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BACKGROUND: Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV. METHODS: Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses. RESULTS: ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for CL/F was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure( P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively). CONCLUSIONS: Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure. TRIAL REGISTRATION: Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).
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INTRODUCTION: Madecassic acid (MA), a triterpene compound isolated from Centella Asiatica herbs, has previously been shown to attenuate colitis induced by DSS in mice. In the present study, we address whether and how MA ameliorates colitis-associated colorectal cancer (CAC), which accounts for a considerable proportion of colorectal cancer. METHODS: CAC was induced by AOM/DSS in mice, and MA was administered orally once a day. To identify the source cells of IL-17 and the target cells for MA reducing the expression of IL-17 in the colons of CAC mice, single-cell suspensions were prepared from the colons of CAC mice and analyzed by flow cytometry. An adoptive transfer experiment was performed to verify the importance of the decreasing γδT17 cell population in the anti-CAC effect of MA. RESULTS: Oral administration of MA reduced the burden and incidence of tumors in the CAC mice. MA decreased the number of MDSCs in the colon tissues of CAC mice and ameliorated anti-tumor immune responses. MA could prevent the migration of MDSCs by inhibiting the activation of γδT17 cells and the expression of chemokines. The population of activated-γδT17 cells in the tumor microenvironment of CAC mice positively correlated with the number of MDSCs and tumors as well as tumor load. Moreover, the anti-CAC effect of MA was significantly counteracted by the adoptive transfer of γδT17 cells. CONCLUSIONS: MA alleviates CAC by blocking the recruitment of MDSCs to increase the population of anti-tumor immune cells in tumor microenvironment via inhibition of the activation of γδT17 cells.
Assuntos
Neoplasias Associadas a Colite , Colite , Neoplasias Colorretais , Células Supressoras Mieloides , Triterpenos , Animais , Azoximetano , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Neoplasias Colorretais/metabolismo , Sulfato de Dextrana , Modelos Animais de Doenças , Interleucina-17/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Transdução de Sinais , Células Th17 , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Microambiente TumoralRESUMO
Intestinal mucus barrier dysfunction is closely involved in the pathogenesis of inflammatory bowel diseases (IBD). To investigate the protective effect and underlying mechanism of arctigenin, a phytoestrogen isolated from the fruits of Arctium lappa L., on the intestinal mucus barrier under colitis condition. The role of arctigenin on the intestinal mucus barrier and the apoptosis of goblet cells were examined by using both in vitro and in vivo assays. Arctigenin was demonstrated to promote the mucus secretion and maintain the integrity of mucus barrier, which might be achieved by an increase in the number of goblet cells via inhibiting apoptosis. Arctigenin selectively inhibited the mitochondrial pathway-mediated apoptosis. Moreover, arctigenin elevated the protein level of prohibitin 1 (PHB1) through blocking the ubiquitination via activation of estrogen receptor ß (ERß) to competitively interact with PHB1 and disrupt the binding of tripartite motif 21 (TRIM21) with PHB1. ERß knock down in the colons of mice with DSS-induced colitis resulted in significant reduction of the protection of arctigenin and DPN against the mucosal barrier. Arctigenin can maintain the integrity of the mucus barrier by inhibiting the apoptosis of goblet cells through the ERß/TRIM21/PHB1 pathway.
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Colite , Doenças Inflamatórias Intestinais , Animais , Apoptose , Colite/induzido quimicamente , Receptor beta de Estrogênio/metabolismo , Furanos , Células Caliciformes/metabolismo , Células Caliciformes/patologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/patologia , Lignanas , Camundongos , Camundongos Endogâmicos C57BL , Muco/metabolismo , Fitoestrógenos , ProibitinasRESUMO
The elevated intestinal permeability due to mucosal barrier defects is not only secondary to inflammatory bowel disease but also precedes enteritis. Tetrandrine, a bisbenzyl isoquinoline alkaloid isolated from the dried roots of Stephamis tetlandra S. Moor, was previously demonstrated to ameliorate colitis induced by dextran sulfate sodium (DSS) in mice. Here, we investigate whether and how tetrandrine protects against the disruption of the intestinal epithelial barrier under colitis condition. The data show that oral administration of tetrandrine significantly counteracted the increase of intestinal permeability in DSS-treated mice, enhanced the mRNA and protein expression of Occludin and Claudin1 in the colon, but hardly affected the expression of ZO-1 and Mucin2. In vitro, tetrandrine treatment rescued the decrease of monolayer transmembrane resistance and the increase of epithelial cell permeability induced by TNF-α, upregulated the expression of Occludin, and downregulated the expression of Claudin1 but did not affect the expression of ZO-1. The siRNA of Occludin largely weakened the protective effect of tetrandrine on the epithelial barrier function in Caco-2 cells. MiR-429 mimic obviously counteracted the upregulation of tetrandrine on the expression of Occludin and the amelioration on epithelial barrier defects, in contrast, miR-429 inhibitor showed the opposite effects. The antagonist (CH223191) and siAhR of aryl hydrocarbon receptor (AhR) nearly completely diminished the effects of tetrandrine, including inhibition of the miR429 expression, the upregulation of Occludin expression, and amelioration of intestinal epithelial barrier defects in Caco-2 cells. In colitis mice, CH223191 significantly weakened the protective effect of tetrandrine on colitis and intestinal mucosal barrier and diminished the downregulation on miR-429 expression and the promotion on Occludin expression in the colon. In summary, tetrandrine can attenuate the intestinal epithelial barrier defects in colitis through promoting Occludin expression via the AhR/miR-429 pathway, and it might be used to treat colitis as a barrier protector.
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Benzilisoquinolinas/farmacologia , Colite/complicações , Enteropatias/tratamento farmacológico , Mucosa Intestinal/efeitos dos fármacos , MicroRNAs/genética , Ocludina/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Colite/induzido quimicamente , Colite/patologia , Sulfato de Dextrana/toxicidade , Feminino , Regulação da Expressão Gênica , Humanos , Enteropatias/etiologia , Enteropatias/metabolismo , Enteropatias/patologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Camundongos , Camundongos Endogâmicos C57BL , Ocludina/genética , Permeabilidade , Receptores de Hidrocarboneto Arílico/genéticaRESUMO
Type-17 immune response, mediated mainly by IL-17, plays a critical role in ulcerative colitis. Previously, we showed that madecassic acid (MA), the main active ingredient of Centella asiatica herbs for anti-colitis effect, ameliorated dextran sulfate sodium (DSS)-induced mouse colitis through reducing the level of IL-17. Here, we explore the effect of MA on the activation of γδT17 cells, an alternative source of IL-17 in colitis. In DSS-induced colitis mice, oral administration of MA decreased the number of γδT17 cells and attenuated the inflammation in the colon, and the anti-colitis effect of MA was significantly counteracted by redundant γδT17 cells, suggesting that the decrease in γδT17 cells is important for the anti-colitis effect of MA. In vitro, MA could inhibit the activation but not the proliferation of γδT17 cells at concentrations without evident cytotoxicity. Antibody microarray profiling showed that the inhibition of MA on the activation of γδT17 cells involved PPARγ-PTEN/Akt/GSK3ß/NFAT signals. In γδT17 cells, MA could reduce the nuclear localization of NFATc1 through inhibiting Akt phosphorylation to promote GSK3ß activation. Moreover, it was confirmed that MA inhibited the Akt/GSK3ß/NFATc1 pathway and the activation of γδT17 cells through activating PPARγ to increase PTEN expression and phosphorylation. The correlation between activation of PPARγ, decrease in γδT17 cell number, and amelioration of colitis by MA was validated in mice with DSS-induced colitis. In summary, these findings reveal that MA inhibits the activation of γδT17 cells through PPARγ-PTEN/Akt/GSK3ß/NFAT pathway, which contributes to the amelioration of colitis.
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Colite Ulcerativa/tratamento farmacológico , Interleucina-17/metabolismo , PPAR gama/metabolismo , Triterpenos/uso terapêutico , Animais , Feminino , Humanos , Camundongos , Triterpenos/farmacologiaRESUMO
Arctigenin, the major active constituent of Fructus Arctii, has been reported to inhibit the growth of various tumors and alleviate colitis. This study aimed to prove the protective effect of arctigenin on colitis-associated cancer (CAC) and explore its mechanisms. Orally administered arctigenin prevented the progression of colitis and protected against colon carcinogenesis in azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CAC mice. Arctigenin downregulated NLRP3 inflammasome activation and fatty acid oxidation (FAO) metabolism in macrophages, as determined by untargeted metabolomics. Arctigenin also inhibited the expression of carnitine palmitoyltransferase 1 (CPT1), reduced the acetylation of α-tubulin, and disrupted NLRP3 complex formation, which in turn inactivated the NLRP3 inflammasome. Downregulation of the CPT1-FAO-acetyl-coenzyme A (acetyl-CoA)-acetylated α-tubulin pathway was observed to inhibit the effect of arctigenin on NLRP3 inflammasome assembly, as confirmed by CPT1 overexpression. Lastly, arctigenin was shown to inhibit NLRP3 inflammasome activation and improve CAC in mice, and the effect was significantly diminished by the overexpression of adeno-associated virus (AAV)9-CPT1. Taken together, these results show that the inhibition of NLRP3 inflammasome assembly in macrophages due to FAO downregulation contributes to the preventative effect of arctigenin against CAC. Our findings highlight the potential value of arctigenin to reduce the risk of CAC in patients with colitis.
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Neoplasias Associadas a Colite/prevenção & controle , Colo/efeitos dos fármacos , Ácidos Graxos/metabolismo , Furanos/farmacologia , Inflamassomos/antagonistas & inibidores , Lignanas/farmacologia , Macrófagos/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Animais , Carnitina O-Palmitoiltransferase/antagonistas & inibidores , Colo/metabolismo , Regulação para Baixo , Inflamassomos/fisiologia , Interleucina-1beta/antagonistas & inibidores , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/fisiologia , OxirreduçãoRESUMO
Intestinal epithelial barrier dysfunction is deeply involved in the pathogenesis of inflammatory bowel diseases (IBD). Arctigenin, the main active constituent in Fructus Arctii (a traditional Chinese medicine), has previously been found to attenuate colitis induced by dextran sulfate sodium (DSS) in mice. The present study investigated whether and how arctigenin protects against the disruption of the intestinal epithelial barrier in IBD. Arctigenin maintained the intestinal epithelial barrier function of mice with DSS- and TNBS-induced colitis. In Caco-2 and HT-29 cells, arctigenin lowered the monolayer permeability, increased TEER, reversed the abnormal expression of tight junction proteins, and restored the altered localization of F-actin induced by TNF-α and IL-1ß. The specific antagonist PHTPP or shRNA of ERß largely weakened the protective effect of arctigenin on the epithelial barrier function of Caco-2 and HT-29 cells. Molecular docking demonstrated that arctigenin had high affinity for ERß mainly through hydrogen bonds as well as hydrophobic effects, and the protective effect of arctigenin on the intestinal barrier function was largely diminished in ERß-mutated (ARG346 and/or GLU305) Caco-2 cells. Moreover, arctigenin-blocked TNF-α induced increase of the monolayer permeability in Caco-2 and HT-29 cells and the activation of myosin light chain kinase (MLCK)/myosin light chain (MLC) pathway in an ERß-dependent manner. ERß deletion in colons of mice with DSS-induced colitis resulted in a significant attenuation of the protective effect of arctigenin on the barrier integrity and colon inflammation. Arctigenin maintained the integrity of the intestinal epithelial barrier under IBD by upregulating the expression of tight junction proteins through the ERß-MLCK/MLC pathway.
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Receptor beta de Estrogênio/agonistas , Furanos/farmacologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/metabolismo , Mucosa Intestinal/metabolismo , Lignanas/farmacologia , Animais , Células CACO-2 , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Feminino , Células HT29 , Humanos , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/patologia , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Mucosa Intestinal/patologia , Camundongos , Camundongos Endogâmicos BALB C , Mutação de Sentido Incorreto , Quinase de Cadeia Leve de Miosina/genética , Quinase de Cadeia Leve de Miosina/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
AIMS: Sinomenine, an anti-rheumatoid arthritis drug used in China for decades, is usually co-administered with cardiovascular (CV) drugs to reduce arthritis-related risk of cardiovascular diseases. This study was to investigate whether and how CV drugs affect the pharmacokinetic profile of sinomenine. MAIN METHODS: In rat liver microsomes (RLMs), the key metabolic enzymes of sinomenine were identified by using specific inhibitors. The influences of CV drugs, including propranolol, verapamil, warfarin, atorvastatin, simvastatin, and lovastatin, on the metabolism of sinomenine were examined. Cocktail probe, RT-qPCR, and western blotting were performed to unveil the underlying mechanism of the drug-drug interaction. KEY FINDINGS: The key metabolic enzymes of sinomenine were identified to be CYP3A1/2 and CYP2D1 in RLMs. Among the CV drugs screened, simvastatin and lovastatin were shown to inhibit the liver metabolism of sinomenine with Ki values of 13.00 and 25.83⯵M, respectively. Single administration of simvastatin or lovastatin in rats increased the AUC value of sinomenine to 1.40- or 1.50-fold, and decreased the CLz/F value to 68.19% or 65.44%, respectively. In contrast, multiple administrations of simvastatin, but not lovastatin, increased the CLz/F value of sinomenine to 1.38-fold and decreased the AUC value to 71.59%. Further studies showed that the long-term administration of simvastatin could up-regulate the expression of CYP3A1/2 to account for the effect. SIGNIFICANCE: This study demonstrated the potential effect of simvastatin and lovastatin on the metabolism of sinomenine for the first time. The findings provide guidelines for the co-administration of sinomenine with simvastatin or lovastatin in clinic.
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Sistema Enzimático do Citocromo P-450/metabolismo , Lovastatina/administração & dosagem , Microssomos Hepáticos/metabolismo , Morfinanos/farmacocinética , Sinvastatina/administração & dosagem , Animais , Antirreumáticos/farmacocinética , Combinação de Medicamentos , Interações Medicamentosas , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Masculino , Microssomos Hepáticos/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Distribuição TecidualRESUMO
Tetrandrine is an effective ingredient isolated from the roots of a frequently used medicinal plant Stephania tetrandra S. Moore. It has been used for the management of arthritis in China, but the precise mechanism remains unclear. In the present study, a metabolomics method based on the 1H NMR was constituted to quantify the alterations of the endogenous metabolites in the urines of collagen-induced arthritis (CIA) rats treated with tetrandrine. Data showed that tetrandrine treatment could alleviate the ankle joint swelling and ameliorate histopathological changes in rats. The metabonomic analysis indicated that 23 potential biomarkers in urine were affiliated with CIA. They mainly participated in energy metabolism, amino acid metabolism, lipid metabolism and gut microbe metabolism. Moreover, our results implied that tetrandrine could reverse the pathological process of CIA through adjusting the unbalanced metabolic pathways. Thus, these metabolic pathways and potential biomarkers might be the potential therapeutic targets of tetrandrine, and these findings supplied new visions into the protective effect of tetrandrine against arthritis in rats.
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Artrite Experimental/tratamento farmacológico , Artrite Experimental/urina , Benzilisoquinolinas/farmacologia , Biomarcadores/urina , Colágeno/farmacologia , Urina/química , Aminoácidos/metabolismo , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/metabolismo , Biomarcadores/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Metabolismo Energético/efeitos dos fármacos , Feminino , Metabolismo dos Lipídeos/efeitos dos fármacos , Redes e Vias Metabólicas/efeitos dos fármacos , Metabolômica/métodos , Plantas Medicinais/química , Espectroscopia de Prótons por Ressonância Magnética/métodos , RatosRESUMO
Emamectin benzoate (EMB), a novel macrocyclic lactone insecticide, possesses high efficacy and beneficial selective toxicity in agriculture, but so far the EMB-induced cytotoxic action in arthropod insect remains unclear. The present studies were carried out to characterize the property of EMB on the induction of reactive oxygen species (ROS)-mediated DNA damage and apoptosis in Trichoplusia Tn5B1-4 cell model. Following the exposure to EMB at 2.5, 5, 10 or 15 µM, the cells changed to be round, suspended and aggregated, and the decline of cell proliferating ability and cell viability was positively related with the exposure time. Median inhibitory concentration (IC50) of EMB on cell viability was 3.72 µM during 72 h exposure. Apoptosis was induced in 29.8% (24 h) and 39.5% (48 h) of the cells by EMB at 15 µM, showing chromatin condensation in nuclei. The content of ROS in the cells increased rapidly as the concentration of EMB increased, and the pre-incubation of the cells with vitamin E significantly reduced the ROS accumulation. In the treatment of 15 µM EMB, the migrated cell nucleus with DNA strand breaks appeared a teardrop, pear-shaped, or large fan-like tail, and 63.1% of γH2AX-positive cells contained more than four foci, accompanying with high expression level of caspase-3 in time-dependent manner, which consequently led to cell apoptotic death. These evidences in ROS-mediated DNA damage and cell apoptosis induced by EMB may be helpful for deep understanding the cytotoxic action of EMB based on cell model.
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Apoptose/efeitos dos fármacos , Dano ao DNA , Ivermectina/análogos & derivados , Espécies Reativas de Oxigênio/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Ivermectina/farmacologia , Lepidópteros , Relação Estrutura-AtividadeRESUMO
Leukemia threatens millions of people's health and lives, and the pesticide-induced leukemia has been increasingly concerned because of the etiologic exposure. In this paper, cytotoxic effect of emamectin benzoate (EMB), an excellent natural-product insecticide, was evaluated through monitoring cell viability, cell apoptosis, mitochondrial membrane potential and intracellular Ca2+ concentration ([Ca2+]i) in leukemia K562 and Molt-4 cells. Following the exposure to EMB, cell viability was decreased and positive apoptosis of K562 and Molt-4 cells was increased in a concentration- and time- dependent fashion. In the treatment of 10µM EMB, apoptotic cells accounted for 93.0% to K562 cells and 98.9% to Molt-4 cells based on the control, meanwhile, 63.47% of K562 cells and 81.15% of Molt-4 cells exhibited late apoptotic and necrotic features with damaged cytoplasmic membrane. 48h exposure to 10µM EMB increased significantly the great number of cells with mitochondrial membrane potential (MMP) loss, and the elevation of [Ca2+]i level was peaked and persisted within 70s in K562 cells whilst 50s in Molt-4 cells. Moreover, a stronger cytotoxicity of EMB was further observed than that of imatinib. The results authenticate the efficacious effect of EMB as a potential anti-leukemia agent and an inconsistency with regard to insecticide-induced leukemia.
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Inseticidas/toxicidade , Ivermectina/análogos & derivados , Apoptose/efeitos dos fármacos , Cálcio/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Ivermectina/toxicidade , Células K562 , Leucemia , Potencial da Membrana Mitocondrial/efeitos dos fármacosRESUMO
Photodynamic sensitizers as useful alternative agents have been used for population control against insect pests, and the response of insect ovarian cells towards the photosensitizers is gaining attention because of the next reproduction. In this paper, antioxidative responses of lepidopteran ovarian Tn5B1-4 and Sf-21 cells to photoactivated alpha-terthienyl (PAT) are investigated. PAT shows positive inhibitory cytotoxicity on the two ovarian cells, and its inhibition on cell viability is enhanced as the concentrations are increased and the irradiation time is extended. Median inhibitory concentrations (IC50) are 3.36µg/ml to Tn5B1-4 cells, and 3.15µg/ml to Sf-21 cells at 15min-UV-A irradiation 2h-dark incubation. Under 10.0µg/ml PAT exposure, 15min-UV-A irradiation excites higher ROS production than 5min-UV-A irradiation does in the ovarian cells, the maximum ROS content is about 7.1 times in Tn5B1-4 cells and 4.3 times in Sf-21 cells, and the maximum malondialdehyde levels in Tn5B1-4 and Sf-21 cells are about 1.47- and 1.36-fold higher than the control groups, respectively. Oxidative stress generated by PAT strongly decreases the activities of POD, SOD and CAT, and induces an accumulation of Tn5B1-4 cells in S phase and Sf-21 cells in G2/M phase in a concentration-dependent fashion. Apoptosis accumulation of Tn5B1-4 cells and the persistent post-irradiation cytotoxicity are further observed, indicating different antioxidative tolerance and arrest pattern of the two ovarian cells towards the cytotoxicity of PAT.
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Antioxidantes/metabolismo , Inseticidas/farmacologia , Lepidópteros/efeitos dos fármacos , Ovário/efeitos dos fármacos , Tiofenos/farmacologia , Raios Ultravioleta , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Técnicas de Cultura de Células , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/efeitos da radiação , Linhagem Celular , Feminino , Citometria de Fluxo , Inseticidas/efeitos da radiação , Lepidópteros/citologia , Ovário/citologia , Ovário/metabolismo , Ovário/efeitos da radiação , Tiofenos/efeitos da radiaçãoRESUMO
The cytotoxic potential of 13 commonly used agricultural insecticides was examined using cell-based systems with three human HepG2, Hek293, HeLa cells and three insect Tn5B1-4, Sf-21, and Drosophila S2 cells. Data showed that (1) an enhancement of some insecticides (e.g. pyrethroids) on cells proliferation; (2) an inhibition of some insecticides on cells viability; (3) various levels of susceptibility of different cells to the same insecticide; and (4) the cell type dependent sensitivity to different insecticides. The degree of cytotoxicity of insecticides on human cells was significantly lower than that on insect cells (P<0.05). Methomyl, even 20µg/ml, showed little cytotoxicity at 24h exposure whereas emamectin benzoate possessed the strongest cytotoxic potential in a dose-dependent fashion. The results revealed comparable cytotoxic property of agricultural insecticides against intact cells.