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1.
Anal Chim Acta ; 1182: 338940, 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34602204

RESUMO

We develop an electrochemical sensor by using 2D-transition metal dichalcogenides (TMD), specifically MoS2, and nanoparticles stabilized with cucurbit[8]uril (CB[8]) incorporated together with them. Two different nanoparticles are assayed: diamond nanoparticles (DNPs) and gold nanoparticles (AuNp). 0D materials, together with TMD, provide increased conductivity and active surface while the macrocycle CB[8] affords selectivity towards the guest methyl viologen (MV2+), also named paraquat. Glassy Carbon (GC) electrodes are modified by drop-casting of suspensions of MoS2, followed by either a CB[8]-DNPs hybrid dispersion or a CB[8]-AuNp suspension. Atomic force microscopy is employed for the morphological characterization of the electrochemical sensor surface while cyclic voltammetry and electrochemical impedance spectroscopy techniques allow the electrochemical characterization of the sensor. The well-stablished signals of CB[8]-encapsulated MV2+ arise in voltammetric measurements when the macrocycle modifies the 0D-materials. Once the sensor construction and differential pulse voltammetry parameters have been optimized for quantification purposes, calibration procedures are performed with the platform GC/MoS2/CB[8]-DNPs. This sensing platform shows linear relations between peak intensity and the MV2+ concentration in the linear concentration range of (0.73-8.0) · 10-6 M with a limit of detection of 2.2 · 10-7 M. Analyses of river water samples fortified with MV2+ at the µM level shows recoveries of 100% with RSD values of 6.4% (n = 3).


Assuntos
Dissulfetos , Nanopartículas Metálicas , Hidrocarbonetos Aromáticos com Pontes , Ouro , Imidazóis , Paraquat
2.
Artigo em Chinês | MEDLINE | ID: mdl-34488273

RESUMO

Objective: To establish a LC-MS/MS method for determination of paraquat and diquat in plasma and urine samples. Methods: Plasma is precipitated by acetonitrile then diluent with phosphate buffer (pH=7) , urine is diluent with phosphate buffer (pH=7) , then diluent samples extracted with Oasis WCX solid-phase extraction column. Samples were analyzed using LC-MS/MS in multiple reaction monitoring (MRM) mode. The analytical column was XBridge®BEH-HILIC (100 mm×2.1 mm×2.5 µm) and the mobile phase were 100 mmol ammonium formate add 0.5% formic acid and acetonitrile. Paraquat was quantified by internal standard method and diquat by external standard method. Results: The calibration curves of paraquat and diquat were linear in the concentration range of 10.0~120.0 µg/L, the correlation coefficient (r) were 0.9985~0.9994. The limit of detection of paraquat in plasma and urine were 1.98 µg/L and 1.00 µg/L, respectively, the recovery rate were 100.2%~107.3%, the RSD were 1.6%~3.3%. The limit of detection of diquat in plasma and urine were 1.80 µg/L and 2.77 µg/L, respectively, the recovery rate were 85.3%~93.1%, the RSD were 1.8%~5.5%. Conclusion: This method is sensitive and accurate, and can simultaneously determine paraquat and diquat in plasma and urine.


Assuntos
Diquat , Paraquat , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Paraquat/análise , Extração em Fase Sólida , Espectrometria de Massas em Tandem
3.
J Int Med Res ; 49(9): 3000605211043243, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34525860

RESUMO

OBJECTIVE: Paraquat (PQ) is associated with high mortality rates in acute poisoning. This study aimed to determine the importance of the alveolar-arterial partial pressure difference (A-aDo2) in the expected consequences of acute PQ poisoning. METHODS: Patients who were hospitalized for PQ poisoning in 2018 were enrolled in this retrospective study. A-aDo2 data were collected. Multivariate analysis was performed using binary logistic regression to determine whether A-aDo2 is an independent risk factor for mortality from PQ. RESULTS: A total of 352 cases were analyzed. The mean PQ dose was 36.84 ± 50.30 mL (0.3-500 mL). There were 185 survivors and 167 non-survivors. The mean A-aDo2 was not significantly correlated between survivors and non-survivors on day 1. However, there were significant differences in A-aDo2 between survivors and non-survivors on days 3, 7, 14, and 21. Increased A-aDo2 values were correlated with an increased mortality rate. The mean A-aDo2 on day 14 showed the most significant difference between survivors and non-survivors. CONCLUSION: Our study suggests that A-aDo2 plays an important role as a reference index, which could be a useful predictor in assessing acute PQ poisoning, especially on the 14th day after onset of poisoning.


Assuntos
Pulmão , Paraquat , Humanos , Pressão Parcial , Estudos Retrospectivos , Fatores de Risco
4.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 33(8): 999-1002, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34590571

RESUMO

OBJECTIVE: To investigate the clinical values of the differences between hematocrit and serum albumin (HCT-ALB) for evaluating the severity of patients with acute paraquat (PQ) poisoning. METHODS: Patients with acute PQ poisoning admitted to the Second People's Hospital of Yunnan Province from January 2018 to December 2019 were enrolled, and healthy voluteers during the same period were selected as the control. The general information, poisoning dose and poisoning time of patients, as well as the HCT and serum ALB levels before blood product infusion, intravenous infusion, or hemopurification at admission were collected, and the HCT-ALB was calculated. According to the results of rapid semiquantitative test of PQ in urine at admission, the patients were divided into PQ low concentration group (0-10 mg/L) and PQ high concentration group (30-100 mg/L). The relationship between poisoning time, poisoning dose, HCT-ALB and the degree of acute PQ poisoning were analyzed, and Spearman method was used to analyze the grade correlation. RESULTS: A total of 295 patients with acute PQ poisoning were enrolled, including 118 cases in PQ low concentration group and 177 cases in PQ high concentration group, and another 200 healthy persons matched with PQ patients in gender and age (healthy control group). The poisoning time of PQ low concentration group was significantly longer than that of PQ high concentration group [hours: 11.0 (6.0, 60.0) vs. 8.0 (5.0, 20.5), P < 0.01], but the poisoning dose was significantly lower than that of PQ high concentration group [mL: 10.0 (5.8, 15.0) vs. 40.0 (20.0, 80.0), P < 0.01]. The HCT and HCT-ALB in PQ low and high concentration groups were significantly higher than those of the healthy control group [HCT: (43.14±4.41)%, (43.54±5.40)% vs. (42.14±2.15)%, HCT-ALB: 3.59±6.26, 5.94±7.80 vs. -7.26±3.55, all P < 0.01], but ALB was significantly lower than that of the healthy control group (g/L: 39.54±5.74, 37.60±7.15 vs. 49.40±3.41, both P < 0.01). With the increase of urine PQ concentration, the HCT and HCT-ALB further increased, and ALB further decreased. There were significant differences between PQ high concentration group and PQ low concentration group [HCT: (43.54±5.40)% vs. (43.14±4.41)%, HCT-ALB: 5.94±7.80 vs. 3.59±6.26, ALB (g/L): 37.60±7.15 vs. 39.54±5.74, all P < 0.05]. The poisoning severity of patients with acute PQ poisoning were negatively correlated with poisoning time and ALB (r values were -0.195 and -0.695, respectively, both P < 0.01), there were positively correlated with poisoning dose, HCT, and HCT-ALB (r values were 0.650, 0.256, 0.737, respectively, all P < 0.01), and the correlation between HCT-ALB and poisoning severity was the strongest. CONCLUSIONS: The HCT-ALB can reflect the poisoning severity of patients with acute PQ poisoning and indirectly reveal the pathological changes of microvessels in patients with acute PQ poisoning.


Assuntos
Paraquat , Envenenamento , China , Hematócrito , Humanos , Prognóstico , Albumina Sérica
5.
Analyst ; 146(20): 6270-6280, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34549734

RESUMO

We propose the fabrication of a novel ready-to-use electrochemical sensor based on a screen-printed graphene paste electrode (SPGrE) modified with platinum nanoparticles and coated with a molecularly imprinted polymer (PtNPs@MIP) for sensitive and cost-effective detection of paraquat (PQ) herbicide. Successive coating of the PtNPs surface with SiO2 and vinyl end-groups formed the PtNPs@MIP. Next, we terminated the vinyl groups with a molecularly imprinted polymer (MIP) shell. MIP was attached to the PtNPs cores using PQ as the template, methacrylic acid (MAA) as the monomer, ethylene glycol dimethacrylate (EGDMA) as the cross-linker, and 2,2'-azobisisobutyronitrile (AIBN) as the initiator. Coating the SPGrE surface with PtNPs@MIP furnished the PQ sensor. We studied the electrochemical mechanism of PQ on the MIP sensor using cyclic voltammetry (CV) experiments. The PQ oxidation current signal appears at -1.08 V and -0.71 V vs. Ag/AgCl using 0.1 M potassium sulfate solution. Quantitative analysis was performed by anodic stripping voltammetry (ASV) using a deposition potential of -1.4 V for 60 s and linear sweep voltammetric stripping. The MIP sensor provides linearity from 0.05 to 1000 µM (r2 = 0.999), with a lower detection limit of 0.02 µM (at -0.71 V). The compact imprinted sensor gave a highly sensitive and selective signal toward PQ. The ready-to-use MIP sensor can provide an alternative approach to the determination of paraquat residue on vegetables and fruits for food safety applications.


Assuntos
Grafite , Nanopartículas Metálicas , Impressão Molecular , Técnicas Eletroquímicas , Eletrodos , Polímeros Molecularmente Impressos , Paraquat , Platina , Dióxido de Silício
6.
Biosens Bioelectron ; 194: 113612, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34507094

RESUMO

We have reported an optical indicator displacement assay (IDA) for heparin with a UV-vis absorbance and fluorescence dual-readout based on pyranine/methyl viologen (MV2+). Upon introducing heparin, pyranine/MV2+ shows a clearly observable increase in UV-vis absorbance and a turn-on of the fluorescence signal. We have demonstrated that the ionic nature of buffers significantly affects the pyranine displacement and the zwitterionic HEPES was most suitable for heparin sensing. After careful screening of experimental conditions, the pyranine/MV2+-based optical chemosensor exhibits a fast, sensitive, and selective response toward heparin. It shows dynamic linear concentration of heparin in the ranges of 0.1-40 U·mL-1 and 0.01-20 U·mL-1 for the absorptive and fluorescent measurements, respectively, which both cover the clinically relevant levels of heparin. As with the animal experiments, the optical chemosensor has been demonstrated to be selective and effective for heparin level qualification in rat plasma. The chemosensor is readily accessible, cost-effective, and reliable, which holds a great promise for potential application on clinical and biological studies. Furthermore, this IDA system can serve as an IMPLICATION logic gate with a reversible and switchable logical manner.


Assuntos
Técnicas Biossensoriais , Heparina , Animais , Sulfonatos de Arila , Corantes Fluorescentes , Paraquat , Ratos
7.
Ecotoxicol Environ Saf ; 223: 112571, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34352584

RESUMO

The present study investigates whether paraquat (PQ) regulates polarization of alveolar macrophages through glycolysis and promotes the occurrence of acute lung injury in rats. In vivo, the PQ intraperitoneal injection was used to construct a model of acute lung injury in rats. In vitro, the study measured the effect of different concentrations of PQ on the viability of the alveolar macrophages, and explored the polarization and glycolysis metabolism of alveolar macrophages at different time points after PQ intervention. Compared with the normal control (NC) group, the lung pathological damage in rats increased gradually after PQ poisoning, reaching a significant degree at 48 h after poisoning. The PQ-poisoned rat serum showed increased expressions of interleukin-6 (IL-6), tumor necrosis factor- α (TNF-α), and M1 macrophage marker, iNOS, while the expression of interleukin-10 (IL-10) and M2 macrophage marker, Arg1, decreased. The toxic effect of PQ on alveolar macrophages was dose- and time-dependent. Compared with the NC group, IL-6 and TNF-α in the cell supernatant gradually increased after PQ intervention, while the IL-10 content gradually decreased. The PQ intervention in alveolar macrophages increased the expression of intracellular glycolysis rate-limiting enzyme pyruvate kinase isozymes M1/M2 (PKM1/M2), lactate, lactate/pyruvate ratio, and the polarization of alveolar macrophage towards M1. Inhibition of cellular glycolysis significantly reduced the PQ-induced alveolar macrophage polarization to M1 type. Thus, PQ induced increased polarization of lung macrophages toward M1 and decreased polarization toward M2, promoting acute lung injury. Therefore, it can be concluded that PQ regulates the polarization of alveolar macrophages through glycolysis.


Assuntos
Lesão Pulmonar Aguda , Paraquat , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Glicólise , Pulmão/metabolismo , Macrófagos Alveolares/metabolismo , Paraquat/toxicidade , Ratos , Fator de Necrose Tumoral alfa/metabolismo
8.
Pestic Biochem Physiol ; 178: 104919, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34446195

RESUMO

BACKGROUND: Paraquat poisoning leads to lung injury and pulmonary fibrosis. The effect of paraquat encapsulation by previously described Pectin/Chitosan/Tripolyphosphate nanoparticles on its pulmonary toxicity was investigated in present study in a rat model of poison inhalation. MATERIAL AND METHOD: The rats inhaled nebulized different formulation of paraquat (n = 5) for 30 min in various experimental groups. Lung injury and fibrosis scores, Lung tissue enzymatic activities, apoptosis markers were determined compared among groups. RESULTS: Encapsulation of paraquat significantly rescued both lung injury and fibrosis scores. Lung MDA level was reduced by encapsulation. Paraquat poisoning led to lung tissue apoptosis as was evidenced by higher Caspase-3 and Bax/Bcl2 expressions in rats subjected to paraquat inhalation instead of normal saline or free nanoparticles. Again, nanoencapsulation reduced these apoptosis markers significantly. Alpha-SMA expression was also reduced by encapsulation. Nanoparticles per se have no or little toxicity as was evidenced by inflammatory and apoptotic markers and histological scores. CONCLUSION: In a rat model of inhalation toxicity of paraquat, loading of this herbicide on PEC/CS/TPP nanoparticles reduced acute lung injury and fibrosis. The encapsulation also led to lower apoptosis, oxidative stress and alpha-SMA expression in the lung tissue.


Assuntos
Quitosana , Paraquat , Animais , Apoptose , Fibrose , Pulmão/patologia , Paraquat/toxicidade , Pectinas , Polifosfatos , Ratos
9.
Pestic Biochem Physiol ; 178: 104944, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34446210

RESUMO

Maneb (MB)- and paraquat (PQ)-induced oxidative stress in rat polymorphonuclear leukocytes (PMNs) is regulated in parallel by cytochrome P450 2E1 (CYP2E1) and inducible nitric oxide synthase (iNOS). However, mechanism underlying their regulation is not yet understood. The study investigated the role of nuclear factor- kappa B (NF-κB) and mitogen-activated protein kinase/extracellular signal regulated kinase/protein kinase C (MEK/ERK/PKC) pathway in the regulation of iNOS- and CYP2E1-induced oxidative stress in PMNs. MB + PQ-induced changes in nitrite content, lipid peroxidation (LPO), iNOS expression/activity and inflammatory mediators were alleviated by aminoguanidine (AG), an iNOS inhibitor, without any change in CYP2E1. Alternatively, diallyl sulphide (DAS), a CYP2E1 inhibitor, rescued from MB + PQ-induced changes in CYP2E1 activity/expression, free radical generation, superoxide dismutase (SOD) activity, LPO and pro-inflammatory cytokines without any alterations in nitrite content and iNOS activity/expression. Pyrrolidine dithiocarbamate (PDTC), NF-κB inhibitor, did not alter CYP2E1 but mitigated free radical generation, SOD activity, LPO, nitrite content, iNOS activity/expression and levels of pro-inflammatory cytokines (tumor necrosis factor-α, interleukine-1ß and interleukine-4). Ex-vivo treatment with MEK inhibitor (PD98059), ERK1/2 inhibitor (AG126) or PKC inhibitor (rottlerin) ameliorated MB + PQ-induced increase in free radical generation and CYP2E1 activity/expression in PMNs. While PD98059 and AG126 abated MB + PQ-induced increase in ERK1/2, PKC-α/δ and CYP2E1 levels, rottlerin restored PKC-α/δ and CYP2E1 towards normalcy without affecting ERK1/2 level in MB + PQ-treated group. The results suggest that iNOS and CYP2E1 contributing to MB + PQ-induced oxidative stress in rat PMNs exhibit differential regulatory mechanisms. The inflammatory mediators regulate iNOS expression while CYP2E1 expression is triggered via MEK-ERK1/2-PKC pathway.


Assuntos
Maneb , Animais , Citocromo P-450 CYP2E1/metabolismo , NF-kappa B , Neutrófilos/metabolismo , Óxido Nítrico , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo , Paraquat/toxicidade , Ratos
10.
Nat Commun ; 12(1): 4336, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34267196

RESUMO

Glutathione (GSH) is the most abundant cellular antioxidant. As reactive oxygen species (ROS) are widely believed to promote aging and age-related diseases, and antioxidants can neutralize ROS, it follows that GSH and its precursor, N-acetyl cysteine (NAC), are among the most popular dietary supplements. However, the long- term effects of GSH or NAC on healthy animals have not been thoroughly investigated. We employed C. elegans to demonstrate that chronic administration of GSH or NAC to young or aged animals perturbs global gene expression, inhibits skn-1-mediated transcription, and accelerates aging. In contrast, limiting the consumption of dietary thiols, including those naturally derived from the microbiota, extended lifespan. Pharmacological GSH restriction activates the unfolded protein response and increases proteotoxic stress resistance in worms and human cells. It is thus advantageous for healthy individuals to avoid excessive dietary antioxidants and, instead, rely on intrinsic GSH biosynthesis, which is fine-tuned to match the cellular redox status and to promote homeostatic ROS signaling.


Assuntos
Acetilcisteína/farmacologia , Envelhecimento/efeitos dos fármacos , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/fisiologia , Glutationa/farmacologia , Envelhecimento/genética , Envelhecimento/fisiologia , Animais , Animais Geneticamente Modificados , Proteínas de Caenorhabditis elegans/genética , Proteínas de Ligação a DNA/genética , Suplementos Nutricionais , Escherichia coli , Feminino , Fibroblastos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Glutationa/metabolismo , Humanos , Masculino , Paraquat/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Compostos de Sulfidrila/metabolismo , Fatores de Transcrição/genética , Resposta a Proteínas não Dobradas/fisiologia
11.
Artigo em Chinês | MEDLINE | ID: mdl-34218561

RESUMO

Objective: To investigate the mechanism of diallyl sulfide (DAS) on paraquat (PQ) - induced acute lung injury in rats. Methods: In May 2016, 32 adult male Wistar rats were randomly divided into control group, model (PQ) group, DAS treatment group and dexamethasone (DXM) treatment group, with 8 rats in each group. PQ poisoning model was established by intragastric administration of PQ solution (70 mg/kg) . 100 mg/kg DAS (DAS treatment group) , normal saline (control group and PQ group) and 1 mg/kg DXM (DXM treatment group) were injected intraperitoneally before and after modeling. After 24 hours, the rats were killed and the degree of lung injury was observed. The expression of inducible nitric oxide synthase (iNOS) in lung tissue was measured. Alveolar macrophages were isolated and cultured. The supernatant was taken to determine the content of NO, and the expressions of iNOS mRNA in alveolar macrophages were detected. Results: Compared with the control group, the pathological injury score and the expression of iNOS in the lung tissue of PQ group were significantly increased, and the content of NO secreted by alveolar macrophages and the expression of iNOS mRNA were significantly increased (P<0.05) . Compared with PQ group, the pathological injury scores and the expressions of iNOS in lung tissue of rats in DAS treatment group and DXM treatment group were significantly decreased, and the contents of NO secreted by alveolar macrophages and the expressions of iNOS mRNA were significantly decreased (P<0.05) . There was no significant difference between DXM group and DAS group (P>0.05) . Conclusion: DAS may have protective effect on acute lung injury induced by PQ in rats.


Assuntos
Paraquat , Venenos , Compostos Alílicos , Animais , Pulmão , Masculino , Paraquat/farmacologia , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Sulfetos
12.
Molecules ; 26(12)2021 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-34199157

RESUMO

The influence of p-terphenyl polyketides 1-3 from Aspergillus candidus KMM 4676 and cerebroside flavuside B (4) from Penicillium islandicum (=Talaromyces islandicus) against the effect of neurotoxins, rotenone and paraquat, on Neuro-2a cell viability by MTT and LDH release assays and intracellular ROS level, as well as DPPH radical scavenging activity, was investigated. Pre-incubation with compounds significantly diminished the ROS level in rotenone- and paraquat-treated cells. It was shown that the investigated polyketides 1-3 significantly increased the viability of rotenone- and paraquat-treated cells in two of the used assays but they affected only the viability of paraquat-treated cells in the LDH release assay. Flavuside B statistically increased the viability of paraquat-treated cells in both MTT and LDH release assays, however, it increased the viability of rotenone-treated cells in the LDH release assay. Structure-activity relationships for p-terphenyl derivatives, as well as possible mechanisms of cytoprotective action of all studied compounds, were discussed.


Assuntos
Aspergillus/química , Citoproteção/efeitos dos fármacos , Glicoesfingolipídeos/farmacologia , Neuroblastoma/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Neurotoxinas/toxicidade , Policetídeos/farmacologia , Animais , Linhagem Celular Tumoral , Sobrevivência Celular , Herbicidas/toxicidade , Inseticidas/toxicidade , Camundongos , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Fármacos Neuroprotetores/química , Paraquat/toxicidade , Policetídeos/química , Espécies Reativas de Oxigênio , Rotenona/toxicidade
13.
Toxicol Appl Pharmacol ; 426: 115636, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34214573

RESUMO

Paraquat (PQ), an herbicide widely used in agriculture, is considered a highly toxic compound. In hepatocytes, P-glycoprotein (P-gp/Abcb1) is a canalicular transporter involved in PQ extrusion from the cell. Previously, we demonstrated that genistein (GNT) induces P-gp in rat liver. In this study, the protective role of GNT pretreatment towards hepatic damage in a model of acute intoxication with PQ in rats, was investigated. Wistar rats were randomized in 4 groups: Control, GNT (5 mg/kg/day sc, 4 days), PQ (50 mg/kg/day ip, last day) and GNT+ PQ. Hepatic lipoperoxidation (LPO) was evaluated by the thiobarbituric acid reactive substances method. Hepatic levels of 4-hydroxynonenal protein adducts (4-HNEp-add) and glutathione-S-transferase alpha (GSTα) protein expression were evaluated by Western blotting. Hepatic glutathione levels and plasma levels of alanine transaminase (ALT) and aspartate transaminase (AST) were also measured. Biliary excretion of PQ was studied in vivo and in isolated perfused liver. PQ was quantified by HPLC. PQ significantly increased AST and ALT activities, malondialdehyde and 4-HNEp-add levels, whereby pretreatment with GNT ameliorated this effect. PQ biliary excretion remained unchanged after treatments in both experimental models. Hepatic GSTα expression was augmented in GNT group. GNT pretreatment increased hepatic glutathione levels in PQ + GNT group. These results agree with the lower content of 4-HNEp-adds in GNT + PQ group respect to PQ group. Unexpectedly, increased activity of P-gp did not enhance PQ biliary excretion. Thus, GNT protective mechanism is likely through the induction of GSTα which results in increased 4-HNE metabolism before formation of protein adducts.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Genisteína/uso terapêutico , Substâncias Protetoras/uso terapêutico , Alanina Transaminase/sangue , Aldeídos/metabolismo , Animais , Aspartato Aminotransferases/sangue , Bile/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Genisteína/farmacologia , Glutationa/metabolismo , Glutationa Transferase/metabolismo , Herbicidas , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Paraquat , Substâncias Protetoras/farmacologia , Ratos Wistar
14.
J Phys Chem B ; 125(30): 8539-8549, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34313435

RESUMO

This paper reports the self-assembly of a donor-acceptor system into nanoscopic structures and the photo processes taking place within these structures. The donor employed is pyrene linked to two ß-cyclodextrin molecules (CD-PY-CD), and adamantane-linked methyl viologen attached to the three arms of mesitylene (Ms-(MV2+-AD)3) is the acceptor. CD-PY-CD and Ms-(MV2+-AD)3 when dissolved in water self-assembled into vesicles, which joined together to give long fibers. The self-assembly was studied using spectroscopic and microscopic techniques. Fluorescence of the pyrene chromophore was quenched within the self-assembled system due to efficient photoinduced electron transfer to methyl viologen. Photoinduced electron transfer within the assembly is confirmed through identification of product radical ions in flash photolysis experiments. Steady-state irradiation of the self-assembled system in an optical bench led to the formation of methyl viologen radical cation, which was stable for a few hours. Longevity of the radical cation was attributed to the fast reaction of pyrene radical cation with adjacent pyrene to give an unstable adduct, which slows down the back electron transfer process.


Assuntos
Paraquat , Pirenos , Transporte de Elétrons , Fotoquímica , Viologênios
15.
Int J Mol Sci ; 22(11)2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34205973

RESUMO

The Arabidopsis AtCRK5 protein kinase is involved in the establishment of the proper auxin gradient in many developmental processes. Among others, the Atcrk5-1 mutant was reported to exhibit a delayed gravitropic response via compromised PIN2-mediated auxin transport at the root tip. Here, we report that this phenotype correlates with lower superoxide anion (O2•-) and hydrogen peroxide (H2O2) levels but a higher nitric oxide (NO) content in the mutant root tips in comparison to the wild type (AtCol-0). The oxidative stress inducer paraquat (PQ) triggering formation of O2•- (and consequently, H2O2) was able to rescue the gravitropic response of Atcrk5-1 roots. The direct application of H2O2 had the same effect. Under gravistimulation, correct auxin distribution was restored (at least partially) by PQ or H2O2 treatment in the mutant root tips. In agreement, the redistribution of the PIN2 auxin efflux carrier was similar in the gravistimulated PQ-treated mutant and untreated wild type roots. It was also found that PQ-treatment decreased the endogenous NO level at the root tip to normal levels. Furthermore, the mutant phenotype could be reverted by direct manipulation of the endogenous NO level using an NO scavenger (cPTIO). The potential involvement of AtCRK5 protein kinase in the control of auxin-ROS-NO-PIN2-auxin regulatory loop is discussed.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Ácidos Indolacéticos/metabolismo , Proteínas Serina-Treonina Quinases/genética , Receptores de Superfície Celular/genética , Arabidopsis/crescimento & desenvolvimento , Transporte Biológico/genética , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Gravitação , Gravitropismo/genética , Peróxido de Hidrogênio/farmacologia , Meristema/genética , Meristema/crescimento & desenvolvimento , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Paraquat/farmacologia , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismo
16.
Vet Q ; 41(1): 217-225, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34223806

RESUMO

BACKGROUND: Paraquat (1,1-dimethyl-4,4-bipyridinium dichloride) is a toxic herbicide. Accidental ingestion of paraquat in animals and humans causes respiratory failure and death. AIM: To describe the radiographic features of confirmed paraquat intoxication in a group of dogs and determines whether any identified features can facilitate this diagnosis. METHODS: Eleven dogs diagnosed with paraquat intoxication were selected from two institutions between November 2014 and August 2019 comprising five males (all intact) and six females (one intact and five spayed). The mean age was 3.9 ± 2.9 (SD) years and their mean weight was 11.6 ± 5.0 kg. The tentative diagnosis was confirmed through analysis of their urine samples using a colorimetric assay (paraquat concentation 0.39 µg/ml ranging from 0.19-0.65 µg/ml), and their clinical signs were reviewed. Thoracic radiographs were evaluated for the presence of pneumomediastinum, lung patterns (interstitial or alveolar) and their locations (caudodorsal, cranioventral, diffuse, or symmetrical), subcutaneous emphysema, pneumoretroperitoneum, and pneumothorax. RESULTS: The most common clinical signs were dyspnea (11/11, 100%) and anorexia (9/11, 82%). Pneumomediastinum (10/11, 91%) and symmetrically increased lung opacity (7/11, 65%) were the most common radiographic features. Pneumothorax (3/11, 27%), pleural effusion (3/11, 27%), subcutaneous emphysema (2/11, 18%), and pneumoretroperitoneum (1/5, 20%) were the less common findings. None of the dogs survived. CONCLUSION: Pneumomediastinum and diffuse or symmetrical interstitial or alveolar lung patterns are the most common radiographic features in dogs with paraquat intoxication. CLINICAL RELEVANCE: In countries where this herbicide is not banned, paraquat intoxication should be considered if dogs with no history of trauma present with pneumomediastinum.


Assuntos
Doenças do Cão/diagnóstico por imagem , Paraquat/envenenamento , Tórax/diagnóstico por imagem , Animais , Cães , Feminino , Doenças Pulmonares Intersticiais/veterinária , Masculino , Enfisema Mediastínico/diagnóstico por imagem , Enfisema Mediastínico/veterinária , Paraquat/urina , Pneumotórax/diagnóstico por imagem , Pneumotórax/veterinária , Radiografia/veterinária , Retropneumoperitônio/diagnóstico por imagem , Retropneumoperitônio/veterinária , Enfisema Subcutâneo/diagnóstico por imagem , Enfisema Subcutâneo/veterinária
17.
Cochrane Database Syst Rev ; 6: CD008084, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34190331

RESUMO

BACKGROUND: This an update of a Cochrane Review. Paraquat is a widely used herbicide, but is also a lethal poison. In some low- and middle-income countries (LMICs) paraquat is commonly available and inexpensive, making poisoning prevention difficult. Most of the people poisoned by paraquat have taken it as a means of self-poisoning. Standard treatment for paraquat poisoning prevents further absorption and reduces the load of paraquat in the blood through haemoperfusion or haemodialysis. The effectiveness of standard treatments is extremely limited. The immune system plays an important role in exacerbating paraquat-induced lung fibrosis. Immunosuppressive treatment using glucocorticoid and cyclophosphamide in combination has been developed and studied as an intervention for paraquat poisoning. OBJECTIVES: To assess the effects of glucocorticoid with cyclophosphamide for moderate to severe oral paraquat poisoning. SEARCH METHODS: The most recent searches were run in September 2020. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Injuries Trials Register), Ovid MEDLINE(R), Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily and Ovid OLDMEDLINE, Embase Classic + Embase (Ovid), ISI WOS (SCI-EXPANDED, SSCI, CPCI-S, and CPSI-SSH), and trials registries. We also searched the following three resources: China National Knowledge Infrastructure database (CNKI ); Wanfang Data (); and VIP () on 12 November 2020. We examined the reference lists of included studies and review papers. SELECTION CRITERIA: We included randomised controlled trials (RCTs). For this update, in accordance with Cochrane Injuries' Group policy (2015), we included only prospectively registered RCTs for trials published after 2010. We included trials which assessed the effects of glucocorticoid with cyclophosphamide delivered in combination. Eligible comparators were standard care (with or without a placebo), or any other therapy in addition to standard care. Outcomes of interest included mortality and infections. DATA COLLECTION AND ANALYSIS: We calculated the mortality risk ratio (RR) and 95% confidence interval (CI). Where possible, we summarised data for all-cause mortality at relevant time periods (from hospital discharge to three months after discharge) in meta-analysis, using a fixed-effect model. We conducted sensitivity analyses based on factors including whether participants were assessed at baseline for plasma paraquat levels. We also reported data on infections within one week after initiation of treatment. MAIN RESULTS: We included four trials with a total of 463 participants. The included studies were conducted in Taiwan (Republic of China), Iran, and Sri Lanka. Most participants were male. The mean age of participants was 28 years. We judged two of the four included studies, including the largest and most recently conducted study (n = 299), to be at low risk of bias for key domains including sequence generation. We assessed one study to be at high risk of selection bias and another at unclear risk, since allocation concealment was either not mentioned in the trial report or explicitly not undertaken. We assessed three of the four studies to be at unclear risk of selective reporting, as no protocols could be identified. An important source of heterogeneity amongst the included studies was the method of assessment of participants' baseline severity using analysis of plasma levels (two studies employed this method, whilst the other two did not). No studies assessed the outcome of mortality at 30 days following ingestion of paraquat. Low-certainty evidence from two studies indicates that glucocorticoids with cyclophosphamide in addition to standard care may slightly reduce the risk of death in hospital compared to standard care alone ((RR 0.82, 95% CI 0.68 to 0.99; participants = 322); results come from sensitivity analysis excluding studies not assessing plasma at baseline). However, we have limited confidence in this finding as heterogeneity was high (I2 = 77%) and studies varied in terms of size and comparators. A single large study provided data showing that there may be little or no effect of treatment at three months post discharge from hospital (RR 0.98, 95% CI 0.85 to 1.13; 1 study, 293 participants; low-certainty evidence); however, analysis of long-term results amongst participants whose injuries arose from self-poisoning must be interpreted with caution. We remain uncertain of the effect of glucocorticoids with cyclophosphamide on infection within one week after initiation of the treatment; this outcome was assessed by two small studies only (31 participants, very low-certainty evidence) that considered leukopenia as a proxy or risk factor for infection. Neither study reported infections in any participants. AUTHORS' CONCLUSIONS: Low-certainly evidence suggests that glucocorticoids with cyclophosphamide in addition to standard care may slightly reduce mortality in hospitalised people with oral paraquat poisoning. However, we have limited confidence in this finding because of substantial heterogeneity and concerns about imprecision. Glucocorticoids with cyclophosphamide in addition to standard care may have little or no effect on mortality at three months after hospital discharge. We are uncertain whether glucocorticoid with cyclophosphamide puts patients at an increased risk of infection due to the limited evidence available for this outcome. Future research should be prospectively registered and CONSORT-compliant. Investigators should attempt to ensure an adequate sample size, screen participants for inclusion rigorously, and seek long-term follow-up of participants. Investigators may wish to research the effects of glucocorticoid in combination with other treatments.


Assuntos
Ciclofosfamida/uso terapêutico , Glucocorticoides/uso terapêutico , Herbicidas/envenenamento , Imunossupressores/uso terapêutico , Paraquat/envenenamento , Fibrose Pulmonar/tratamento farmacológico , Adulto , Viés , Causas de Morte , Quimioterapia Combinada/métodos , Feminino , Humanos , Masculino , Envenenamento/tratamento farmacológico , Envenenamento/mortalidade , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/imunologia , Fibrose Pulmonar/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo
18.
J Environ Sci Health B ; 56(7): 670-674, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34157949

RESUMO

Paraquat is resistant to degradation by conventional treatments, being necessary to use treatments with greater effectiveness, such as advanced oxidative processes. In this work, different advanced oxidative processes were applied (Fenton, electro-Fenton, photoelectro-oxidation and photoelectro-Fenton) employing oxide electrodes to degrade Gramoxone, a commercial herbicide that contains paraquat in its composition. The degradation and formation of by-products were accompanied by high performance liquid chromatography, total organic carbon (TOC) and chemical oxygen demand (COD). The results showed that the photoelectro-Fenton process was the most efficient due to the synergistic effect, reaching 79% degradation of the initial compound and 82% and 71% removal of TOC and COD, respectively. After the application of the electro-Fenton and photoelectro-Fenton oxidation processes, short-chain carboxylic acids such as succinic acid, oxalic acid, acetic acid and formic acid were identified as by-products of the oxidation of Gramoxone. The results were satisfactory and deserve to be highlighted, as a commercial formulation was used, making the scenario more realistic.


Assuntos
Herbicidas , Poluentes Químicos da Água , Eletrodos , Peróxido de Hidrogênio , Oxirredução , Estresse Oxidativo , Paraquat
19.
Int J Mol Sci ; 22(10)2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-34064677

RESUMO

Over the last decade, the knowledge in extracellular vesicles (EVs) biogenesis and modulation has increasingly grown. As their content reflects the physiological state of their donor cells, these "intercellular messengers" progressively became a potential source of biomarker reflecting the host cell state. However, little is known about EVs released from the human brain microvascular endothelial cells (HBMECs). The current study aimed to isolate and characterize EVs from HBMECs and to analyze their EVs proteome modulation after paraquat (PQ) stimulation, a widely used herbicide known for its neurotoxic effect. Size distribution, concentration and presence of well-known EV markers were assessed. Identification and quantification of PQ-exposed EV proteins was conducted by data-independent acquisition mass spectrometry (DIA-MS). Signature pathways of PQ-treated EVs were analyzed by gene ontology terms and pathway enrichment. Results highlighted that EVs exposed to PQ have modulated pathways, namely the ubiquinone metabolism and the transcription HIF-1 targets. These pathways may be potential molecular signatures of the PQ-induced toxicity carried by EVs that are reflecting their cell of origin by transporting with them irreversible functional changes.


Assuntos
Encéfalo/metabolismo , Endotélio Vascular/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Paraquat/efeitos adversos , Proteoma/metabolismo , Ubiquinona/metabolismo , Biomarcadores/análise , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Vesículas Extracelulares , Herbicidas/efeitos adversos , Humanos , Proteoma/análise , Proteoma/efeitos dos fármacos
20.
J Int Med Res ; 49(6): 3000605211026117, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34182818

RESUMO

Diquat is a widely used herbicide that is substituted for paraquat. With paraquat off the market, cases of diquat poisoning have been gradually increasing. The kidney is the most frequently impaired organ in diquat poisoning. Few cases of multiple organ failure caused by diquat have been reported.We herein describe a 30-year-old man who orally ingested about 160 mL of enriched diquat. Despite aggressive treatment, the patient's condition progressed to multiple organ failure and death. The pulmonary lesions in this patient were different from those previously reported. This patient did not die of renal failure but of severe respiratory failure. He exhibited three different stages of pulmonary disease.The lung lesions in this case were unique. We hope that doctors will pay more attention to the lung lesions in patients with diquat poisoning in future and find new treatment methods to save the lives of such patients.


Assuntos
Herbicidas , Insuficiência Respiratória , Adulto , Diquat , Humanos , Masculino , Insuficiência de Múltiplos Órgãos/induzido quimicamente , Paraquat
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