RESUMEN
Fungicides are pesticides that are frequently used in agriculture because of their action against fungal diseases. However, the widespread application of pesticides around the world raises environmental and public health concerns, since these compounds are toxic and can pose risks to ecosystems and human health. The aim of this study was to evaluate the phytotoxic, cytogenotoxic, and biochemical effects of azoxystrobin and carbendazim on Lactuca sativa L. and their physiological effects on Phaseolus vulgaris L. by analyzing the cell cycle and chromosomal and nuclear alterations in L. sativa; the biochemical effects of azoxystrobin and carbendazim on Phaseolus vulgaris L. and their physiological effects on Phaseolus vulgaris L. by analyzing the cell cycle and chromosomal and nuclear alterations in L. sativa; the biochemical effects by analyzing the activity of antioxidant enzymes in L. sativa; and the physiological effects by analyzing chlorophyll content and chlorophyll a fluorescence in P. vulgaris. It was observed that both fungicides were phytotoxic and cytotoxic, reducing root growth and the mitotic index, cytogenotoxic, increasing the occurrence of chromosomal alterations, as well as inducing oxidative stress and an increase in chlorophyll fluorescence emission and altered energy absorption in the plants used as a test system. In view of this, studies such as the one presented here indicate that the use of pesticides, even in small quantities, can lead to damage to the metabolism of plant organisms.
Asunto(s)
Bencimidazoles , Carbamatos , Fungicidas Industriales , Lactuca , Phaseolus , Estrobilurinas , Phaseolus/efectos de los fármacos , Estrobilurinas/toxicidad , Bencimidazoles/toxicidad , Fungicidas Industriales/toxicidad , Carbamatos/toxicidad , Lactuca/efectos de los fármacos , Pirimidinas/toxicidad , Clorofila/metabolismoRESUMEN
The use of agrochemicals in agriculture may impact aquatic ecosystems, particularly influencing the stream insect communities. Among aquatic insects, the family Chironomidae is the most abundant and species-diverse insect group found in freshwater ecosystems. However, in the southern hemisphere, studies with Chironomidae are still sparse, compared to Europe and North America. The present study evaluates the responses of Chironomidae species (Insecta: Diptera) to pyrimethanil fungicide in a mesocosm experiment. Water contamination and chironomid community were monitored over 10 months. After five months of monitoring, the pyrimethanil fungicide was completely degraded and there was a statistically significant increase in the Margalef Richness and Shannon-Wiener Index (H') in the control units when compared with the contaminated mesocosms (p = 0.003). Our results point out that the utilization of agrochemicals can be a harmful factor influencing negatively the Chironomidae populations. This finding has key implications for insect conservation strategies and ecological management environments.
Asunto(s)
Chironomidae , Fungicidas Industriales , Animales , Ecosistema , Fungicidas Industriales/toxicidad , Pirimidinas/toxicidadRESUMEN
P-gp-associated multidrug resistance is a major impediment to the success of chemotherapy. With the aim of finding non-toxic and effective P-gp inhibitors, we investigated a panel of quinolin-2-one-pyrimidine hybrids. Among the active compounds, two of them significantly increased intracellular doxorubicin and rhodamine 123 accumulation by inhibiting the efflux mediated by P-gp and restored doxorubicin toxicity at nanomolar range. Structure-activity relationships showed that the number of methoxy groups, an optimal length of the molecule in its extended conformation, and at least one flexible methylene group bridging the quinolinone to the moiety bearing the pyrimidine favored the inhibitory potency of P-gp. The best compounds showed a similar binding pattern and interactions to those of doxorubicin and tariquidar, as revealed by MD and hybrid QM/MM simulations performed with the recent experimental structure of P-gp co-crystallized with paclitaxel. Analysis of the molecular interactions stabilizing the different molecular complexes determined by MD and QTAIM showed that binding to key residues from TMH 4-7 and 12 is required for inhibition.
Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Pirimidinas/farmacología , Quinolonas/farmacología , Muerte Celular/efectos de los fármacos , Humanos , Células K562 , Simulación de Dinámica Molecular , Transporte de Proteínas/efectos de los fármacos , Pirimidinas/química , Pirimidinas/toxicidad , Quinolonas/química , Quinolonas/toxicidad , Rodamina 123/metabolismo , Relación Estructura-Actividad , TermodinámicaRESUMEN
The ability to recover to original states after disturbances makes macroinvertebrates useful tools for assessing the impacts of pesticides. Many studies showed that direct exposure to pesticides decreases macroinvertebrate richness and alters their composition. The main objective of this study was to assess recovery patterns in macroinvertebrate communities after pesticide application in irrigated rice fields. We analyzed short-term temporal dynamics of macroinvertebrate communities after application of the herbicides bispyribac-sodium and clomazone and the insecticide chlorantraniliprole, over the rice-growing season in southern Brazil. We selected three conventional rice fields and the recovery of macroinvertebrate communities was also compared with three adjacent natural ponds. The study was developed from November 2011 to February 2012 (rice-growing season). Five macroinvertebrate collections were carried out 3, 7, 14, 38, and 60 days after pesticide application (November 25). Rice fields showed lower richness and abundance than ponds in the period immediately after pesticide application, and recovery rates in the richness of macroinvertebrate communities were more conspicuous as pesticide residuals dissipated from the fields. Macroinvertebrate community structure in rice fields also became more similar to natural ponds as pesticide traces were scarcer. However, macroinvertebrate abundance patterns were not related to pesticide concentrations in the fields. Our results supported the general hypothesis on the negative effects of pesticide application on macroinvertebrate community in irrigated rice fields, although other environmental features (e.g., length of the flooded period) also contributed to explain temporal dynamics in the macroinvertebrate communities from irrigated rice fields.
Asunto(s)
Riego Agrícola , Herbicidas/toxicidad , Insecticidas/toxicidad , Invertebrados/efectos de los fármacos , Oryza , Animales , Benzoatos/análisis , Benzoatos/toxicidad , Monitoreo del Ambiente/métodos , Herbicidas/análisis , Insecticidas/análisis , Isoxazoles/análisis , Isoxazoles/toxicidad , Oxazolidinonas/análisis , Oxazolidinonas/toxicidad , Pirimidinas/análisis , Pirimidinas/toxicidad , ortoaminobenzoatos/análisis , ortoaminobenzoatos/toxicidadRESUMEN
Acute lethal and sublethal toxicity of the pirimicarb-based commercial formulation Aficida® were evaluated on Boana pulchella tadpoles. Whereas mortality was used as end point for lethality, frequency of micronuclei and other nuclear abnormalities as well as alterations in the frequency of erythroblasts in circulating blood as biomarkers for genotoxicity and cytotoxicity, respectively. Swimming, growth, developmental and morphological abnormalities were also employed as sublethal end points. Results show that the species is within the 13th percentile of the distribution of acute sensitivity of species to pirimicarb for aquatic vertebrates. Results revealed values of 23.78 and 101.45mg/L pirimicarb as LC5096h for GS25 and GS36 tadpoles, respectively. The most evident effects were related with the swimming activity with NOEC and LOEC values within the 0.005-0.39mg/L pirimicarb concentration range. Aficida® induced DNA damage at the chromosomal level by increasing micronuclei frequency and other nuclear abnormalities, i.e., lobbed and notched nuclei and binucleated cells. Cellular cytotoxicity was found after Aficida® treatment. The presence of abdominal oedemas in exposed organisms and thus flotation response of organisms could be proposed as a new sensitive exposure parameter. The multiple end point assessment approach used allowed a complete understanding the multi level of effects occurring by exposure to pirimicarb, at least in B. pulchella.
Asunto(s)
Carbamatos/toxicidad , Daño del ADN , Insecticidas/toxicidad , Larva/efectos de los fármacos , Pirimidinas/toxicidad , Contaminantes Químicos del Agua/toxicidad , Animales , Anuros , Relación Dosis-Respuesta a Droga , Larva/genética , Dosificación Letal Mediana , Natación , Pruebas de Toxicidad Aguda , Pruebas de Toxicidad SubagudaRESUMEN
Abstract Presence of the relatively new sulfonylurea herbicide monosulfuron-ester at 0.03-300 nmol/L affected the growth of two non-target nitrogen-fixing cyanobacteria (Anabaena flos-aquae and Anabaena azotica) and substantially inhibited in vitro Acetolactate synthase activity, with IC50 of 3.3 and 101.3 nmol/L for A. flos-aquae and A. azotica, respectively. Presenting in 30-300 nmol/L, it inhibited protein synthesis of the cyanobacteria with less amino acids produced as its concentration increased. Our findings support the view that monosulfuron-ester toxicity in both nitrogen-fixing cyanobacteria is due to its interference with protein metabolism via inhibition of branch-chain amino acid biosynthesis, and particularly Acetolactate synthase activity.
Asunto(s)
Pirimidinas/toxicidad , Compuestos de Sulfonilurea/toxicidad , Anabaena/efectos de los fármacos , Anabaena/metabolismo , Dolichospermum flos-aquae/efectos de los fármacos , Dolichospermum flos-aquae/metabolismo , Ésteres/toxicidad , Herbicidas/toxicidad , Fijación del Nitrógeno/efectos de los fármacos , Anabaena/genética , Dolichospermum flos-aquae/genética , Aminoácidos/metabolismo , Nitrógeno/metabolismoRESUMEN
Presence of the relatively new sulfonylurea herbicide monosulfuron-ester at 0.03-300nmol/L affected the growth of two non-target nitrogen-fixing cyanobacteria (Anabaena flos-aquae and Anabaena azotica) and substantially inhibited in vitro Acetolactate synthase activity, with IC50 of 3.3 and 101.3nmol/L for A. flos-aquae and A. azotica, respectively. Presenting in 30-300nmol/L, it inhibited protein synthesis of the cyanobacteria with less amino acids produced as its concentration increased. Our findings support the view that monosulfuron-ester toxicity in both nitrogen-fixing cyanobacteria is due to its interference with protein metabolism via inhibition of branch-chain amino acid biosynthesis, and particularly Acetolactate synthase activity.
Asunto(s)
Anabaena/efectos de los fármacos , Anabaena/metabolismo , Dolichospermum flos-aquae/efectos de los fármacos , Dolichospermum flos-aquae/metabolismo , Ésteres/toxicidad , Herbicidas/toxicidad , Fijación del Nitrógeno/efectos de los fármacos , Pirimidinas/toxicidad , Compuestos de Sulfonilurea/toxicidad , Aminoácidos/metabolismo , Anabaena/genética , Dolichospermum flos-aquae/genética , Nitrógeno/metabolismoRESUMEN
Malaria remains one of the most serious global infectious diseases. An important target for antimalarial chemotherapy is the enzyme dihydroorotate dehydrogenase from Plasmodium falciparum (PfDHODH), which is responsible for the conversion of dihydroorotate to orotate in the de novo pyrimidine biosynthetic pathway. In this study, we have designed and synthesized fifteen 7-arylpyrazolo[1,5-a]pyrimidine derivatives using ring bioisosteric replacement and molecular hybridization of functional groups based on the highly active 5-methyl-N-(naphthalen-2-yl)-2-(trifluoromethyl)- [1,2,4]triazolo[1,5-a]pyrimidin-7-amine. The compounds were tested against Plasmodium falciparum, as antimalarials in mice with P. berghei, and as inhibitors of PfDHODH. Thirteen compounds were found to be active against P. falciparum, with IC50 values ranging from 1.2 ± 0.3 to 92 ± 26 µM in the anti-HRP2 and hypoxanthine assays. Four compounds showed the highest selective index (SI), which is a ratio between cytotoxicity and activity in vitro. The inhibition of PfDHODH showed that compound 30 (R2 = CH3; R5 = CF3; Ar = 7-ß-naphthyl) displayed higher and selective inhibitory activity, with IC50 = 0.16 ± 0.01 µM, followed by 25 (R2 = CH3; R5 = CH3; Ar = 7-ß-Naphthyl) and 19 (R2 = CF3; R5 = CF3; Ar = 7-ß-naphthyl), with IC50 = 4 ± 1 µM and 6 ± 1 µM, respectively. The trifluoromethyl group at the 2- or 5-positions of the pyrazolo[1,5-a]pyrimidine ring led to increased drug activity. The docking results agreed with the values obtained from enzymatic assays.
Asunto(s)
Antimaláricos/farmacología , Inhibidores Enzimáticos/farmacología , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/antagonistas & inhibidores , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/enzimología , Pirimidinas/química , Pirimidinas/farmacología , Animales , Antimaláricos/química , Antimaláricos/metabolismo , Antimaláricos/toxicidad , Línea Celular , Dihidroorotato Deshidrogenasa , Evaluación Preclínica de Medicamentos , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/metabolismo , Inhibidores Enzimáticos/toxicidad , Humanos , Ratones , Simulación del Acoplamiento Molecular , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/química , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/metabolismo , Conformación Proteica , Pirimidinas/metabolismo , Pirimidinas/toxicidadRESUMEN
We analyzed the aspects of lethality, genotoxicity, and cytotoxicity in the ten spotted live-bearer exposed under laboratory conditions to the pirimicarb-based formulation Patton Flow® (50% active ingredient (a.i.)). Acute effects were evaluated using different end points for lethality, genotoxicity, and cytotoxicity. Median lethal concentration (LC50) estimation was employed as a bioassay for lethality, whereas micronucleus (MN) induction and alterations in erythrocyte/erythroblast frequency were used as end points for genotoxicity and cytotoxicity, respectively. Results demonstrated an LC5096h value of 88 mg/L. Patton Flow® increased the MN frequency in fish erythrocytes after 48 h of exposure at a concentration of 66 mg/L, whereas a concentration range of 22-66 mg/L was able to exert the same genotoxic effect at 96 h of treatment. Furthermore, cytotoxicity was also observed by alterations in erythrocyte/erythroblast frequencies within the concentration range of 22-66 mg/L, regardless of the exposure time. Our current observations provide evidence that Patton Flow® (50% a.i.) should be considered a clear lethal, cytotoxic, and genotoxic agent on Cnesterodon decemmaculatus. Thus, repeated applications of this carbamic insecticide can enter the aquatic environment and exert deleterious effects on aquatic organisms other than the evaluated species C. decemmaculatus.
Asunto(s)
Carbamatos/toxicidad , Ciprinodontiformes , Daño del ADN/efectos de los fármacos , Insecticidas/toxicidad , Pirimidinas/toxicidad , Animales , Eritrocitos/efectos de los fármacos , Agua Dulce , Dosificación Letal Mediana , Pruebas de MicronúcleosRESUMEN
Among the search for new types of pesticides, the fungicide azoxystrobin (AZX) was the first patent of the strobilurin compounds, entering in the market in 1996. Its use worldwide is growing, mainly linked to soybean production, although its effects in non-target organisms are almost unknown. The goal of the present work was to evaluate effects of short-term AZX exposure to the aquatic macrophyte Myriophyllum quitense, focusing on oxidative stress parameters and DNA fragmentation. Significant inhibition of the antioxidant enzyme systems were observed at 50 µg/L AZX for catalase and peroxidase (p < 0.05). Lipid and DNA damage were significant at 50 and 100 µg/L AZX. These biomarkers were sensitive to AZX and can be used in a battery to evaluate the occurrence of AZX in freshwater ecosystems.
Asunto(s)
Fragmentación del ADN , Fungicidas Industriales/toxicidad , Metacrilatos/toxicidad , Estrés Oxidativo/efectos de los fármacos , Plantas/efectos de los fármacos , Pirimidinas/toxicidad , Contaminantes Químicos del Agua/toxicidad , Ensayo Cometa , Monitoreo del Ambiente/métodos , Peroxidación de Lípido/efectos de los fármacos , Plantas/genética , Plantas/metabolismo , EstrobilurinasRESUMEN
1. The present work investigated the pharmacokinetic and tissue distribution as well as acute toxicity of a new chemical entity (NCE), the anticancer candidate LaSOM 65 in Wistar rats. 2. LaSOM 65 pharmacokinetics was investigated after intravenous (i.v., 1 mg/kg) and oral (p.o., 10 and 30 mg/kg) dosing. Tissue distribution was assessed after i.v. bolus dose. Acute toxicity was evaluated after i.v. (1, 2.5 and 5 mg/kg) and p.o. (50, 100 and 150 mg/kg) administration. 3. Short half-life (1.75 ± 0.71 h), a clearance of 0.85 ± 0.18 L/h/kg and a volume of distribution of 1.76 ± 0.24 L/kg were observed after i.v. dosing. The compound showed good bioavailability and linear pharmacokinetics after oral doses. The NCE distributes consistently in lung and fatty tissues, with penetration ratios of 2.7 and 1.4, respectively. The other tissues investigated presented smaller penetration ratios. Adverse clinical symptoms were observed only after i.v. administration, and regressed 3 h after dosing. Compared with controls, no statistical differences were found for serum analysis, body weight and relative organ weight, indicating no acute toxicological effects. 4. Overall, LaSOM 65 showed good pharmacokinetic characteristics and no signs of acute toxicity, indicating that it is a promising anticancer candidate.
Asunto(s)
Antineoplásicos/farmacocinética , Antineoplásicos/toxicidad , Pirimidinas/farmacocinética , Pirimidinas/toxicidad , Tionas/farmacocinética , Tionas/toxicidad , Tejido Adiposo/metabolismo , Administración Intravenosa , Administración Oral , Análisis de Varianza , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Disponibilidad Biológica , Evaluación Preclínica de Medicamentos , Semivida , Pulmón/metabolismo , Masculino , Estructura Molecular , Pirimidinas/administración & dosificación , Pirimidinas/química , Ratas , Ratas Wistar , Tionas/administración & dosificación , Tionas/química , Distribución Tisular , Pruebas de Toxicidad AgudaRESUMEN
The ability of two 48 percent chlorpyrifos-based insecticides (Lorsban* 48E® and CPF Zamba®), two 50 percent pirimicarb-based insecticides (Aficida® and Patton Flow®), and two 48 percent glyphosate-based herbicides (Panzer® and Credit®) to induce DNA single-strand breaks in peripheral blood erythrocytes of Cnesterodon decemmaculatus (Jenyns, 1842) (Pisces, Poeciliidae) exposed under laboratory conditions was evaluated by the single-cell gel electrophoresis (SCGE) assay. In those fish exposed to Lorsban* 48E®, CPF Zamba®, Aficida®, Patton Flow®, Credit®, and Panzer®, a significant increase of the genetic damage was observed for all formulations regardless of the harvesting time. This genotoxic effect was achieved by an enhancement of Type II-IV comets and a concomitant decrease of Type 0-I comets over control values. A regression analysis revealed that the damage varied as a negative function of the exposure time in those Lorsban* 48E®- and Aficida®-treated fish. On the other hand, a positive correlation between damage increase and exposure time was achieved after Patton Flow® and Credit® treatment. Finally, no correlation was observed between increase in the genetic damage and exposure time after treatment with CPF Zamba® or Panzer®. These results highlight that all agrochemicals inflict primary genotoxic damage at the DNA level at sublethal concentrations, regardless of the exposure time of the aquatic organisms under study, at least within a period of 96 h of treatment.
Asunto(s)
Carbamatos/toxicidad , Cloropirifos/toxicidad , Roturas del ADN de Cadena Simple , Glicina/análogos & derivados , Herbicidas/toxicidad , Insecticidas/toxicidad , Poecilia/sangre , Pirimidinas/toxicidad , Animales , Bioensayo , Ensayo Cometa , Eritrocitos/efectos de los fármacos , Eritrocitos/ultraestructura , Glicina/toxicidad , Poecilia/genética , GlifosatoRESUMEN
The toxicity of six insecticides was determined for the peach-potato aphid, Myzus persicae (Hemiptera: Aphididae), and some of its natural enemies - the predatory beetles Cycloneda sanguinea (Coccinellidae) and Acanthinus sp. (Anthicidae), and the wasp parasitoid Diaeretiella rapae (Aphidiidae). Natural enemies from these groups are important natural biological control agents in a number of agroecosystems, and insecticides potentially safe to these non-target organisms should be identified using standardized tests. Thus, concentration-mortality bioassays were carried out with both the aphid and its natural enemies to assess the toxicity and selectivity of acephate, deltamethrin, dimethoate, methamidophos, methyl parathion, and pirimicarb. The latter insecticide was highly selective to all natural enemies tested, and its LC(90) for M. persicae was 14-fold lower than the field rate recommended for control of the aphid in brassica crops. Methyl parathion also showed selectivity to C. sanguinea and Acanthinus sp., but not to D. rapae. Acephate was the least potent insecticide against M. persicae and was equally or more toxic to the natural enemies relative to the aphid. Pirimicarb and methyl parathion were efficient against M. persicae and selective in favor of two of the natural enemies tested. Acanthinus sp. and C. sanguinea were more tolerant to the insecticides than was the parasitoid D. rapae. This study shows that there are selective insecticides that may be compatible with conservation of natural enemies in brassica crops, which is important practical information to improve integrated pest management systems in these crops.
Asunto(s)
Áfidos/efectos de los fármacos , Insecticidas/toxicidad , Animales , Carbamatos/toxicidad , Escarabajos/efectos de los fármacos , Dimetoato/toxicidad , Metil Paratión/toxicidad , Nitrilos/toxicidad , Compuestos Organotiofosforados/toxicidad , Control Biológico de Vectores , Fosforamidas , Piretrinas/toxicidad , Pirimidinas/toxicidad , Avispas/efectos de los fármacosRESUMEN
An activating mutation (V617F) in the pseudokinase domain of the Janus kinase (JAK)-2 tyrosine kinase has been described in 90% of patients with polycythemia vera (PV) and 50% of patients with essential thrombocythemia (ET) and primary myelofibrosis (MF). The discovery of JAK2V617F stirred the development of JAK2 inhibitors for treatment of patients with MF, ET and PV. Similar to other tyrosine kinase (TK) inhibitors in current use, JAK2 inhibitors target the adenosine triphosphate (ATP) binding site at the TK domain and not the pseudokinase domain, thus affecting both mutated and wild-type kinases. In fact, clinical trials of these compounds have demonstrated improvements in constitutional symptoms and splenomegaly in patients with both mutated and wild-type JAK2 MF. It is believed that these drugs may act not only through inhibition of neoplastic cell proliferation, but also by downregulating signaling through proinflammatory cytokine receptors. In this article, we review the current state of JAK2 inhibitors and discuss why these drugs could be a valuable addition to the treatment armamentarium for patients with and without the JAK2V617F mutation.
Asunto(s)
Janus Quinasa 2/antagonistas & inhibidores , Mutación Puntual , Mielofibrosis Primaria/tratamiento farmacológico , Mielofibrosis Primaria/enzimología , Inhibidores de Proteínas Quinasas/uso terapéutico , Animales , Benzamidas/uso terapéutico , Benzamidas/toxicidad , Citocinas/inmunología , Humanos , Imidazoles/uso terapéutico , Imidazoles/toxicidad , Janus Quinasa 2/química , Janus Quinasa 2/genética , Janus Quinasa 2/inmunología , Nitrilos , Mielofibrosis Primaria/genética , Mielofibrosis Primaria/inmunología , Inhibidores de Proteínas Quinasas/toxicidad , Pirazoles/uso terapéutico , Pirazoles/toxicidad , Piridazinas/uso terapéutico , Piridazinas/toxicidad , Pirimidinas/uso terapéutico , Pirimidinas/toxicidad , Pirrolidinas/uso terapéutico , Pirrolidinas/toxicidad , Sulfonamidas/uso terapéutico , Sulfonamidas/toxicidadRESUMEN
The carcinogenic biomarker aflatoxin B(1)-formamidopyrimidine 2,3-dihydro-2-(N-formyl)-2',5',6'-triamino-4'-4'-oxy-N-pyrimidyl-3-hydroxy-AFB(1) called AFB(1)-FAPY adduct, and Human Papilloma Virus (HPV) types 16 and 18 were quantified from DNA cervical scrapes from 40 women with cervical cancer (CC) and 14 healthy women as controls. The relationship between the AFB(1)-FAPY adduct and HPV types 16 and 18 was determined. Competitive inhibitory indirect ELISA was validated with 94% inhibition to quantify the AFB(1)-FAPY adducts in picograms per milligram of DNA (limit of detection = 0.1 pg/mg, and limit of quantification = 10 pg/mg), polymerase chain reaction and DNA sequencing to identify HPV types. The average concentration of AFB(1)-FAPY adducts/mg DNA in the CC cases was 1025 pg, 1420 pg with HPV16 and 630 pg sharing HPV18 (p = 0.03). In comparison, healthy controls had ≤ 2.6 pg/mg DNA, a statistically significant difference (p = 0.00006). The presence of AFB(1)-FAPY adduct increased six-fold the risk for CC between cases and controls, the odds ratio was 6.1 (95% CI = 1.4-25.4). There was a close relationship between the AFB(1)-FAPY adducts and HPV16 in CC samples.
Asunto(s)
Aflatoxina B1/química , Aflatoxina B1/toxicidad , Papillomavirus Humano 16/aislamiento & purificación , Papillomavirus Humano 18/aislamiento & purificación , Pirimidinas/química , Neoplasias del Cuello Uterino/epidemiología , Adulto , Anciano , Biomarcadores de Tumor/análisis , Estudios de Casos y Controles , Cromatografía Líquida de Alta Presión/métodos , Aductos de ADN , ADN Viral/efectos de los fármacos , ADN Viral/aislamiento & purificación , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Humanos , México/epidemiología , Persona de Mediana Edad , Pirimidinas/toxicidad , Reproducibilidad de los Resultados , Neoplasias del Cuello Uterino/virologíaRESUMEN
Cyprinus carpio were exposed under field conditions to 20.87 microg l(-1) of commercial herbicide bispyribac-sodium (Nominee, SC), during 7, 21 and 72 days. Enzymatic parameters such as catalase (CAT), glutathione S-transferase (GST) and acetylcholinesterase (AChE) activities, as well as thiobarbituric acid-reactive substances (TBARS) and protein carbonyl contents were studied in different tissues. After 7 days of exposure, GST activity decreased. At the same period, brain AChE activity increased, but a reduction of activity was observed in muscle tissue. Brain TBARS levels increased at 7 days. After 21 days of exposure liver CAT levels and muscle AChE activities decreased. In the same period, liver protein carbonyl and muscle TBARS increased. After 72 days of exposure in the field, AChE activity was reduced in both brain and muscle. Protein carbonyl contents in liver and brain TBARS levels increased. Muscle AChE activity, TBARS and protein carbonyl can be used as biomarkers of exposure to the herbicide bispyribac-sodium. This study demonstrates effects of exposure to bispyribac-sodium under rice field conditions on oxidative stress parameters in tissues of Cyprinus carpio.
Asunto(s)
Benzoatos/toxicidad , Biomarcadores/análisis , Carpas , Herbicidas/toxicidad , Estrés Oxidativo/efectos de los fármacos , Pirimidinas/toxicidad , Acetilcolinesterasa/metabolismo , Animales , Encéfalo/efectos de los fármacos , Encéfalo/enzimología , Encéfalo/metabolismo , Carpas/metabolismo , Catalasa/metabolismo , Femenino , Glutatión Transferasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/enzimología , Hígado/metabolismo , Masculino , Músculos/efectos de los fármacos , Músculos/enzimología , Músculos/metabolismo , Oryza/crecimiento & desarrollo , Carbonilación Proteica/efectos de los fármacos , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Pruebas de ToxicidadRESUMEN
The acute toxicity, genotoxicity, and cytotoxicity of the pirimicarb-containing commercial-formulation carbamate insecticide Aficida (50% pirimicarb) were evaluated on Cnesterodon decemmaculatus (Pisces, Poeciliidae) exposed under laboratory conditions. Micronucleus (MN) induction as well as alterations in the erythrocytes:erythroblasts ratios were employed as end-points for genotoxicity and cytotoxicity, respectively. Cr(VI) and cyclophosphamide were used as positive controls for the toxicity and geno-cytotoxicity assays, respectively. Mean values of 344.3 and 225.5mg Aficida(®)/L were determined for LC-50(24h) and LC-50(96h), respectively. In 48h-exposed fish, a MN increase was found in Aficida-treated fish in the 50-157mg/L concentration range. When fish were exposed to Aficida for 96h, only those animals treated at 50-100mg/L showed an increase in MN frequency. Cellular cytotoxicity, revealed by a decreased proportion of circulating erythrocytes and an enhancement of erythroblasts, was found after 48h of exposure in 50-157mg Aficida/L-treated fish, while, after 96h exposure, only 100-157mg Aficida/L induced the same effect. This species provides a useful experimental model for the biomonitoring of aquatic ecosystems.
Asunto(s)
Carbamatos/toxicidad , Insecticidas/toxicidad , Poecilia , Pirimidinas/toxicidad , Contaminantes Químicos del Agua/toxicidad , Animales , Biomarcadores/análisis , Pruebas de Micronúcleos/métodos , Mutágenos/toxicidad , Pruebas de Toxicidad AgudaRESUMEN
Pirimicarb and its formulation Aficida (50% pirimicarb) effects were studied on CHO-K1 cells employing sister chromatid exchange (SCE), chromosomal aberrations (CA), cell-cycle progression and mitotic index analyses. Continuous treatments were performed within 10-300 microg/ml concentration-range. Pirimicarb, but not Aficida, induced a concentration-dependent increase of abnormal cells. Pirimicarb induced a greater frequency of chromatid/isochromatid breaks than Aficida did. Regression analyses showed a concentration-dependent increase in the frequency of chromatid-type breaks for both compounds whereas only the frequency of isochromatid-type breaks did in those pirimicarb-treated cultures. SCEs in pirimicarb- or Aficida-treated cultures were significantly higher than control values with concentrations of 100-200 microg/ml. Both test compounds induced equivalent frequency of SCEs. A delay in cell-cycle kinetics was observed for pirimicarb and Aficida within 100-300 and 200-300 microg/ml concentration-range, respectively. An inhibition of MI was observed for both chemicals regardless of tested concentrations. Finally, the CAs appears to be a higher sensitive bioassay to detect DNA damage at lower concentrations of pirimicarb than SCEs does. The results demonstrated that pirimicarb and Aficida exert geno-cytotoxicity, at least in CHO-K1 cells.
Asunto(s)
Carbamatos/toxicidad , Aberraciones Cromosómicas , Insecticidas/toxicidad , Pirimidinas/toxicidad , Intercambio de Cromátides Hermanas , Animales , Células CHO , Cricetinae , Cricetulus , Relación Dosis-Respuesta a DrogaRESUMEN
Acute toxicity, genotoxicity, and cytotoxicity of the pirimicarb-containing commercial-formulation carbamate insecticide Aficida(R) (50% pirimicarb) were evaluated on Rhinella arenarum (Anura, Bufonidae) tadpoles exposed under laboratory conditions. Lethal and sublethal effects were employed as bioassays for acute toxicity, whereas micronuclei (MNi) induction and alterations in the ratio erythrocytes:erythroblasts were employed as end-points for genotoxicity and cytotoxicity, respectively. Cr(VI) (23 mg L(-1)) and cyclophosphamide (40 mg L(-1)) were employed as positive controls for toxicity and geno-cytotoxicity assays, respectively. In Gosner stage 25 (STD25), the results revealed mean values of 402.0 and 223.6 mg Aficida L(-1) for LC-50(24)(h) and LC-50(96)(h), respectively. When STD37-39 tadpoles were exposed, the LC-50(24)(h) and LC-50(96)(h) reached values of 239.4 and 181.7 mg Aficida L(-1), respectively. Sublethal effects revealed a mean EC-50(96)(h) of 133.85 and 104.2mg Aficida in those STD25 and STD37-39 treated tadpoles, respectively. The results demonstrated that in 48-h-exposed tadpoles, a MNi increase was found only in those 80.0 mg L(-1) Aficida-treated individuals. When tadpoles were exposed to Aficida for 96h, only the 160 mg L(-1)-treated individuals showed a significant increase in MNi frequency. Concentrations ranging from 80.0 to 250.0mg Aficida L(-1) resulted in cellular cytotoxicity, revealed by a decreased proportion of circulating erythrocytes and an enhancement of erythroblasts. Accordingly, this species could provide a suitable and useful experimental model for biomonitoring aquatic ecosystems.
Asunto(s)
Bufo arenarum/crecimiento & desarrollo , Carbamatos/toxicidad , Insecticidas/toxicidad , Pirimidinas/toxicidad , Animales , Ciclofosfamida/toxicidad , Citotoxinas/toxicidad , Eritroblastos/efectos de los fármacos , Eritrocitos/efectos de los fármacos , Larva/efectos de los fármacos , Dosificación Letal Mediana , Pruebas de Mutagenicidad , Pruebas de Toxicidad AgudaRESUMEN
We studied 103 consecutive patients with chronic myeloid leukaemia on treatment with imatinib (IM) and 57 patients with chronic myeloproliferative disorders not treated with IM in order to evaluate its cardiotoxicity. There was no statistical difference regarding cardiac symptoms and signs, BNP levels and echocardiographic measurements for IM and control groups, except for peripheral oedema, more frequent in the IM group. Four patients in the IM group presented a BNP level >100pg/ml, one of them with depressed LVEF. IM was not related to systematic deterioration of cardiac function, but there is still a possibility of isolated cases of cardiotoxicity.