RESUMEN
BACKGROUND: The lesser grain borer, Rhyzopertha dominica is a serious pest of stored grains. Fumigation and contact insecticides play a major role in managing this pest globally. While insects are developing genetic resistance to chemicals, hormonal analogues such as s-methoprene play a key role in reducing general pest pressure as well as managing pest populations that are resistant to fumigants and neurotoxic contact insecticides. However, resistance to s-methoprene has been reported in R. dominica with some reports showing a remarkable high resistance, questioning the use of this compound and other related analogues in grain protection. The current study attempts to identify possible molecular mechanisms that contribute in resistance to s-methoprene in R. dominica. RESULTS: Transcriptome analysis of resistant and susceptible strains of this pest species identified a set of differentially expressed genes related to cytochrome P450s, indicating their potential role in resistance to s-methoprene. Laboratory bioassays were performed with s-methoprene treated wheat grains in presence and absence of piperonyl butoxide (PBO), a cytochrome P450 inhibitor. The results indicate that PBO, when applied alone, at least at the concentration tested here, had no effect on R. dominica adult emergence, but has a clear synergistic effect to s-methoprene. The number of produced progeny decreased in presence of the inhibitor, especially in the resistant strain. In addition, we also identified CYP complement (CYPome) of R. dominica, annotated and analysed phylogenetically, to understand the evolutionary relationships with other species. CONCLUSIONS: The information generated in current study suggest that PBO can effectively be used to break resistance to s-methoprene in R. dominica.
Asunto(s)
Escarabajos , Insecticidas , Animales , Escarabajos/genética , Dominica , Perfilación de la Expresión Génica , Insecticidas/farmacología , Metopreno , Butóxido de Piperonilo/farmacología , TranscriptomaRESUMEN
Bed bugs have become a common urban pest with consequences on human health and economic costs to the hotel and tourism sectors. Insecticide resistance is considered an important factor in the current bed bug resurgence, and multiple resistance mechanisms could be working in the resistant bed bug populations. In the present study, we determined the resistance profile to four insecticides with a different mode of action in Cimex lectularius L. (Heteroptera: Cimicidae) field-collected colonies from Argentina. Furthermore, the synergism effect of piperonyl butoxide (PBO) with deltamethrin was investigated to explore the contribution of detoxification metabolism to resistance. Our results showed that most of the field-collected colonies are extremely resistant to deltamethrin and propoxur, much more than to azametiphos and imidacloprid. The differences in resistance ratios among field-collected colonies could be associated with different modes of action of insecticides used in control pest and the mechanisms involved in the resistance. PBO pretreatment led to a significantly decreased RR in pyrethroid-resistant colonies, suggesting an upturn of monooxygenase activity for deltamethrin detoxification. However, the high RR detected could involve other mechanisms as part of the whole resistant phenotype in colonies of C. lectularius resistant to pyrethroids.
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Chinches/fisiología , Inhibidores Enzimáticos del Citocromo P-450/farmacología , Proteínas de Insectos/metabolismo , Resistencia a los Insecticidas , Insecticidas/farmacología , Sinergistas de Plaguicidas/farmacología , Butóxido de Piperonilo/farmacología , Animales , Argentina , Ciudades , Sistema Enzimático del Citocromo P-450/metabolismo , Femenino , Inactivación Metabólica , Masculino , Piretrinas/farmacologíaRESUMEN
The white rot basidiomycete Ganoderma lucidum was evaluated for its capability to tolerate and to degrade the herbicide diuron. Diuron at a subtoxic concentration was added at the start of the cultivation in glucose liquid stationary cultures. Under this condition diuron was a laccase inducer. Almost 50% of the initially present diuron was removed after 15 d of cultivation. Two diuron metabolites were found N'-(3,4-dichlorophenyl)-N-methylurea (DCPMU) and 3,4-dichlorophenylurea (DCPU). The addition of the cytochrome P450 inhibitors 1-aminobenzotriazole and piperonyl butoxide reduced significantly the capability of the fungus in degrading diuron. The activities of superoxide dismutase and catalase were significantly increased in the mycelial extracts by the presence of diuron. On the other hand, diuron did not cause any significant alteration in the levels of reactive oxygen species. Additionally, laccase could also degrade diuron in vitro and this degradation was increased by the addition of synthetic mediators, 3-ethylbenzthiazoline-6-sulphonic acid and acetylacetone. Significant reduction in the toxicity, as evaluated by the Lactuca sativa bioassay, was observed after G. lucidum treatment. In conclusion, G. lucidum is able to metabolize diuron by intra- and extracellular mechanisms, without the accumulation of toxic products.
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Diurona/metabolismo , Farmacorresistencia Fúngica , Herbicidas/metabolismo , Reishi/metabolismo , Biotransformación , Catalasa/metabolismo , Diurona/farmacología , Herbicidas/farmacología , Lacasa/metabolismo , Pentanonas/farmacología , Butóxido de Piperonilo/farmacología , Especies Reactivas de Oxígeno/metabolismo , Reishi/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Triazoles/farmacologíaRESUMEN
Monepantel (MNP) is a new amino-acetonitrile derivative anthelmintic drug used for the treatment of gastrointestinal (GI) nematodes in sheep. The present work investigated the main enzymatic pathways involved in the hepatic biotransformation of MNP in sheep and cattle. The metabolic stability in ruminal fluid of both the parent drug and its main metabolite (monepantel sulphone, MNPSO2 ) was characterized as well. Additionally, the relative distribution of both anthelmintic molecules between the fluid and particulate phases of the ruminal content was studied. Liver microsomal fractions from six (6) rams and five (5) steers were incubated with a 40 µm of MNP. Heat pretreatment (50 °C for 2 min) of liver microsomes was performed for inactivation of the flavin-monooxygenase (FMO) system. Additionally, MNP was incubated in the presence of 4, 40, and 80 µm of methimazole (MTZ), a FMO inhibitor, or equimolar concentrations of piperonyl butoxide (PBx), a well-known general cytochrome P450 (CYP) inhibitor. In both ruminant species, MNPSO2 was the main metabolite detected after MNP incubation with liver microsomes. The conversion rate of MNP into MNPSO2 was fivefold higher (P < 0.05) in sheep (0.15 ± 0.08 nmol/min·mg) compared to cattle. In sheep, the relative involvement of both FMO and CYP systems (FMO/CYP) was 36/64. Virtually, only the CYP system appeared to be involved in the production of MNPSO2 in cattle liver. Methimazole significantly reduced (41 to 79%) the rate of MNPSO2 production in sheep liver microsomes whereas it did not inhibit MNP oxidation in cattle liver microsomes. On the other hand, PBx inhibited the production of MNPSO2 in liver microsomes of both sheep (58 to 98%, in a dose-dependent manner) and cattle (almost 100%, independently of the PBx concentration added). The incubation of MNP and MNPSO2 with ruminal contents of both species showed a high chemical stability without evident metabolism and/or degradation as well as an extensive degree of adsorption (83% to 90%) to the solid phase of the ruminal content. Overall, these results are a further contribution to the understanding of the metabolic fate of this anthelmintic drug in ruminants.
Asunto(s)
Aminoacetonitrilo/análogos & derivados , Antihelmínticos/farmacocinética , Hígado/metabolismo , Rumen/metabolismo , Aminoacetonitrilo/farmacocinética , Animales , Biotransformación , Bovinos/metabolismo , Inhibidores Enzimáticos del Citocromo P-450/farmacología , Sistema Enzimático del Citocromo P-450/metabolismo , Relación Dosis-Respuesta a Droga , Flavinas/farmacocinética , Masculino , Metimazol/farmacología , Oxigenasas de Función Mixta/antagonistas & inhibidores , Oxigenasas de Función Mixta/metabolismo , Butóxido de Piperonilo/farmacología , Ovinos/metabolismoRESUMEN
Phytoseiulus macropilis Banks (Acari: Phytoseiidae) is an effective predator of Tetranychus urticae Koch (Acari: Tetranychidae). The objectives of this research were to study the stability of fenpropathrin resistance and the cross-resistance relationships with different pyrethroids, and also to evaluate the effect of synergists [piperonyl butoxide (PBO), diethyl maleate (DEM) and S,S,S-tributyl phosphorotrithioate (DEF)] on fenpropathrin resistant and susceptible strains of this predaceous mite. The stability of fenpropathrin resistance was studied under laboratory conditions, using P. macropilis populations with initial frequencies of 75 and 50% of resistant mites. The percentages of fenpropathrin resistant mites were evaluated monthly for a period of up to 12 months. A trend toward decreased resistance frequencies was observed only during the first 3-4 months. After this initial decrease, the fenpropathrin resistance was shown to be stable, maintaining constant resistance frequencies (around 30%) until the end of the evaluation period. Toxicity tests carried out using fenpropathrin resistant and susceptible strains of P. macropilis indicated strong positive cross-resistance between fenpropathrin and the pyrethroids bifenthrin and deltamethrin. Bioassays with the synergists DEM, DEF and PBO were also performed. The maximum synergism ratio (SR = LC50 without synergist/LC50 with synergist) detected for the three evaluated synergists (PBO, DEM, DEF) was 5.86 (for DEF), indicating low influence of enzyme detoxification processes in fenpropathrin resistance.
Asunto(s)
Acaricidas/farmacología , Ácaros/efectos de los fármacos , Nitrilos/farmacología , Piretrinas/farmacología , Animales , Resistencia a Medicamentos , Sinergismo Farmacológico , Maleatos/farmacología , Organotiofosfatos/farmacología , Butóxido de Piperonilo/farmacologíaRESUMEN
INTRODUCTION: The effects of piperonyl butoxide (PBO) on the toxicity of the organophosphate temephos (TE) and the role of esterases in the resistance of Aedes aegypti to this insecticide were evaluated. METHODS: A. aegypti L4 larvae susceptible and resistant to TE were pre-treated with PBO solutions in acetone at concentrations of 0.125, 0.25, 0.5, 1, and 2% for 24h and subsequently exposed to a diagnostic concentration of 0.02 mg/L aqueous TE solution. The esterase activity of the larvae extracts pre-treated with varying PBO concentrations and exposed to TE for three time periods was determined. RESULTS: At concentrations of 0.25, 0.5, 1, and 2%, PBO showed a significant synergistic effect with TE toxicity. High levels of esterase activity were associated with the survival of A. aegypti L4 larvae exposed to TE only. CONCLUSIONS: The results of the biochemical assays suggest that PBO has a significant inhibitory effect on the total esterase activity in A. aegypti larvae.
Asunto(s)
Aedes/efectos de los fármacos , Aedes/enzimología , Esterasas/fisiología , Resistencia a los Insecticidas , Sinergistas de Plaguicidas/farmacología , Butóxido de Piperonilo/farmacología , Temefós/toxicidad , Animales , Larva/efectos de los fármacos , OrganofosfatosRESUMEN
Introduction The effects of piperonyl butoxide (PBO) on the toxicity of the organophosphate temephos (TE) and the role of esterases in the resistance of Aedes aegypti to this insecticide were evaluated. Methods A. aegypti L4 larvae susceptible and resistant to TE were pre-treated with PBO solutions in acetone at concentrations of 0.125, 0.25, 0.5, 1, and 2% for 24h and subsequently exposed to a diagnostic concentration of 0.02mg/L aqueous TE solution. The esterase activity of the larvae extracts pre-treated with varying PBO concentrations and exposed to TE for three time periods was determined. Results At concentrations of 0.25, 0.5, 1, and 2%, PBO showed a significant synergistic effect with TE toxicity. High levels of esterase activity were associated with the survival of A. aegypti L4 larvae exposed to TE only. Conclusions The results of the biochemical assays suggest that PBO has a significant inhibitory effect on the total esterase activity in A. aegypti larvae. .
Asunto(s)
Animales , Aedes/efectos de los fármacos , Aedes/enzimología , Esterasas/fisiología , Resistencia a los Insecticidas , Sinergistas de Plaguicidas/farmacología , Butóxido de Piperonilo/farmacología , Temefós/toxicidad , Larva/efectos de los fármacos , OrganofosfatosRESUMEN
A field strain of Aedes aegypti (L.) was collected from Puerto Rico in October 2008. Based on LD50 values by topical application, the Puerto Rico strain was 73-fold resistant to permethrin compared with a susceptible Orlando strain. In the presence of piperonyl butoxide, the resistance of Puerto Rico strain of Ae. aegypti was reduced to 15-fold, suggesting that cytochrome P450-mediated detoxification is involved in the resistance of the Puerto Rico strain to permethrin. To determine the cytochrome P450s that might play a role in the resistance to permethrin, the transcriptional levels of 164 cytochrome P450 genes in the Puerto Rico strain were compared with that in the Orlando strain. Of the 164 cytochrome P450s, 33 were significantly (P < 0.05) up-regulated, including cytochrome P450s in families four, six, and nine. Multiple studies have investigated the functionality of family six and nine cytochrome P450s, therefore, we focused on the up-regulated family 4 cytochrome P450s. To determine whether up-regulation of the four cytochrome P450s had any functional role in permethrin resistance, transgenic Drosophila melanogaster Meigen lines overexpressing the four family 4 P450 genes were generated, and their ability to survive exposure to permethrin was evaluated. When exposed to 5 microg per vial permethrin, transgenic D. melanogaster expressing CYP4D24, CYP4H29, CYP4J15v1, and CYP4H33 had a survival rate of 60.0 +/- 6.7, 29.0 +/- 4.4, 64.4 +/- 9.7, and 11.0 +/- 4.4%, respectively. However, none of the control flies survived the permethrin exposure at the same concentration. Similarly, none of the transgenic D. melanogaster expressing CYP4J15v1 or CYP4H33 ?5 survived when they were exposed to permethrin at 10 microg per vial. However, transgenic D. melanogaster expressing CYP4D24 and CYP4H29 had a survival rate of 37.8 +/- 4.4 and 2.2 +/- 2.2%, respectively. Taken together, our results suggest that CYP4D24 might play an important role in cytochrome P450-mediated resistance to permethrin.
Asunto(s)
Aedes/genética , Regulación de la Expresión Génica , Resistencia a los Insecticidas , Insecticidas/farmacología , Permetrina/farmacología , Aedes/efectos de los fármacos , Aedes/metabolismo , Animales , Animales Modificados Genéticamente/genética , Animales Modificados Genéticamente/metabolismo , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Femenino , Florida , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Datos de Secuencia Molecular , Butóxido de Piperonilo/farmacología , Puerto Rico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Secuencia de ADNRESUMEN
A study was conducted to evaluate the efficacy of cypermethrin, amitraz, and piperonyl butoxide (PBO) mixtures, through in vitro laboratory bioassays and in vivo on-animal efficacy trials, for the control of resistant Rhipicephalus (Boophilus) microplus on cattle in the Mexican tropics. Also, to examine mechanisms of resistance to cypermethrin in this tick population, the frequency of a mutated sodium channel gene (F1550I) was determined using a PCR assay. Results of laboratory bioassays using modified larval packet tests revealed that cypermethrin toxicity was synergized by PBO (from 46.6-57.0% to 83.7-85.0% larval mortality; P<0.05). The cypermethrin and amitraz mixture showed an additive effect (from 46.6-57.0% to 56.0-74.3% larval mortality). Strong synergism was observed with the mixture of cypermethrin+amitraz+PBO and this mixture was the most effective killing resistant tick larvae in vitro (96.7-100% of larval mortality). Tick larvae surviving exposure to cypermethrin or mixtures either with amitraz and PBO in vitro showed 2.9-49.6 higher probability to present the mutated allele than those killed by acaricide treatment (P<0.05). In the in vivo trial, the mixtures containing cypermethrin+PBO (80.6-97.3%), and cypermethrin+amitraz (87.0-89.7%) were more efficacious than cypermethrin alone (76.3-80.5%). The highest level of efficacy was obtained with the mixture of cypermethrin+amitraz+PBO, which yielded >95% control that persisted for 28 days post-treatment against R. microplus infesting cattle when tested under field conditions in the Mexican tropics. Although this mixture is a potentially useful tool to combat pyrethroid resistance, a product based on an acaricide mixture like the one tested in this study has to be used rationally.
Asunto(s)
Resistencia a los Insecticidas , Butóxido de Piperonilo/farmacología , Piretrinas/farmacología , Rhipicephalus/efectos de los fármacos , Toluidinas/farmacología , Clima Tropical , Animales , Resistencia a los Insecticidas/genética , Insecticidas/administración & dosificación , Insecticidas/farmacología , Larva/efectos de los fármacos , México , Mutación , Sinergistas de Plaguicidas , Butóxido de Piperonilo/administración & dosificación , Piretrinas/administración & dosificación , Rhipicephalus/genética , Rhipicephalus/metabolismo , Canales de Sodio/genética , Canales de Sodio/metabolismo , Toluidinas/administración & dosificaciónRESUMEN
Essential oils (EOs) are potential tools for controlling Musca domestica L. In a fumigant assay, M. domestica adults treated with Citrus sinensis EO (LC50=3.9mg/dm(3)), with (4R)(+)-limonene (95.1%) being its main component, died within 15min or less. The terpenes absorbed by the flies and their metabolites, analyzed using SPME fiber, were (4R)(+)-limonene (LC50=6.2mg/dm(3)), α-pinene (LC50=11.5mg/dm(3)), ß-pinene (LC50=6.4mg/dm(3)), and two new components, carveol (LC50=1122mg/dm(3)) and carvone (LC50=19mg/dm(3)), in a proportion of 50, 6.2, 12.5, 6.3 and 25%, respectively. Carveol and carvone were formed by oxidation of (4R)(+)-limonene mediated by cytochrome P450, as was suggested by a fumigation assay on flies previously treated with piperonyl butoxide, a P450 inhibitor. In this experiment, an increase in the toxicity of the EO and (4R)(+)-limonene was observed, as well as a lower production of carveol and carvone.
Asunto(s)
Citrus sinensis/química , Moscas Domésticas/efectos de los fármacos , Insecticidas/farmacología , Aceites Volátiles/farmacología , Butóxido de Piperonilo/farmacología , Aceites de Plantas/farmacología , Animales , Inhibidores Enzimáticos del Citocromo P-450 , Femenino , Insecticidas/química , Masculino , Estructura Molecular , Aceites Volátiles/química , Butóxido de Piperonilo/química , Aceites de Plantas/química , Terpenos/química , Terpenos/metabolismo , Terpenos/farmacologíaRESUMEN
The effect of exposing Triatoma infestans to chickens treated with cypermethrin pour-on combined with piperonyl butoxide (PBO) was studied. Four groups of treated chickens and one control group were used. Each treatment received 1 or 2 ml of the cypermethrin formulation with and without PBO. Independent groups of nymphs were fed 1, 7, 15, 30, and 45 d after the treatment application. Blood intake was estimated after each feeding occasion. Up to 15 d after the pour-on application, high mortality was observed in all nymphs fed on treated chickens (> 93% +/- 12), and lower than the nymphs of the control group (< 33% +/- 15). After 30 d of the pour-on application, there was significantly different mortality between the treatment with 1 ml (80% +/- 9) and 2 ml (> 96% +/- 5); no difference was observed between groups with or without PBO addition. After 45 d of the pour-on application, the treatments did not show significant differences (77% +/- 7), although all treatments showed higher mortality than the control group (10% +/- 9). Up to 45 d after the pour-on application, blood intake by nymphs exposed to treated chickens (0.85 +/- 0.96 mg/nymph) was lower than blood intake by nymphs exposed to control chickens (6.7 +/- 5 mg/nymph). This study shows that cypermethrin pour-on produces high mortality and reduces the blood intake of third-instar nymphs of T. infestans up to 45 d after the insecticide application to chickens. PBO did not produce a detectable effect.
Asunto(s)
Pollos , Butóxido de Piperonilo/farmacología , Piretrinas/farmacología , Triatoma/efectos de los fármacos , Administración Tópica , Animales , Quimioterapia Combinada , Mordeduras y Picaduras de Insectos/prevención & control , Muda , Ninfa/efectos de los fármacos , Ninfa/fisiología , Butóxido de Piperonilo/administración & dosificación , Piretrinas/administración & dosificación , Triatoma/fisiologíaRESUMEN
Understanding the disposition kinetics and the pattern of metabolism is critical to optimise the flukicidal activity of triclabendazole (TCBZ) in ruminants. TCBZ is metabolised by both flavin-monooxygenase (FMO) and cytochrome P450 (P450) in the liver. Interference with these metabolic pathways may be useful to increase the systemic availabilities of TCBZ metabolites, which may improve the efficacy against Fasciola hepatica. The plasma disposition of TCBZ metabolites was evaluated following TCBZ co-administration with FMO [methimazole (MTZ)] and P450 [piperonyl butoxyde (PB) and ketoconazole (KTZ)] inhibitors in sheep. Twenty (20) healthy Corriedale x Merino weaned female lambs were randomly allocated into four experimental groups. Animals of each group were treated as follow: Group A, TCBZ alone (5 mg/kg, IV route); Group B, TCBZ (5 mg/kg, IV) + MTZ (3 mg/kg, IV); Group C, TCBZ (5 mg/kg, IV) + PB (30 mg/kg, IV) and Group D, TCBZ (5 mg/kg, IV) + KTZ (10 mg/kg, orally). Blood samples were taken over 240 h post-treatment and analysed by HPLC. TCBZ sulphoxide and sulphone were the main metabolites recovered in plasma. MTZ did not affect TCBZ disposition kinetics. TCBZ sulphoxide Cmax values were significantly increased (P < 0.05) after the TCBZ + PB (62%) and TCBZ + KTZ (37%) treatments compared to those measured in the TCBZ alone treatment. TCBZ sulphoxide plasma AUCs were higher (P < 0.05) in the presence of both PB (99%) and KTZ (41%). Inhibition of TCBZ P450-mediated oxidation in the liver accounted for the increased systemic availability of its active metabolite TCBZ sulphoxide. This work contributes to the search of different strategies to improve the use of this flukicidal drug in ruminants.
Asunto(s)
Antihelmínticos/farmacocinética , Bencimidazoles/farmacocinética , Inhibidores Enzimáticos del Citocromo P-450 , Ovinos/metabolismo , Animales , Animales Recién Nacidos , Antihelmínticos/sangre , Área Bajo la Curva , Bencimidazoles/sangre , Disponibilidad Biológica , Cromatografía Líquida de Alta Presión/métodos , Cromatografía Líquida de Alta Presión/veterinaria , Femenino , Cetoconazol/farmacología , Metimazol/farmacología , Butóxido de Piperonilo/farmacología , Distribución Aleatoria , Ovinos/sangre , TriclabendazolRESUMEN
Mixed populations of the pest blackflies Simulium bonaerense Coscarón & Wygodzinsky, S. wolffhuegeli (Enderlein) and S. nigristrigatum Wygodzinsky & Coscarón (Diptera: Simuliidae) are highly resistant to DDT and pyrethroids in the Neuquén Valley, a fruit-growing area of northern Patagonia, Argentina. As these insecticides have not been used for blackfly control, resistance is attributed to exposure to agricultural insecticides. Pre-treatment with the synergist piperonyl butoxide (PBO) reduced both DDT and fenvalerate resistance, indicating that resistance was partly due to monooxygenase inhibition. Pre-treatment with the synergist tribufos to inhibit esterases slightly increased fenvalerate toxicity in the resistant population. Even so, biochemical studies indicated almost three-fold higher esterase activity in the resistant population, compared to the susceptible. Starch gel electrophoresis confirmed higher frequency and staining intensity of esterase electromorphs in the resistant population. Incomplete synergism against metabolic resistance indicates additional involvement of a non-metabolic resistance mechanism, such as target site insensitivity, assumed to be kdr-like in this case. Glutathione S-transferase activities were low and inconsistent, indicating no role in Simulium resistance. Knowing these spectra of insecticide activity and resistance mechanisms facilitates the choice of more effective products for Simulium control and permits better coordination with agrochemical operations.
Asunto(s)
DDT/farmacología , Resistencia a los Insecticidas , Insecticidas/farmacología , Piretrinas/farmacología , Simuliidae/efectos de los fármacos , Animales , Argentina , Esterasas/metabolismo , Larva/efectos de los fármacos , Dosificación Letal Mediana , Nitrilos , Sinergistas de Plaguicidas/farmacología , Butóxido de Piperonilo/farmacología , Simuliidae/enzimologíaRESUMEN
Effects of the synergists piperonyl butoxide (PBO) and S,S,S-tributyl phosphorotrithioate (DEF) on propoxur pharmacokinetics were examined in the German cockroach, Blattella germanica (L.). Treatment of adult male German cockroaches with the cytochrome P450 monooxygenase inhibitor, PBO, or the esterase inhibitor, DEF, increased propoxur toxicity by 2- and 6.8-fold, respectively, implicating hydrolysis as a major detoxification route of propoxur in the German cockroach. However, significant hydrolytic metabolism could not be demonstrated conclusively in vitro resulting in a conflict between in situ bioassay data and in vitro metabolic studies. In vitro propoxur metabolism with NADPH-fortified microsomes produced at least nine metabolites. Formation of metabolites was NADPH-dependent; no quantifiable metabolism was detected with cytosolic fractions. However, microsomal fractions lacking an NADPH source did produce a low, but detectable, quantity of metabolites (1.6 pmol). PBO inhibited NADPH-dependent propoxur metabolism in a dose-dependent fashion, implicating cytochrome P450 monooxygenases as the enzyme system responsible for the metabolism. Interestingly, DEF also inhibited the NADPH-dependent metabolism of propoxur, albeit to a lower extent. Treatment with PBO or DEF also caused a significant reduction in the cuticular penetration rate of propoxur. The data demonstrate that unanticipated effects are possible with synergists and that caution must be exercised when interpreting synergist results.
Asunto(s)
Blattellidae/metabolismo , Inhibidores Enzimáticos/farmacología , Control de Insectos , Insecticidas/farmacocinética , Organotiofosfatos/farmacología , Sinergistas de Plaguicidas/farmacología , Butóxido de Piperonilo/farmacología , Propoxur/farmacocinética , Animales , Blattellidae/efectos de los fármacos , Inhibidores Enzimáticos del Citocromo P-450 , Esterasas/antagonistas & inhibidores , Control de Insectos/métodos , Insecticidas/metabolismo , Masculino , Sinergistas de Plaguicidas/metabolismo , Butóxido de Piperonilo/metabolismo , Propoxur/metabolismoRESUMEN
Resistance levels to insecticides used in control of Chagas Disease vectors were assessed in two species of bugs (Hemiptera: Reduviidae): Triatoma infestans (Klug) from Brazil and Rhodnius prolixus Stål from Venezuela. The resistance ratios, compared to susceptible laboratory strains, were determined by topical application bioassays. The T. infestans PA strain exhibited resistance ratios of 7x to deltamethrin, 3.6x to beta-cyfluthrin and 3.3x to cypermethrin, but was susceptible to beta-cypermethrin and lambda-cyhalothrin. Rhodnius prolixus CA strain showed resistance to all the pyrethroids evaluated, the resistance ratios ranging between 4.5x to lambda-cyhalothrin and 12.4x to cypermethrin. Deltamethrin resistance in both strains was decreased by piperonyl butoxide, suggesting oxidative metabolism as cause of resistance.
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Resistencia a los Insecticidas , Insecticidas/farmacología , Plantas , Piretrinas , Rhodnius , Triatoma , Administración Tópica , Animales , Brasil , Dieldrín/administración & dosificación , Dieldrín/farmacología , Sinergismo Farmacológico , Insecticidas/administración & dosificación , Butóxido de Piperonilo/administración & dosificación , Butóxido de Piperonilo/farmacología , Trypanosoma cruzi , VenezuelaRESUMEN
Development of pyrethroid resistance in Haematobia irritans in Santa Fe province, Argentina, resulted in an increased use of pyrethroid insecticides, probably due to lack of suitable alternative treatments. We explored the efficacy of mixtures of cypermethrin and piperonyl butoxide (PBO) against pyrethroid-resistant H. irritans. Groups of 25 Holstein cows each, naturally infested with cypermethrin resistant H. irritans were assigned to treated or control groups in April, September, October and December 1997. Cattle in treated groups were medicated with pour-on oil formulations of 5% cypermethrin (dose = 4 mg per kg of body weight) with 5% or 10% PBO in April, and with a mixture containing 5% of both components thereafter. Efficacy was tested for 21 days after treatment. A treatment of 5% cypermethrin pour-on without PBO was evaluated in October 1997. Samples of horn flies were obtained before September, October and December treatments and exposed for 2 h to filter papers impregnated with different cypermethrin concentrations to determine the 50% lethal concentration (LC50). No difference in efficacy was found between cypermethrin pour-on formulations with 5% or 10% of PBO (more than 94% efficacy on day 21 after treatment). Efficacy of 5 % cypermethrin-5% PBO mixture decreased rapidly in the successive treatments (less than 40% efficacy was observed on day 21 after the December treatment), and the period after treatment with an efficacy higher than 95% was 14 days for the treatment carried out in April, 10 days in September; 7 days for the treatment performed in October and 4 days for the December treatment. The LC50 of cypermethrin was 36.6 microg per cm2 in September and increased to 116.6 and 226.1 microg per cm2 in October and December, respectively. It is concluded that the addition of PBO to cypermethrin did not provide a treatment that would give a long term control of pyrethroid resistant-horn flies.