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1.
Vet Parasitol ; 273: 105-111, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31473449

RESUMO

Diclazuril, which is widely used for the prevention of coccidiosis in chickens, has a lethal effect on asexual and sexual stages of Eimeria spp. However, little is known about its effect on the exogenous stages of Eimeria spp. In this study, we evaluated the effect of in vitro treatment with 0.2% diclazuril on unsporulated and sporulated oocysts of Eimeria spp. For this purpose, a total of 180 male layer chicks aged one day were randomly divided into 5 experimental groups. Each group was divided into 3 replicates of 12 chicks each. Group 1 (G1) and Group 2 (G2) were negative (non-immunized and non-challenged) and positive (non-immunized and challenged) controls, respectively. Group 3 (G3) was immunized per os with 1.0 × 104 non-diclazuril treated-sporulated oocysts. Groups 4 (G4) was immunized per os with 0.2% diclazuril treated-unsporulated oocysts (1.0 × 104) in which diclazzuril didn't affect sporulation. Group 5 (G5) was immunized per os with 0.2% diclazuril treated-sporulated oocysts (1.0 × 104). Chicks of G2, G3, G4, and G5 were challenged with 7.5 × 104 untreated sporulated oocysts at the age of 21 days, while the group 1 chicks remained unchallenged. G4 and G5 animals immunized with 0.2% diclazuril-treated oocysts showed a significant decrease in bloody diarrhea severity, lesion scores, and oocyst counts in comparison to those immunized with untreated oocysts. Furthermore, histopathologic findings showed a low number of parasitic stages in cecal tissues in G4 and G5. A significant increased body weight gain was observed in Gs 4 and 5 in comparison to G2. In addition, expression levels of IL-2, IL-12, and IFN-γ were significantly increased in G4 and G5. In conclusion, diclazuril is effective in attenuating Eimeria oocysts and thus provides an alternative approach for using diclazuril-treated oocysts to protect chicks against Eimeria challenge.


Assuntos
Coccidiose/veterinária , Eimeria/efeitos dos fármacos , Nitrilos/farmacologia , Oocistos/efeitos dos fármacos , Doenças das Aves Domésticas , Triazinas/farmacologia , Animais , Ceco/parasitologia , Galinhas , Coccidiose/parasitologia , Coccidiose/prevenção & controle , Eimeria/patogenicidade , Masculino , Doenças das Aves Domésticas/parasitologia , Doenças das Aves Domésticas/prevenção & controle , Distribuição Aleatória , Virulência/efeitos dos fármacos
2.
Chem Biol Interact ; 311: 108796, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31421116

RESUMO

Lambda-cyhalothrin (LCT) is a broad-spectrum pesticide widely used in agriculture throughout the world. This pesticide is considered a potential contaminant of surface and underground water as well as food, posing a risk to ecosystems and humans. In this sense, we decided to evaluate the activity of enzymes belonging to the purinergic system, which is linked with regulation of extracellular nucleotides and nucleosides, such as adenosine triphosphate (ATP) and adenosine (Ado) molecules involved in the regulation of inflammatory response. However, there are no data concerning the effects of LCT exposure on the purinergic system, where extracellular nucleotides act as signaling molecules. The aim of this study was to evaluate nucleotide hydrolysis by E-NTPDase (ecto-nucleoside triphosphate diphosphohydrolase), Ecto-NPP (ecto-nucleotide pyrophosphatase/phosphodiesterase), ecto-5'-nucleotidase and ecto-adenosine deaminase (E-ADA) in platelets and liver of adult rats on days 7, 30, 45 and 60 after daily gavage with 6.2 and 31.1 mg/kg bw of LCT. Gene expression patterns of NTPDases1-3 and 5'-nucleotidase were also determined in those tissues. In parallel, lambda-cyhalothrin metabolites [3-(2-chloro-3,3,3- trifluoroprop-1-enyl)-2,2-dimethyl-cyclopropane carboxylic acid (CFMP), 4-hydroxyphenoxybenzoic acid (4-OH-3-PBA), and 3-phenoxybenzoic acid (3-PBA)] were measured in plasma. Results showed that exposure rats to LCT caused a significant increase in the assessed enzymes activities. Gene expression pattern of ectonucleotidases further revealed a significant increase in E-NTPDase1, E-NTPDase2, and E-NTPDase3 mRNA levels after LCT administration at all times. A dose-dependent increase in LCT metabolite levels was also observed but there no significant variations in levels from weeks to week, suggesting steady-steady equilibrium. Correlation analyses revealed that LCT metabolites in the liver and plasma were positively correlated with the adenine nucleotides hydrolyzing enzyme, E-ADA and E-NPP activities in platelets and liver of rats exposed to lambda-cyhalothin. Our results show that LCT and its metabolites may affect purinergic enzymatic cascade and cause alterations in energy metabolism.


Assuntos
Plaquetas/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Nitrilos/farmacologia , Nucleotidases/genética , Nucleosídeos de Purina/metabolismo , Piretrinas/farmacologia , Adenosina Desaminase/genética , Adenosina Desaminase/metabolismo , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Animais , Plaquetas/enzimologia , Plaquetas/metabolismo , Cromatografia Líquida de Alta Pressão , Hidrólise , Fígado/enzimologia , Fígado/metabolismo , Masculino , Espectrometria de Massas , Nitrilos/sangue , Nitrilos/metabolismo , Nucleotidases/metabolismo , Piretrinas/sangue , Piretrinas/metabolismo , Pirofosfatases/genética , Pirofosfatases/metabolismo , Ratos , Ratos Wistar
3.
Pestic Biochem Physiol ; 158: 143-148, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31378350

RESUMO

Chinese sprangletop (Leptochloa chinensis (L.) Nees) is one of the most troublesome grass weeds in rice in China. Seven suspected cyhalofop-butyl-resistant L. chinensis populations were collected from different rice fields with a history of cyhalofop-butyl use. The level of resistance and resistance mechanisms in seven populations were studied. Dose-response tests indicated that five populations (JS3, JS4, JS6, JS7 and JS8) had evolved high-level resistance (26.9 to 123.0-fold) to cyhalofop-butyl compared with the susceptible (S) population, and other two populations (JS2 and JS5) were still sensitive to the herbicide. Two acetyl-coenzyme A carboxylase (ACCase) genes were cloned from each population, and three different ACCase mutations (Ile-1781-Leu, Trp-1999-Cys, and Trp-2027-Cys) in ACCase2 gene were determined in different resistant (R) populations. In addition, no resistance-conferring mutations was detected in the R population (JS7), and ACCase gene expression was similar between the S and R populations. Thus, non-target-site resistance mechanisms may be involved in the JS7 population. Moreover, the patterns of cross-resistance of JS6 (Ile-1781-Leu), JS4 (Trp-1999-Cys), JS8 (Trp-2027-Cys), and JS7 (unknown resistance mechanisms) populations to other ACCase-inhibiting herbicides were determined. The JS6 and JS8 populations showed resistance to fenoxaprop-P-ethyl, metamifop, clethodim and pinoxaden, the JS4 population was resistant to fenoxaprop-P-ethyl, metamifop and pinoxaden, and the JS7 population had resistance only to fenoxaprop-P-ethyl and metamifop. These results indicated the diversity of the target-site mutations in ACCase gene of L. chinensis, and provide a better understanding of cross-resistance in L. chinensis, which would be helpful for the management of cyhalofop-butyl-resistant L. chinensis.


Assuntos
Acetil-CoA Carboxilase/metabolismo , Butanos/farmacologia , Herbicidas/farmacologia , Nitrilos/farmacologia , Poaceae/metabolismo , Acetil-CoA Carboxilase/genética , China , Resistência a Herbicidas/genética , Poaceae/efeitos dos fármacos
4.
Parasit Vectors ; 12(1): 337, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31287014

RESUMO

BACKGROUND: Aedes aegypti were found developing in the water in open public drains (drain-water, DW) in Jaffna city in northern Sri Lanka, a location where the arboviral diseases dengue and chikungunya are endemic. METHODS: Susceptibilities to the common insecticides dichlorodiphenyltrichloroethane (DDT), malathion, propoxur, permethrin and deltamethrin and activities of the insecticide-detoxifying enzymes carboxylesterase (EST), glutathione S-transferase (GST) and monooxygenase (MO) were compared in adult Ae. aegypti developing in DW and fresh water (FW). RESULTS: DW Ae. aegypti were resistant to the pyrethroids deltamethrin and permethrin, while FW Ae. aegypti were susceptible to deltamethrin but possibly resistant to permethrin. Both DW and FW Ae. aegypti were resistant to DDT, malathion and propoxur. Greater pyrethroid resistance in DW Ae. aegypti was consistent with higher GST and MO activities. CONCLUSIONS: The results demonstrate the potential for insecticide resistance developing in Ae. aegypti adapted to DW. Urbanization in arboviral disease-endemic countries is characterized by a proliferation of open water drains and therefore the findings identify a potential new challenge to global health.


Assuntos
Aedes/enzimologia , Arbovirus/fisiologia , Resistência a Inseticidas , Mosquitos Vetores/enzimologia , Águas Residuárias/parasitologia , Aedes/efeitos dos fármacos , Aedes/virologia , Animais , Carboxilesterase/metabolismo , DDT/farmacologia , Feminino , Saúde Global , Glutationa Transferase/metabolismo , Humanos , Inseticidas/farmacologia , Malation/farmacologia , Masculino , Camundongos , Oxigenases de Função Mista/metabolismo , Mosquitos Vetores/efeitos dos fármacos , Mosquitos Vetores/virologia , Nitrilos/farmacologia , Permetrina/farmacologia , Propoxur/farmacologia , Piretrinas/farmacologia
5.
Cytogenet Genome Res ; 158(1): 17-24, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31261155

RESUMO

Osteoarthritis (OA) is a degenerative disease characterized by progressive articular cartilage destruction and joint marginal osteophyte formation with different degrees of synovitis. Docosahexaenoic acid (DHA) is an unsaturated fatty acid with anti-inflammatory, antioxidant, and antiapoptotic functions. In this study, the human chondrosarcoma cell line SW1353 was cultured in vitro, and an OA cell model was constructed with inflammatory factor IL-1ß stimulation. After cells were treated with DHA, cell apoptosis was measured. Western blot assay was used to detect protein expression of apoptosis-related factors (Bax, Bcl-2, and cleaved caspase-3) and mitogen-activated protein kinase (MAPK) signaling pathway family members, including extracellular signal-regulated kinase (ERK), c-JUN N-terminal kinase (JNK), and p38 MAPK. Our results show that IL-1ß promotes the apoptosis of SW1353 cells, increases the expression of Bax and cleaved caspase-3, and activates the MAPK signaling pathway. In contrast, DHA inhibits the expression of IL-1ß, inhibits IL-1ß-induced cell apoptosis, and has a certain inhibitory effect on the activation of the MAPK signaling pathway. When the MAPK signaling pathway is inhibited by its inhibitors, the effects of DHA on SW1353 cells are weakened. Thus, DHA enhances the apoptosis of SW1353 cells through the MAPK signaling pathway.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias Ósseas/patologia , Condrossarcoma/patologia , Ácidos Docosa-Hexaenoicos/farmacologia , Interleucina-1beta/antagonistas & inibidores , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Osteoartrite/tratamento farmacológico , Proteínas Reguladoras de Apoptose/biossíntese , Proteínas Reguladoras de Apoptose/genética , Butadienos/farmacologia , Linhagem Celular Tumoral , Avaliação Pré-Clínica de Medicamentos , Ativação Enzimática/efeitos dos fármacos , Indução Enzimática/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-1beta/biossíntese , Interleucina-1beta/genética , Interleucina-1beta/farmacologia , Sistema de Sinalização das MAP Quinases/fisiologia , Proteínas Quinases Ativadas por Mitógeno/biossíntese , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Nitrilos/farmacologia , Inibidores de Proteínas Quinases/farmacologia
6.
Chem Pharm Bull (Tokyo) ; 67(7): 699-706, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31257325

RESUMO

In our search for novel orally active α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists, we found that conversion of an allyl group in the lead compound 2-[allyl(4-methylphenyl)amino]-4H-pyrido[3,2-e][1,3]thiazin-4-one (4) to a 2-cyanoethyl group significantly increased inhibitory activity against AMPA receptor-mediated kainate-induced toxicity in rat hippocampal cultures. Here, we synthesized 10 analogs bearing a 2-cyanoethyl group and administered them to mice to evaluate their anticonvulsant activity in maximal electroshock (MES)- and pentylenetetrazol (PTZ)-induced seizure tests, and their effects on motor coordination in a rotarod test. 3-{(4-Oxo-4H-pyrido[3,2-e][1,3]thiazin-2-yl)[4-(trifluoromethoxy)phenyl]amino}propanenitrile (25) and 3-[(2,2-difluoro-2H-1,3-benzodioxol-5-yl)(4-oxo-4H-pyrido[3,2-e][1,3]thiazin-2-yl)amino]propanenitrile (27) exhibited potent anticonvulsant activity in both seizure tests and induced minor motor disturbances as indicated in the rotarod test. The protective index values of 25 and 27 for MES-induced seizures (10.7 and 12.0, respectively) and PTZ-induced seizures (6.0 and 5.6, respectively) were considerably higher compared with those of YM928 (5) and talampanel (1).


Assuntos
Anticonvulsivantes/síntese química , Nitrilos/química , Receptores de AMPA/antagonistas & inibidores , Administração Oral , Animais , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Microssomos Hepáticos/metabolismo , Nitrilos/farmacologia , Nitrilos/uso terapêutico , Pentilenotetrazol/toxicidade , Ratos , Ratos Wistar , Receptores de AMPA/metabolismo , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Convulsões/veterinária , Relação Estrutura-Atividade
7.
Pestic Biochem Physiol ; 157: 1-12, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31153457

RESUMO

The use of neurotoxic chemical insecticides has led to consequences against the environment, insect resistances and side-effects on non-target organisms. In this context, we developed a novel strategy to optimize insecticide efficacy while reducing doses. It is based on nanoencapsulation of a pyrethroid insecticide, deltamethrin, used as synergistic agent, combined with a non-encapsulated oxadiazine (indoxacarb). In this case, the synergistic agent is used to increase insecticide efficacy by activation of calcium-dependant intracellular signaling pathways involved in the regulation of the membrane target of insecticides. In contrast to permethrin (pyrethroid type I), we report that deltamethrin (pyrethroid type II) produces an increase in intracellular calcium concentration in insect neurons through the reverse Na/Ca exchanger. The resulting intracellular calcium rise rendered voltage-gated sodium channels more sensitive to lower concentration of the indoxacarb metabolite DCJW. Based on these findings, in vivo studies were performed on the cockroach Periplaneta americana and mortality rates were measured at 24 h, 48 h and 72 h after treatments. Comparative studies of the toxicity between indoxacarb alone and indoxacarb combined with deltamethrin or nanoencapsulated deltamethrin (LNC-deltamethrin), indicated that LNC-deltamethrin potentiated the effect of indoxacarb. We also demonstrated that nanoencapsulation protected deltamethrin from esterase-induced enzymatic degradation and led to optimize indoxacarb efficacy while reducing doses. Moreover, our results clearly showed the benefit of using LNC-deltamethrin rather than piperonyl butoxide and deltamethrin in combination commonly used in formulation. This innovative strategy offers promise for increasing insecticide efficacy while reducing both doses and side effects on non-target organisms.


Assuntos
Cálcio/metabolismo , Inseticidas/química , Inseticidas/farmacologia , Nanocápsulas/química , Nitrilos/química , Nitrilos/farmacologia , Oxazinas/química , Oxazinas/farmacologia , Piretrinas/química , Piretrinas/farmacologia , Animais , Células Cultivadas , Baratas , Masculino , Estrutura Molecular , Periplaneta/efeitos dos fármacos , Trocador de Sódio e Cálcio/metabolismo
8.
Pestic Biochem Physiol ; 157: 196-203, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31153469

RESUMO

Overexpression of the cytochrome P450 monooxygenase CYP6A51 has been previously associated with pyrethroid resistance in the Mediterranean fruit fly (medfly) Ceratitis capitata, an important pest species worldwide; however, this association has not been functionally validated. We expressed CYP6A51 gene in Escherichia coli and produced a functional enzyme with preference for the chemiluminescent substrate Luciferin-ME EGE. In vitro metabolism assays revealed that CYP6A51 is capable of metabolizing two insecticides that share the same mode of action, λ-cyhalothrin and deltamethrin, whereas no metabolism or substrate depletion was observed in the presence of spinosad or malathion. We further expressed CYP6A51 in vivo via a GAL4/UAS system in Drosophila melanogaster flies, driving expression with detoxification tissue-specific drivers. Toxicity bioassays indicated that CYP6A51 confers knock-down resistance to both λ-cyhalothrin and deltamethrin. Detection of CYP6A51 - associated pyrethroid resistance in field populations may be important for efficient Insecticide Resistance Management (IRM) strategies.


Assuntos
Ceratitis capitata/efeitos dos fármacos , Ceratitis capitata/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Piretrinas/farmacologia , Animais , Sistema Enzimático do Citocromo P-450/genética , Família 6 do Citocromo P450/genética , Família 6 do Citocromo P450/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Inseticidas/farmacologia , Nitrilos/farmacologia
9.
Pestic Biochem Physiol ; 157: 69-79, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31153479

RESUMO

Carboxylesterases (CarEs) are a major class of detoxification enzymes involved in insecticide resistance in various insect species. In this study, a novel CarE 001G was isolated from the cotton bollworm Helicoverpa armigera, one of the most destructive agricultural insect pests. The open reading frame of 001G has 2244 nucleotides and putatively encodes 747 amino acid residues. The deduced CarE possessed the highly conserved catalytic triads(Ser-Glu-His) and pentapeptide motifs (Gly-X-Ser-X-Gly), suggesting 001G is biologically active. The truncated 001G was successfully expressed in Escherichia coli, and the recombinant proteins were purified and tested. The enzyme kinetic assay showed the purified proteins could catalyze two model substrates, α-naphthyl acetate and ß-naphthyl acetate, with a kcat of 8.8 and 2.3 s-1, a Km of 9.6 and 16.2 µM, respectively. The inhibition study with pyrethroid, organophosphate and neonicotinoid insecticides showed different inhibition profile against the purified CarE. The HPLC assay demonstrated that the purified proteins were able to metabolize ß-cypermethrin, λ-cyhalothrin and fenvalerate insecticides, exhibiting respective specific activities of 1.7, 1.4 and 0.5 nM/min/mg protein. However, the purified proteins were not able to metabolize the chlorpyrifos, parathion-methyl, paraoxon-ethyl and imidacloprid. The modeling and docking analyses consistently demonstrated that the pyrethroid molecule fits snugly into the catalytic pocket of the CarE 001G. Collectively, our results suggest that 001G may play a role in pyrethroids detoxification in H. armigera.


Assuntos
Carboxilesterase/metabolismo , Inseticidas/metabolismo , Inseticidas/farmacologia , Mariposas/enzimologia , Mariposas/metabolismo , Animais , Carboxilesterase/genética , Mariposas/efeitos dos fármacos , Nitrilos/metabolismo , Nitrilos/farmacologia , Piretrinas/metabolismo , Piretrinas/farmacologia
10.
Chem Pharm Bull (Tokyo) ; 67(5): 410-418, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31061365

RESUMO

2,4,5-Trichloro-6-((2,4,6-trichlorophenyl)amino)isophthalonitrile (SYD007) is a small molecule compound that was synthesized according to the structure of diarylamine. In this study, we evaluated the anti-bladder activities of SYD007, and determined its cytotoxic mechanism. We found that SYD007 exerted cytotoxicity to bladder cancer cells. Furthermore, SYD007 induced bladder cancer cell early apoptosis and arrested cell cycle. Mechanistically, SYD007 suppressed phosphorylated signal transducer and activator of transcription 3 (p-STAT3) (Tyr705) level in parallel with increases of p-extracellular signal-regulated kinase (ERK) and p-AKT. SYD007 significantly inhibited insulin-like growth factor 1 (IGF-1)-induced STAT3 activation through down-regulation of total IGF-1R level. No dramatic changes in IGF-1R mRNA levels were observed in SYD007-treated cells, suggesting that SYD007 acted primarily at a posttranscriptional level. Using molecular docking analysis, SYD007 was identified as an IGF-1R inhibitor. In summary, we reported that SYD007 exerted anti-bladder activities, and these effects were partially due to inhibition of IGF-1R/STAT3 signaling.


Assuntos
Antineoplásicos/farmacologia , Nitrilos/farmacologia , Receptor IGF Tipo 1/antagonistas & inibidores , Receptores de Somatomedina/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Bexiga Urinária/efeitos dos fármacos , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Simulação de Acoplamento Molecular , Nitrilos/síntese química , Nitrilos/química , Receptor IGF Tipo 1/metabolismo , Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/metabolismo
11.
Mem Inst Oswaldo Cruz ; 114: e180544, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31038548

RESUMO

BACKGROUND: Aedes aegypti populations in Brazil have been subjected to insecticide selection pressures with variable levels and sources since 1967. Therefore, the Brazilian Ministry of Health (MoH) coordinated the activities of an Ae. aegypti insecticide resistance monitoring network (MoReNAa) from 1999 to 2012. OBJECTIVES: The objective of this study was to consolidate all information available from between 1985 and 2017 regarding the resistance status and mechanisms of Brazilian Ae. aegypti populations against the main insecticide compounds used at the national level, including the larvicide temephos (an organophosphate) and the adulticide deltamethrin (a pyrethroid). METHODS: Data were gathered from two sources: a bibliographic review of studies published from 1985 to 2017, and unpublished data produced by our team within the MoReNAa between 1998 and 2012. A total of 146 municipalities were included, many of which were evaluated several times, totalling 457 evaluations for temephos and 274 for deltamethrin. Insecticide resistance data from the five Brazilian regions were examined separately using annual records of both the MoH supply of insecticides to each state and the dengue incidence in each evaluated municipality. FINDINGS: Ae. aegypti resistance to temephos and deltamethrin, the main larvicide and adulticide, respectively, employed against mosquitoes in Brazil for a long time, was found to be widespread in the country, although with some regional variations. Comparisons between metabolic and target-site resistance mechanisms showed that one or another of these was the main component of pesticide resistance in each studied population. MAIN CONCLUSIONS: (i) A robust dataset on the assessments of the insecticide resistance of Brazilian Ae. aegypti populations performed since 1985 was made available through our study. (ii) Our findings call into question the efficacy of chemical control as the sole methodology of vector control. (iii) It is necessary to ensure that sustainable insecticide resistance monitoring is maintained as a key component of integrated vector management. (iv) Consideration of additional parameters, beyond the supply of insecticides distributed by the MoH or the diverse local dynamics of dengue incidence, is necessary to find consistent correlations with heterogeneous vector resistance profiles.


Assuntos
Aedes/efeitos dos fármacos , Dengue/prevenção & controle , Resistência a Inseticidas/efeitos dos fármacos , Inseticidas/farmacologia , Mosquitos Vetores/efeitos dos fármacos , Nitrilos/farmacologia , Piretrinas/farmacologia , Temefós/farmacologia , Animais , Bioensaio , Brasil/epidemiologia , Dengue/epidemiologia , Dengue/transmissão , Incidência , Inseticidas/administração & dosagem , Nitrilos/administração & dosagem , Piretrinas/administração & dosagem , Temefós/administração & dosagem
12.
Acta Trop ; 196: 7-14, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31054918

RESUMO

Triatoma infestans (Klug, 1834) is the main vector of the Chagas´ disease in Argentina. The presence of insects in the domestic environment after application of pyrethroid insecticides was reported. The colonization and the evolution of insecticide resistance are processes that can explain these control failures. In both processes, the active dispersal of insects is a determining factor. The aim of the present study was to determine whether the reproductive state modulate the dispersal capacity of females of T. infestans susceptible and resistant to deltamethrin. For this, different variables associated with active dispersal were measured in virgin and copulated females both susceptible and resistant to deltamethrin. The experimental arena was 10 m long and contained two shelters. Groups of 12 females of each experimental group were released in one of the shelters and were able to move during 3 days/nights. The results showed that the females mainly dispersed by walking regardless of the reproductive state and the toxicological phenotype. On the other hand, the copula affected the posterior dispersal capacity in females susceptible and resistant to deltamethrin. The copulated females dispersed more times, leaved more times from the shelters and showed a higher proportion of dispersed individuals than the virgin females. Finally, the insecticide resistance reduced the dispersal capacity of females. The resistant insects showed lower number of dispersal events, a lower proportion of dispersed individuals, and lower exit and entry events from/to shelter than susceptible insects. This is the first report of the effect of copula on the capacity of active dispersion in vectors of Chagas disease susceptible and resistant to insecticides.


Assuntos
Resistência a Inseticidas , Nitrilos/farmacologia , Piretrinas/farmacologia , Triatoma/efeitos dos fármacos , Triatoma/fisiologia , Animais , Argentina/epidemiologia , Doença de Chagas/epidemiologia , Doença de Chagas/transmissão , Feminino , Inseticidas/farmacologia , Reprodução/efeitos dos fármacos , Triatoma/genética
13.
Acta Trop ; 196: 42-47, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31077641

RESUMO

Over the past decade, insecticide resistance to malaria vectors has been identified in 71 malaria endemic countries. This has posed a major global health challenge in the fight against malaria, with declining rates of indoor residual spraying coverage attributed to pyrethroid-resistance. As part of its vector control monitoring strategies, the Bioko Island Malaria Control Project (BIMCP) in Equatorial Guinea conducted routine insecticide resistance bioassays using the WHO's standard susceptibility tests from 2013 to 2018. During the same period, the frequency of the target-site knockdown resistance allele (kdr) in the local vector population was also determined via PCR for detection of the L1014 F mutation. Biochemical analysis for metabolic resistance was also conducted in 2015. From 2016-2017, Fludora™ fusion, a formulated combination of clothianidin (a neonicotinoid) and deltamethrin (a pyrethroid) was evaluated for 9 months on Bioko Island, using the WHO's standard test procedure for determining residual effectiveness of insecticides on sprayed surfaces. In 2016, the mortality rate of the vectors on 0.05% deltamethrin was as low as 38%. The frequency of the West African form of knockdown resistance allele, L1014 F, in the vector population was as high as 80%, and metabolic resistance analysis indicated high upregulated cytochrome P450 s. However, the residual effectiveness of Fludora™ fusion recorded mortalities above 80% after 72 h of exposure for 8 months. Although both target-site knockdown resistance and metabolic resistance to pyrethroids were implicated in the local malaria vector population, Fludora™ fusion was effective under field conditions in controlling the resistant vectors for a period of 8 months on wooden surfaces on Bioko Island and represents a valuable addition to IRS programs, especially in regions with high levels of pyrethroid resistance.


Assuntos
Anopheles/efeitos dos fármacos , Guanidinas/farmacologia , Controle de Mosquitos/métodos , Mosquitos Vetores/efeitos dos fármacos , Neonicotinoides/farmacologia , Nitrilos/farmacologia , Piretrinas/farmacologia , Tiazóis/farmacologia , Animais , Guiné Equatorial/epidemiologia , Guanidinas/administração & dosagem , Guanidinas/química , Humanos , Resistência a Inseticidas/genética , Inseticidas/administração & dosagem , Inseticidas/química , Inseticidas/farmacologia , Ilhas , Malária/epidemiologia , Malária/prevenção & controle , Neonicotinoides/administração & dosagem , Neonicotinoides/química , Nitrilos/administração & dosagem , Nitrilos/química , Piretrinas/administração & dosagem , Piretrinas/química , Tiazóis/administração & dosagem , Tiazóis/química
14.
Anticancer Res ; 39(5): 2429-2435, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31092435

RESUMO

BACKGROUND/AIM: Perfluorooctanoic acid (PFOA) is one of the most common perfluorinated compounds widely used in several applications. Due to its persistence in the environment, PFOA has been associated with various diseases, including cancer. This study explored the effects of PFOA on follicular thyroid carcinoma cells (FTC133). MATERIALS AND METHODS: Cell invasion, migration, adhesion and activity of matrix metalloproteinase-2 (MMP-2) were investigated using Transwell assays, adhesion assay and gelatin zymography, respectively. The underlying mechanism involved in the effects observed was evaluated by immunoblot analyses. RESULTS: Treatment with PFOA did not affect cell migration, but enhanced cell invasion, adhesion and activity of MMP-2 in FTC133 cells. PFOA selectively enhanced the phosphorylation of nuclear factor kappa B (NF-κB) p65, as well as induced NF-κB nuclear translocation. Treatment with a NF-κB inhibitor (BAY 11-7085) was able to reverse PFOA-induced cell invasiveness. CONCLUSION: PFOA promotes invasiveness of FTC133 cells mediated through the activation of NF-κB signaling.


Assuntos
Adenocarcinoma Folicular/tratamento farmacológico , Caprilatos/farmacologia , Fluorcarbonetos/farmacologia , Metaloproteinase 2 da Matriz/genética , Fator de Transcrição RelA/genética , Adenocarcinoma Folicular/genética , Adenocarcinoma Folicular/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , NF-kappa B/antagonistas & inibidores , NF-kappa B/genética , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Nitrilos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Sulfonas/farmacologia , Fator de Transcrição RelA/antagonistas & inibidores , Ativação Transcricional/efeitos dos fármacos
15.
Nat Commun ; 10(1): 1897, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015486

RESUMO

The cellular decision regarding whether to undergo proliferation or death is made at the restriction (R)-point, which is disrupted in nearly all tumors. The identity of the molecular mechanisms that govern the R-point decision is one of the fundamental issues in cell biology. We found that early after mitogenic stimulation, RUNX3 binds to its target loci, where it opens chromatin structure by sequential recruitment of Trithorax group proteins and cell-cycle regulators to drive cells to the R-point. Soon after, RUNX3 closes these loci by recruiting Polycomb repressor complexes, causing the cell to pass through the R-point toward S phase. If the RAS signal is constitutively activated, RUNX3 inhibits cell cycle progression by maintaining R-point-associated genes in an open structure. Our results identify RUNX3 as a pioneer factor for the R-point and reveal the molecular mechanisms by which appropriate chromatin modifiers are selectively recruited to target loci for appropriate R-point decisions.


Assuntos
Pontos de Checagem do Ciclo Celular/genética , Cromatina/química , Subunidade alfa 3 de Fator de Ligação ao Core/genética , Células Epiteliais/metabolismo , Regulação da Expressão Gênica , Animais , Butadienos/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cromatina/efeitos dos fármacos , Cromatina/metabolismo , Montagem e Desmontagem da Cromatina/efeitos dos fármacos , Subunidade alfa 3 de Fator de Ligação ao Core/antagonistas & inibidores , Subunidade alfa 3 de Fator de Ligação ao Core/metabolismo , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 4 Dependente de Ciclina/genética , Quinase 4 Dependente de Ciclina/metabolismo , Drosophila melanogaster/citologia , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Células HEK293 , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Humanos , Imidazóis/farmacologia , MAP Quinase Quinase 1/antagonistas & inibidores , MAP Quinase Quinase 1/genética , MAP Quinase Quinase 1/metabolismo , MAP Quinase Quinase 4/antagonistas & inibidores , MAP Quinase Quinase 4/genética , MAP Quinase Quinase 4/metabolismo , Proteína de Leucina Linfoide-Mieloide/genética , Proteína de Leucina Linfoide-Mieloide/metabolismo , Nitrilos/farmacologia , Piperazinas/farmacologia , Proteínas do Grupo Polycomb/genética , Proteínas do Grupo Polycomb/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Piridinas/farmacologia , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Proteínas ras/genética , Proteínas ras/metabolismo
16.
Malar J ; 18(1): 112, 2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30940139

RESUMO

BACKGROUND: Physiological characteristics (age and blood feeding status) of malaria vectors can influence their susceptibility to the current vector control tools that target their feeding and resting behaviour. To ensure the sustainability of the current and future vector control tools an understanding of how physiological characteristics may contribute to insecticide tolerance in the field is fundamental for shaping resistance management strategies and vector control tools. The aim of this study was to determine whether blood meal and mosquito age affect pyrethroid tolerance in field-collected Anopheles gambiae from western Kenya. METHODS: Wild mosquito larvae were reared to adulthood alongside the pyrethroid-susceptible Kisumu strain. Adult females from the two populations were monitored for deltamethrin resistance when they were young at 2-5 days old and older 14-16 days old and whether fed or unfed for each age group. Metabolic assays were also performed to determine the level of detoxification enzymes. Mosquito specimens were further identified to species level using the polymerase chain reaction (PCR) method. RESULTS: Anopheles gambiae sensu stricto was the predominant species comprising 96% of specimens and 2.75% Anopheles arabiensis. Bioassay results showed reduced pyrethroid induced mortality with younger mosquitoes compared to older ones (mortality rates 83% vs. 98%), independently of their feeding status. Reduced mortality was recorded with younger females of which were fed compared to their unfed counterparts of the same age with a mortality rate of 35.5% vs. 83%. Older blood-fed females showed reduced susceptibility after exposure when compared to unfed females of the same age (mortality rates 86% vs. 98%). For the Kisumu susceptible population, mortality was straight 100% regardless of age and blood feeding status. Blood feeding status and mosquito age had an effect on enzyme levels in both populations, with blood fed individuals showing higher enzyme elevations compared to their unfed counterparts (P < 0.0001). The interaction between mosquito age and blood fed status had significant effect on mosquito mortality. CONCLUSION: The results showed that mosquito age and blood feeding status confers increased tolerance to insecticides as blood feeding may be playing an important role in the toxicity of deltamethrin, allowing mosquitoes to rest on insecticide-treated materials despite treatment. These may have implications for the sustained efficacy of indoor residual spraying and insecticide-treated nets based control programmes that target indoor resting female mosquitoes of various gonotrophic status.


Assuntos
Anopheles/efeitos dos fármacos , Anopheles/fisiologia , Tolerância a Medicamentos , Inseticidas/farmacologia , Piretrinas/farmacologia , Fatores Etários , Animais , Anopheles/classificação , Anopheles/genética , Comportamento Alimentar , Feminino , Técnicas de Genotipagem , Quênia , Nitrilos/farmacologia , Reação em Cadeia da Polimerase
17.
Parasit Vectors ; 12(1): 167, 2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30975185

RESUMO

BACKGROUND: Culex pipiens pallens is the most abundant Culex mosquito species in northern China and is an important vector of bancroftian filariasis and, potentially, West Nile virus. Insecticides, particularly pyrethroids, are widely used for adult mosquito control. Insecticide resistance has become common in several mosquito species, and vector control is the main method currently available to prevent disease transmission. The voltage-gated sodium channel (Vgsc) gene is the target site of pyrethroids, and mutations in this gene cause knockdown resistance (kdr). METHODS: Culex pipiens pallens larvae were collected from May to November over two decades, from 1992 to 2018, in four cities in Shandong Province, China. The World Health Organization (WHO) standard resistance bioassay was applied to test the resistance levels of Cx. p. pallens larvae to five different insecticides and to test deltamethrin resistance in adults, using the F1 generation. Mutations at Vgsc codon 1014 were also screened in 471 adult samples collected in 2014 to determine the association between kdr mutations and phenotypic resistance. RESULTS: Larval resistance against deltamethrin showed an increasing trend from the 1990s until 2018, which was statistically significant in all populations; resistance to cypermethrin increased significantly in mosquitoes from the Zaozhuang population. However, larval resistance to other insecticides remained relatively stable. Larval resistance against deltamethrin was consistent with adult bioassays in 2014, in which all tested populations were highly resistant, with mortality rates ranging from 39.4 to 55.23%. The L1014S and L1014F mutations were both observed in five Cx. p. pallens populations, with L1014F significantly associated with deltamethrin resistance. CONCLUSIONS: The long-term dataset from Shandong demonstrates major increases in pyrethroid resistance over a 20-year period. The L1014F kdr mutation may be considered a viable molecular marker for monitoring pyrethroid resistance in Cx. p. pallens.


Assuntos
Culex/efeitos dos fármacos , Resistência a Inseticidas , Animais , China , Culex/genética , Feminino , Resistência a Inseticidas/genética , Inseticidas/farmacologia , Mutação , Nitrilos/farmacologia , Piretrinas/farmacologia , Canais de Sódio Disparados por Voltagem/genética
18.
Exp Parasitol ; 201: 34-41, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31034815

RESUMO

Ovine Eimeria spp. infections cause increased mortality, reduced welfare and substantial economic losses, and anticocccidials are important for their control. Recent reports of anticoccidial resistance against ovine Eimeria spp. necessitate the development of in vitro methods for the detection of reduced anticoccidial efficacy, especially since the in vivo methods are both expensive, time consuming and requires the use of otherwise healthy animals. The aim of the present study was therefore to approach a preliminary standardization of in vitro assays for evaluation of the efficacy of the most commonly used anticoccidials in ruminants. For this purpose, apart from the evaluation of inhibition of oocyst sporulation, most effort was concentrated on assessment of the capacity of the different anticoccidials to inhibit both the invasion and further development (up to the first schizogony) of E. ninakohlyakimovae sporozoites in bovine colonic epithelial cells (BCEC). For this purpose, infected cultures were monitored 1, 8 and 15 days post infection to determine the infection rate, number of immature schizonts and number, size and appearance of mature schizonts, respectively. No clear inhibitory effect was found with any of the anticoccidial formulations tested, and we could not identify why there were no measurable effects from the different anticoccidials. Despite the lack of positive results, further investigations should be encouraged, as this could decrease the need for animal experiments and could be used in the initial assessment of anticoccidial efficacy of new drugs.


Assuntos
Coccidiose/veterinária , Coccidiostáticos/farmacologia , Eimeria/efeitos dos fármacos , Doenças das Cabras/parasitologia , Animais , Bovinos , Células Cultivadas , Coccidiose/tratamento farmacológico , Coccidiose/parasitologia , Colo/citologia , Colo/parasitologia , Decoquinato/farmacologia , Resistência a Medicamentos , Eimeria/crescimento & desenvolvimento , Eimeria/isolamento & purificação , Células Epiteliais/parasitologia , Fezes/parasitologia , Doenças das Cabras/tratamento farmacológico , Cabras , Mucosa Intestinal/citologia , Mucosa Intestinal/parasitologia , Nitrilos/farmacologia , Oocistos/isolamento & purificação , Esquizontes/efeitos dos fármacos , Esquizontes/crescimento & desenvolvimento , Esporozoítos/isolamento & purificação , Sulfonamidas/farmacologia , Triazinas/farmacologia
19.
Pestic Biochem Physiol ; 156: 129-137, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31027572

RESUMO

Chiral pesticides have been used in agriculture, including (±)-lambda-cyhalothrin ((±)-LC), which is a pyrethroid insecticide widely employed on crops for protection against different types of insects. However, enantioselectivity is poorly studied in biodegradation processes. Therefore, the (±)-LC enantioselective biodegradation by bacteria from Brazilian savannah was reported in this study with a validated analytical method. All bacterial strains biodegraded (±)-LC with different efficiencies. Residual concentrations of LC (3.7-43.1% of biodegradation) and its enantiomeric excesses (0-27% ee) were determined. Additionally, the formation of the main biodegradation metabolite 3-phenoxybenzoic acid was also quantified. A Bacillus consortium composed of the three most efficient strains biodegraded more LC than any isolated strain solely employed in this work, showing that the use of a consortium is an interesting approach. In addition, 13 metabolites were identified and a biodegradation pathway with biochemical reactions of hydrolysis, reduction, esterification, amidation, elimination and group transfer were proposed, confirming the bioremediation potential of these strains. The LC stereoisomer with the highest insecticidal activity (1R,3R,αS-enantiomer, also known as gamma-cyhalothrin) was preferentially biodegraded by the studied bacteria. Therefore, crops protection with gamma-cyhalothrin, which can be applied in lower concentrations than (±)-LC because it is a more effective product against insects, may also be biodegraded faster than the racemic mixture in the environment, decreasing the toxic effects on non-target organisms.


Assuntos
Bactérias/metabolismo , Nitrilos/farmacologia , Piretrinas/farmacologia , Bacillus/metabolismo , Biodegradação Ambiental , Inseticidas/farmacologia , Praguicidas/farmacologia , Estereoisomerismo
20.
Pestic Biochem Physiol ; 156: 87-95, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31027585

RESUMO

Environmental pollutants, such as insecticides, can alter the equilibrium of aquatic ecosystems, particularly those closely located to human occupations. The use of such anthropogenic compounds frequently results in the selection of resistant individuals. However, how the underlying insecticide resistance mechanisms interplay with the abilities of the resistant individuals to cope with other environmental challenges (e.g., predators) has not received adequate attention. Here, we evaluated whether resistance to pyrethroid insecticides in larvae of the yellow fever mosquito, Aedes aegypti (Diptera: Culicidae), would affect their abilities to survive other environmental challenges. We assessed the susceptibilities of the pyrethroid-resistant larvae to other insecticides (i.e., the oxadiazine indoxacarb and juvenile hormone mimic pyriproxyfen) and determined the activities of potential detoxification enzymes. Finally, we also recorded potential alterations in larva swimming behavior in the presence of predators, such as the water bug Belostoma anurum (Hemiptera: Belostomatidae). Our results revealed that high pyrethroid resistance was associated with moderate resistance to the other two insecticides. Furthermore, this multiple resistance was associated with higher detoxification activity by glutathione-S-transferases and general esterases. Interestingly, in comparison with insecticide-susceptible larvae, the pyrethroid-resistant larvae not only swam for longer periods and distances, but also took longer to be captured by B. anurum nymphs. Collectively, our findings revealed increased abilities to survive natural environmental challenges (e.g., predatory attacks) in mosquito larvae that express physiological and behavioral changes associated with multiple resistance to insecticides.


Assuntos
Aedes/efeitos dos fármacos , Inseticidas/farmacologia , Larva/efeitos dos fármacos , Animais , Bioensaio , Resistência a Inseticidas , Nitrilos/farmacologia , Piretrinas/farmacologia
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