected to these insecticides in some populations of the main malaria vectors in Colombia. These results suggest that metabolic resistance mechanisms previously reported in these populations might be responsible for the resistance observed.
Assuntos
Anopheles/genética , DDT/farmacologia , Resistência a Inseticidas/genética , Inseticidas/farmacologia , Mosquitos Vetores/genética , Piretrinas/farmacologia , Animais , Anopheles/efeitos dos fármacos , Colômbia , Malária , Especificidade da EspécieRESUMO
BACKGROUND: Epidemics of dengue, chikungunya and Zika are a growing threat to areas where Aedes aegypti are present. The efficacy of chemical control of Ae. aegypti is threatened by the increasing frequency of insecticide resistance. The objective of this study was to determine the susceptibility status as well as the biochemical and molecular mechanisms underlying insecticide resistance in three populations of Ae. aegypti in high risk areas of dengue, chikungunya, and Zika in Peru. METHODS: Bioassays were conducted on adult Ae. aegypti to evaluate their susceptibility to insecticides used currently or historically for mosquito control in Peru, including six pyrethroids, three organophosphates and one organochlorine, in populations of Ae. aegypti from the districts of Chosica (Department of Lima), Punchana (Department of Loreto) and Piura (Department of Piura). Resistance mechanisms were determined by biochemical assays to assess activity levels of key detoxification enzyme groups (nonspecific esterases, multi-function oxidases, glutathione S-transferases and insensitive acetylcholinesterase). Real-time PCR assays were used to detect two kdr mutations (V1016I and F1534C) on the voltage-gated sodium channel gene. RESULTS: Resistance to DDT was detected in all three populations, and resistance to pyrethroids was detected in all populations except the population from Chosica, which still exhibited susceptibility to deltamethrin. Resistance to organophosphates was also detected, with the exception of populations from Punchana and Piura, which still demonstrated susceptibility to malathion. In general, no increase or alteration of activity of any enzyme group was detected. Both 1016I and 1534C alleles were detected in Punchana and Piura, while only the 1534C allele was detected in Chosica. CONCLUSIONS: The results suggest that resistance to multiple classes of insecticides exist in areas important to Ae. aegypti-borne disease transmission in Peru. The F1534C mutation was present in all 3 populations and the V1016I mutation was present in 2 populations. To our knowledge, this is the first report of the presence of 1016I and 1534C in Ae. aegypti in Peru. The absence of highly elevated enzymatic activity suggests that target site resistance is a key mechanism underlying insecticide resistance in these populations, although further research is needed to fully understand the role of metabolic resistance mechanisms in these populations.
Assuntos
Aedes/fisiologia , Resistência a Inseticidas/fisiologia , Inseticidas/farmacologia , Mosquitos Vetores/fisiologia , Aedes/efeitos dos fármacos , Animais , Bioensaio , DDT/farmacologia , Malation/farmacologia , Mosquitos Vetores/efeitos dos fármacos , Nitrilas/farmacologia , Organofosfatos/farmacologia , Peru , Piretrinas/farmacologiaRESUMO
BACKGROUND: Aedes aegypti and Ae. albopictus are two highly invasive mosquito species, both vectors of several viruses, including dengue, chikungunya and Zika. While Ae. aegypti is the primary vector in the tropics and sub-tropics, Ae. albopictus is increasingly under the public health watch as it has been implicated in arbovirus-transmission in more temperate regions, including continental Europe. Vector control using insecticides is the pillar of most control programmes; hence development of insecticide resistance is of great concern. As part of a Brazilian-Swiss Joint Research Programme we set out to assess whether there are any signs of existing or incipient insecticide resistance primarily against the larvicide Bacillus thuringiensis svar. israelensis (Bti), but also against currently applied and potentially alternative insecticides in our areas, Recife (Brazil) and the Swiss-Italian border region. METHODS: Following World Health Organization guidelines, dose-response curves for a range of insecticides were established for both colonized and field caught Ae. aegypti and Ae. albopictus. The larvicides included Bti, two of its toxins, Cry11Aa and Cry4Ba, Lysinibacillus sphaericus, Vectomax CG®, a formulated combination of Bti and L. sphaericus, and diflubenzuron. In addition to the larvicides, the Swiss-Italian Ae. albopictus populations were also tested against five adulticides (bendiocarb, dichlorodiphenyltrichloroethane, malathion, permethrin and λ-cyhalothrin). RESULTS: Showing a similar dose-response, all mosquito populations were fully susceptible to the larvicides tested and, in particular, to Bti which is currently used both in Brazil and Switzerland. In addition, there were no signs of incipient resistance against Bti as larvae were equally susceptible to the individual toxins, Cry11Aa and Cry4Ba. The field-caught Swiss-Italian populations were susceptible to the adulticides tested but DDT mortality rates showed signs of reduced susceptibility. CONCLUSIONS: The insecticides currently used for mosquito control in Switzerland and Brazil are still effective against the target populations. The present study provides an important reference as relatively few insecticide susceptibility surveys have been carried out with Ae. albopictus.
Assuntos
Aedes/efeitos dos fármacos , Agentes de Controle Biológico/farmacologia , Inseticidas/farmacologia , Animais , Bacillus thuringiensis/fisiologia , Agentes de Controle Biológico/química , Brasil/epidemiologia , DDT/farmacologia , Dengue/epidemiologia , Dengue/transmissão , Resistência a Inseticidas , Itália/epidemiologia , Larva/efeitos dos fármacos , Controle de Mosquitos , Nitrilas/farmacologia , Permetrina/farmacologia , Piretrinas/farmacologia , Suíça/epidemiologia , Organização Mundial da Saúde , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/transmissãoRESUMO
BACKGROUND: To evaluate the insecticide susceptibility status of Aedes aegypti (L.) in Colombia, and as part of the National Network of Insecticide Resistance Surveillance, 12 mosquito populations were assessed for resistance to pyrethroids, organophosphates and DDT. Bioassays were performed using WHO and CDC methodologies. The underlying resistance mechanisms were investigated through biochemical assays and RT-PCR. RESULTS: All mosquito populations were susceptible to malathion, deltamethrin and cyfluthrin, and highly resistant to DDT and etofenprox. Resistance to lambda-cyhalothrin, permethrin and fenitrothion ranged from moderate to high in some populations from Chocó and Putumayo states. In Antioquia state, the Santa Fe population was resistant to fenitrothion. Biochemical assays showed high levels of both cytochrome P450 monooxygenases (CYP) and non-specific esterases (NSE) in some of the fenitrothion- and pyrethroid-resistant populations. All populations showed high levels of glutathione-S-transferase (GST) activity. GSTe2 gene was found overexpressed in DDT-resistant populations compared with Rockefeller susceptible strain. CONCLUSIONS: Differences in insecticide resistance status were observed between insecticides and localities. Although the biochemical assay results suggest that CYP and NSE could play an important role in the pyrethroid and fenitrothion resistance detected, other mechanisms remain to be investigated, including knockdown resistance. Resistance to DDT was high in all populations, and GST activity is probably the main enzymatic mechanism associated with this resistance. The results of this study provide baseline data on insecticide resistance in Colombian A. aegypti populations, and will allow comparison of changes in susceptibility status in this vector over time.
Assuntos
Aedes/efeitos dos fármacos , Resistência a Inseticidas , Inseticidas/farmacologia , Aedes/genética , Aedes/metabolismo , Animais , Colômbia , DDT/farmacologia , Expressão Gênica/efeitos dos fármacos , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Permetrina/farmacologia , Piretrinas/farmacologiaRESUMO
Bioassays and biochemical assays were conducted on eight Trinidadian strains of Aedes aegypti larvae to determine the involvement of biochemical mechanisms in resistance to insecticides. Larval strains were assayed to dichlorodiphenyltrichloroethane (DDT), bendiocarb, temephos and permethrin, using the Centers for Disease Control and Prevention (CDC) time-mortality bioassay method. A Resistance Threshold (RT) was calculated for each insecticide in relation to the CAREC reference susceptible Ae. aegypti strain and larval strains with <80% mortality were considered to be resistant. Biochemical assays were performed to determine the activities of nonspecific esterases (α- and ß-), PNPA-esterases, mixed function oxidases (MFO), glutathione-S-transferases (GST) and acetylcholinesterase (AChE) enzymes which are involved in insecticide resistance in mosquitoes. Enzyme profiles of each strain were compared with those of the CAREC reference susceptible strain by Kruskal-Wallis and Dunn's multiple comparison tests (p<0.05). The CAREC 99th percentile was calculated for each enzyme and the percentage of individuals with enzyme activities above that of the CAREC 99th percentile was calculated. Activities were classified as unaltered (<50%), incipiently altered (15-50%) or altered (>50%) for each strain. The established RTs for permethrin and bendiocarb were 30 and 75 min, respectively; and 120 min for DDT and temephos. All strains were resistant to DDT (1.00-40.25% mortality) and temephos (11.50-74.50% mortality) while six strains were resistant to bendiocarb (51.50-78.50% mortality) and five to permethrin (6.50-42.50% mortality). Biochemical assays revealed that the median activity levels for all enzymes varied significantly (p<0.05). The Curepe strain had incipiently altered levels of α-esterase while the other seven strains had altered activity with five of them registering 100%. The St Clair strain showed altered activity levels of ß-esterase while three strains had incipiently altered levels. The majority of strains had altered activity of MFO enzymes but only the St Clair strain showed altered activity of GST. PNPA-esterases activity was unaltered in all strains and only the Haleland Park strain showed altered remaining AChE activity in the presence of propoxur. Elevated levels of enzymes (incipiently altered or altered), except in the case of PNPA-esterases, show that biochemical resistance may play an important role in the manifestation of insecticide resistance in Trinidadian populations of Ae. aegypti. It is therefore important for insecticide resistance surveillance to be ongoing as the detection of resistance before it spreads throughout an entire population makes it possible for early intervention.
Assuntos
Aedes/efeitos dos fármacos , Resistência a Inseticidas , Inseticidas/farmacologia , Aedes/enzimologia , Animais , DDT/farmacologia , Enzimas/metabolismo , Permetrina/farmacologia , Fenilcarbamatos/farmacologia , Análise de Sobrevida , Fatores de Tempo , Trinidad e TobagoRESUMO
The inhibitory effects on esterases and phospholipase A2 (PLA2) in the freshwater rotifer Euchlanis dilatata, native to Mexico, were assessed by fluorimetry after in vivo exposure (30 min) in laboratory conditions to sublethal concentrations of metals and pesticides. EC(50) values for esterases ranged from 7.9 × 10(-7) for DDT to 61.9 µg l(-1) for methyl parathion, while corresponding values for PLA2 ranged from 0.96 × 10(-6) for mercury to 69.2 µg l(-1) for lead. These enzyme systems in E. dilatata are very sensitive to the tested agents and suggest they would be suitable biomarkers. However, sensitivity to other environmental contaminants should be investigated in laboratory conditions and field studies to assess their potential as environmental biomarkers.
Assuntos
Inibidores Enzimáticos/farmacologia , Enzimas/metabolismo , Metais Pesados/farmacologia , Praguicidas/farmacologia , Rotíferos/efeitos dos fármacos , Rotíferos/enzimologia , Poluição Química da Água/análise , Estruturas Animais/efeitos dos fármacos , Estruturas Animais/enzimologia , Animais , Animais Recém-Nascidos , Biocatálise/efeitos dos fármacos , Biomarcadores/metabolismo , Cádmio/farmacologia , Cádmio/toxicidade , DDT/farmacologia , DDT/toxicidade , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/toxicidade , Esterases/antagonistas & inibidores , Esterases/metabolismo , Corantes Fluorescentes/metabolismo , Chumbo/farmacologia , Chumbo/toxicidade , Dose Letal Mediana , Cloreto de Mercúrio/farmacologia , Cloreto de Mercúrio/toxicidade , Metais Pesados/toxicidade , Metil Paration/farmacologia , Metil Paration/toxicidade , Praguicidas/toxicidade , Inibidores de Fosfolipase A2 , Fosfolipases A2/metabolismoRESUMO
The Grand Cayman population of Aedes aegypti is highly resistant to DDT and pyrethroid insecticides. Glutathione transferase, cytochrome P450, and esterase levels were increased in the Grand Cayman population relative to a susceptible laboratory strain, but synergist studies did not implicate elevated insecticide detoxification as a major cause of resistance. The role of target site resistance was therefore investigated. Two substitutions in the voltage-gated sodium channel were identified, V1016I in domain II, segment 6 (IIS6) (allele frequency = 0.79) and F1534C in IIIS6 (allele frequency = 0.68). The role of the F1534C mutation in conferring resistance to insecticides has not been previously established and so a tetraplex polymerase chain reaction assay was designed and used to genotype mosquitoes that had been exposed to insecticides. The F1534C mutation was strongly correlated with resistance to DDT and permethrin.
Assuntos
Aedes/efeitos dos fármacos , Resistência a Inseticidas , Inseticidas/farmacologia , Piretrinas/farmacologia , Aedes/genética , Aedes/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Bioensaio , DDT/farmacologia , Feminino , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Insetos Vetores/efeitos dos fármacos , Insetos Vetores/genética , Insetos Vetores/metabolismo , Canais de Sódio/genética , Índias OcidentaisRESUMO
Enhanced metabolism by oxidative enzymes is a major cause of pyrethroid resistance in insects. In this work, we evaluated the role of specific and non-specific esterases in head louse populations from Buenos Aires with different levels of resistance to permethrin. As esterase activity is substrate-dependent, four different esters were used as unspecific substrates in order to obtain a better characterization of the possible role of these enzymes in the resistance phenomenon. The unspecific substrates were phenylthioacetate, 1- and 2-naphtyl-acetate, and p-nitrophenyl acetate. A 7-coumaryl permethrate was synthesized and used as a specific substrate to measure pyrethroid esterases by a very sensitive microfluorometric method. The results on pyrethroid esterase activity obtained with this substrate showed that these enzymes contribute to the detoxifying activity in resistant populations, although no correlation was found between pyrethroid esterase activity and resistance ratios. In this study, we established that the activity of esterase against specific and non-specific substrates is increased in pyrethroid-resistant populations of head lice from Buenos Aires. Also, dichlorodiphenyltrichloroethane (DDT) resistance values demonstrated that there is a DDT cross-resistance phenomenon in pyrethroid-resistant head louse populations and suggested that an alteration in the receptor of the nervous system (kdr gen) is a key factor of the resistance phenomena in these head louse populations.