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International Journal of Environmental... Mar 2021The study of the interaction of persistent organic pollutants with biosubstrates helps to unravel the pathways for toxicity, however, few mechanistic data are present in...
The study of the interaction of persistent organic pollutants with biosubstrates helps to unravel the pathways for toxicity, however, few mechanistic data are present in the literature for these systems. We analyzed the binding of paraquat (PQ) and diquat (DQ) herbicides to natural calf thymus DNA and a DNA G-quadruplex by spectrophotometric titrations, ethidium bromide exchange tests, viscometry, and melting experiments. The interaction with bovine serum albumin (BSA) protein was studied spectrofluorimetrically at different temperatures. The retention of the targets on positive, negative, and neutral micellar aggregates and liposomes was analyzed by ultrafiltration experiments. Despite some favorable features, PQ and DQ only externally bind natural DNA and do not interact with DNA oligonucleotides. Both herbicides bind bovine serum albumin (BSA). PQ binds BSA mainly according to an electrostatics-driven process. However, ultrafiltration data also show that some hydrophobic contribution participates in the features of these systems. The practical problems related to unfavorable spectroscopic signals and inner filter effects are also discussed. Overall, both herbicides show a low affinity for nucleic acids and weak penetration into liposomes; in addition, the equilibrium constants values found for BSA system suggest optimal conditions for transport in the body.
Topics: Animals; Cattle; Diquat; Herbicides; Paraquat; Protein Binding; Serum Albumin, Bovine; Spectrum Analysis
PubMed: 33801256
DOI: 10.3390/ijerph18052412 -
Basic & Clinical Pharmacology &... Jun 2021Acute paraquat poisoning resulting from multiple organ failure usually has a high mortality rate. Liver and kidney, as the key oranges of paraquat detoxification and... (Clinical Trial)
Clinical Trial
Acute paraquat poisoning resulting from multiple organ failure usually has a high mortality rate. Liver and kidney, as the key oranges of paraquat detoxification and elimination, their injuries may suppress toxin excretion and enhance the toxicity of paraquat in other organs and worsen the prognosis. Therefore, we intended to explore the prognostic value of liver and kidney function parameters, and further evaluate their correlation with a more stable index urine-to-plasma paraquat (urine paraquat concentrations/plasma paraquat concentrations) instead of considering paraquat concentrations in plasma or urine alone. The study included 33 patients with acute paraquat poisoning admitted to four centres in China from January 2018 to December 2019. Seventeen patients (10 male/7 female) survived, whereas 16 patients (7 male/9 female, 48.48%) died from paraquat poisoning. Alanine aminotransferase (ALT) and the blood urea nitrogen (BUN) represent liver and kidney function parameters, respectively. The ratio of urine-to-plasma paraquat is negatively correlated with ALT (r = -0.94, P = 0 .02) and BUN (r = -0.82, P = 0.03). For receiver operating characteristic curve (ROC) analysis, ALT, BUN and urine-to-plasma paraquat have an AUC over 0.80. The study shows that the functional indexes of liver and kidney, as well as the ratio of urine-to-plasma paraquat, could be considered for evaluating the extent of organ injury and excretion rate of paraquat.
Topics: Adolescent; Adult; Aged; Alanine Transaminase; Blood Urea Nitrogen; China; Female; Humans; Kidney; Liver; Male; Middle Aged; Paraquat; Retrospective Studies
PubMed: 33411948
DOI: 10.1111/bcpt.13555 -
Toxicological Sciences : An Official... Jul 2020Paraquat (PQ) is an herbicide used in many countries, including the United States. It is also implicated as a risk factor for sporadic Parkinson's disease, especially in...
Paraquat (PQ) is an herbicide used in many countries, including the United States. It is also implicated as a risk factor for sporadic Parkinson's disease, especially in those living in agricultural areas and drinking well water. Studies linking PQ to sporadic Parkinson's disease are not consistent however and there appears to be interindividual differential susceptibility. One likely reason is genetically based differential susceptibility to paraquat neurotoxicity in subpopulations. To address this issue, we tested the effects of paraquat in a genetic reference population of mice (the BXD recombinant inbred strain family). In our earlier work, we showed that in genetically susceptible mice, paraquat increases iron in the ventral midbrain, the area containing the substantia nigra. Our hypothesis is that genetic variability contributes to diverse PQ-related susceptibility and iron concentration. To test this hypothesis, we treated male mice from 28 to 39 BXD strains plus the parental strains with 1 of 3 doses of paraquat, 1, 5, and 10 mg/kg 3 times on a weekly basis. At the end of the treatment period, we analyzed the ventral midbrain for concentrations of iron, copper, and zinc, also we measured the concentration of paraquat in cerebellum, and proinflammatory cytokines in serum and cerebellum. The effect on paraquat-treated mice with 5 mg/kg and principal component analysis of iron showed suggestive quantitative trait loci on chromosome 5. Overall, our results suggest that gene Prkag2 and related networks may serve as potential targets against paraquat toxicity and demonstrate the utility of genetically diverse mouse models for the study of complex human toxicity.
Topics: Animals; Brain; Herbicides; Iron; Male; Mesencephalon; Mice; Mice, Inbred C57BL; Paraquat; Parkinson Disease; Substantia Nigra; Systems Biology
PubMed: 32294219
DOI: 10.1093/toxsci/kfaa050 -
Yonsei Medical Journal Jul 2017In Korea, registration of paraquat-containing herbicides was canceled in November 2011, and sales thereof were completely banned in November 2012. We evaluated the...
PURPOSE
In Korea, registration of paraquat-containing herbicides was canceled in November 2011, and sales thereof were completely banned in November 2012. We evaluated the effect of the paraquat ban on the epidemiology and mortality of herbicide-induced poisoning.
MATERIALS AND METHODS
This retrospective study analyzed patients treated for herbicide poisoning at 17 emergency departments in South Korea between January 2010 and December 2014. The overall and paraquat mortality rates were compared pre- and post-ban. Factors associated with herbicide mortality were evaluated using logistic analysis. To determine if there were any changes in the mortality rates before and after the paraquat sales ban and the time point of any such significant changes in mortality, R software, version 3.0.3 (package, bcp) was used to perform a Bayesian change point analysis.
RESULTS
We enrolled 2257 patients treated for herbicide poisoning (paraquat=46.8%). The overall and paraquat poisoning mortality rates were 40.6% and 73.0%, respectively. The decreased paraquat poisoning mortality rate (before, 75% vs. after, 67%, p=0.014) might be associated with increased intentionality. The multivariable logistic analysis revealed the paraquat ban as an independent predictor that decreased herbicide poisoning mortality (p=0.035). There were two major change points in herbicide mortality rates, approximately 3 months after the initial paraquat ban and 1 year after complete sales ban.
CONCLUSION
This study suggests that the paraquat ban decreased intentional herbicide ingestion and contributed to lowering herbicide poisoning-associated mortality. The change point analysis suggests a certain timeframe was required for the manifestation of regulatory measures outcomes.
Topics: Bayes Theorem; Demography; Female; Geography; Herbicides; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Paraquat; Poisoning; Republic of Korea
PubMed: 28541002
DOI: 10.3349/ymj.2017.58.4.859 -
Ecotoxicology and Environmental Safety Jan 2023Although programmed cell death (PCD) has been reported in phytoplankton, knowledge of the characterization of the PCD pathway and cascade process in different...
Although programmed cell death (PCD) has been reported in phytoplankton, knowledge of the characterization of the PCD pathway and cascade process in different phytoplankton species is still limited. In this study, PCD progression in cyanobacterium Microcystis aeruginosa and green algae Chlorella luteoviridis by paraquat-induced oxidative stress was monitored. The results showed that paraquat-induced PCD in the two species belonged to the caspase-dependent pathway. Dose- and time-dependent PCD characteristics in the two strains under paraquat included the increase in caspase-like activity, DNA fragmentation, and chromatin condensation. However, the signaling pathway and cascade events of PCD in M. aeruginosa and C. luteoviridis differed. In M. aeruginosa, the free Ca concentration was rapidly increased at 8 h, followed by a significant elevation of the reactive oxygen species (ROS) level at 24 h, and eventual cell death. In C. luteoviridis, the mitochondrial apoptosis pathway, revealed by the depolarization of the mitochondrial membrane potential at 1 h and increase in the ROS level and caspase-like activity at 8 h, might contribute to cell death. In addition, the dynamics of ROS levels and metacaspase activity were synchronized, suggesting that paraquat-triggered PCD was ROS-mediated in both M. aeruginosa and C. luteoviridis. These results provide insights into PCD patterns in prokaryotic cyanobacteria and eukaryotic green algae under similar stress.
Topics: Microcystis; Paraquat; Reactive Oxygen Species; Chlorella; Apoptosis; Caspases; Cyanobacteria
PubMed: 36516625
DOI: 10.1016/j.ecoenv.2022.114429 -
International Journal of Environmental... Jun 2018This study aimed to assess paraquat concentrations in the urine of women at 28 weeks of pregnancy, delivery and 2 months postpartum and in the meconium of neonates. In...
This study aimed to assess paraquat concentrations in the urine of women at 28 weeks of pregnancy, delivery and 2 months postpartum and in the meconium of neonates. In all, 79 pregnant women were recruited from three hospitals located in agricultural areas in Thailand. The subjects were interviewed about personal characteristics, agricultural activities and pesticide use patterns. Paraquat was analyzed in urine and meconium using high performance liquid chromatography equipped with a fluorescence detector. The geometric mean (GSD) of urinary paraquat concentrations at 28 weeks of pregnancy, delivery and 2 months postpartum were 2.04 (4.22), 2.06 (5.04) and 2.42 (5.33) ng/mL, respectively. The urinary paraquat concentrations at 28 weeks of pregnancy, delivery and 2 months postpartum between agriculturist and non-agriculturist were not significantly different ( = 0.632, = 0.915, = 0.57 respectively). The geometric mean (GSD) of paraquat concentration in the meconium was 33.31 (4.59) ng/g. The factors predicting paraquat exposures among pregnant women and neonates included working outside, living near farmland, having family members who work on a farm, drinking well water and using herbicides or paraquat.
Topics: Adult; Agriculture; Environmental Exposure; Female; Humans; Infant, Newborn; Maternal Exposure; Meconium; Paraquat; Pesticides; Postpartum Period; Pregnancy; Pregnant Women; Thailand; Young Adult
PubMed: 29865285
DOI: 10.3390/ijerph15061163 -
Sensors (Basel, Switzerland) Jan 2023Paraquat (PQ) and diquat (DQ), some of the most widely used herbicides in the world, both present a high mortality index after intentional exposure. In this paper, a...
Paraquat (PQ) and diquat (DQ), some of the most widely used herbicides in the world, both present a high mortality index after intentional exposure. In this paper, a fluorescence sensing method for PQ and DQ, based on host-guest molecular recognition, is proposed. Calix[6]arene derivatives containing anthracene or naphthalene as pendant fluorophore at their lower rim recognize DQ and PQ in hydroalcoholic solution with a broad linear response range at the μg L level concentration. The linear response ranges were found from 1.0 to 18 μg L with the detection limit of 31 ng L for paraquat, and from 1.0 to 44 μg L with the detection limit of 0.16 μg L for diquat. The recognition process is detected by following the decrease in the fluorescence emission consequent to complexation. The proposed quenching method has been applied to the determination of paraquat in drinking water samples.
Topics: Diquat; Paraquat; Fluorescence; Herbicides
PubMed: 36772161
DOI: 10.3390/s23031120 -
Journal of Chromatography. B,... Jan 2023Benzalkyldimethylammonium (or benzalkonium; BACs), alkyltrimethylammonium (ATMACs), and dialkyldimethylammonium compounds (DDACs) have been widely used for over six...
Benzalkyldimethylammonium (or benzalkonium; BACs), alkyltrimethylammonium (ATMACs), and dialkyldimethylammonium compounds (DDACs) have been widely used for over six decades as disinfectants, especially during the COVID-19 pandemic. Here we describe methods for the determination of 7 BACs, 6 ATMACs, 6 DDACs, 8 BAC metabolites, and the structurally similar quaternary ammonium compound (QAC) herbicides diquat, paraquat, and difenzoquat in human serum and urine using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The methods were optimized using isotopically labelled internal standards and solid-phase extraction with weak cation-exchange cartridges. We separated diquat and paraquat chromatographically using a mixed-mode LC column, and BACs, ATMACs, DDACs, difenzoquat, and BAC metabolites using reversed-phase (C8 and C18) LC columns. Method limits of detection (MLODs) and quantification (MLOQs) were 0.002-0.42 and 0.006-1.40 ng/mL, respectively. Recoveries of all analytes fortified at 1, 5, and 20 ng/mL concentrations in serum and urine matrices were 61-129%, with standard deviations of 0-20%. Repeated analysis of similarly fortified serum and urine samples yielded intra-day and inter-day variations of 0.22-17.4% and 0.35-17.3%, respectively. Matrix effects for analytes spiked into serum and urine matrices ranged from -27% to 15.4%. Analysis of real urine and serum samples revealed the presence of several QACs in human serum. Although no parent BACs were found in urine, we detected, for the first time, several ω-hydroxy and ω-carboxylic acid metabolites of BACs at average concentrations in the range of 0.05-0.35 ng/mL. The developed method is suitable for application in large-scale biomonitoring of human exposure to QACs and their metabolites in human serum and urine.
Topics: Humans; Paraquat; Chromatography, Liquid; Diquat; Benzalkonium Compounds; Quaternary Ammonium Compounds; Tandem Mass Spectrometry; Pandemics; COVID-19
PubMed: 36495685
DOI: 10.1016/j.jchromb.2022.123562 -
The Cochrane Database of Systematic... Jun 2010Paraquat is an effective and widely used herbicide but is also a lethal poison. In many developing countries paraquat is widely available and inexpensive, making... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Paraquat is an effective and widely used herbicide but is also a lethal poison. In many developing countries paraquat is widely available and inexpensive, making poisoning prevention difficult. However most of the people who become poisoned from paraquat have taken it as a means of suicide.Standard treatment for paraquat poisoning both 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 is being developed and studied.
OBJECTIVES
To assess the effects of glucocorticoid with cyclophosphamide on mortality in patients with paraquat-induced lung fibrosis.
SEARCH STRATEGY
To identify randomised controlled trials on this topic, we searched the Cochrane Injuries Group's Specialised Register (searched 15 Sept 2009), CENTRAL (The Cochrane Library 2009, Issue 3), MEDLINE (Ovid SP) (1950 September Week 1 2009), EMBASE (Ovid SP) (1980 to 2009 Week 37), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) (1970 to Sept 2009), ISI Web of Science: Conference Proceedings Citation Index - Science (CPCI-S) (1990 to Sept 2009), Chinese bio-medical literature & retrieval system (CBM) (1978 to Sept 2009), Chinese medical current contents (CMCC) (1995 to Sept 2009), and Chinese medical academic conference (CMAC) (1994-Sept 2009). The searches were completed in September 2009.
SELECTION CRITERIA
Randomised controlled trials (RCTs) were included in this review. All patients were to receive standard care, plus the intervention or control. The intervention was glucocorticoid with cyclophosphamide in combination versus a control of a placebo, standard care alone, or any other therapy in addition to standard care.
DATA COLLECTION AND ANALYSIS
The mortality risk ratio (RR) and 95% confidence interval (CI) was calculated for each study on an intention-to-treat basis. Data for all-cause mortality at final follow-up were summarised in a meta-analysis using a fixed-effects model.
MAIN RESULTS
This systematic review includes three trials with a combined total of 164 participants who had moderate to severe paraquat poisoning. Patients who received glucocorticoid with cyclophosphamide in addition to standard care had a lower risk of death at final follow-up than those receiving standard care only (RR 0.72 (95% CI 0.59 to 0.89)).
AUTHORS' CONCLUSIONS
Based on the findings of three small RCTs of moderate to severely poisoned patients, glucocorticoid with cyclophosphamide in addition to standard care may be a beneficial treatment for patients with paraquat-induced lung fibrosis. To enable further study of the effects of glucocorticoid with cyclophosphamide for patients with moderate to severe paraquat poisoning, hospitals may provide this treatment as part of an RCT with allocation concealment.
Topics: Cyclophosphamide; Drug Therapy, Combination; Glucocorticoids; Humans; Paraquat; Pulmonary Fibrosis; Randomized Controlled Trials as Topic
PubMed: 20556790
DOI: 10.1002/14651858.CD008084.pub2 -
Microglia-derived exosomal circZNRF1 alleviates paraquat-induced neuronal cell damage via miR-17-5p.Ecotoxicology and Environmental Safety Sep 2023Paraquat (PQ) is an environmental poison that causes clinical symptoms similar to those of Parkinson's disease (PD) in vitro and in rodents. It can lead to the...
Paraquat (PQ) is an environmental poison that causes clinical symptoms similar to those of Parkinson's disease (PD) in vitro and in rodents. It can lead to the activation of microglia and apoptosis of dopaminergic neurons. However, the exact role and mechanism of microglial activation in PQ-induced neuronal degeneration remain unknown. Here, we isolated the microglia-derived exosomes exposed with 0 and 40 μM PQ, which were subsequently co-incubated with PQ-exposed neuronal cells to simulate intercellular communication. First, we found that exosomes released from microglia caused a change in neuronal cell vitality and reversed PQ-induced neuronal apoptosis. RNA sequencing data showed that these activated microglia-derived exosomes carried large amounts of circZNRF1. Moreover, a bioinformatics method was used to study the underlying mechanism of circZNRF1 in regulating PD, and miR-17-5p was predicted to be its target. Second, an increased Bcl2/Bax ratio could play an anti-apoptotic role. Bcl2 was predicted to be a downstream target of miR-17-5p. Our results showed that circZNRF1 plays an anti-apoptotic role by absorbing miR-17-5p and regulating the binding of Bcl2 after exosomes are internalized by dopaminergic neurons. In conclusion, we demonstrated a new intercellular communication mechanism between microglia and neurons, in which circZNRF1 plays a key role in protecting against PQ-induced neuronal apoptosis through miR-17-5p to regulate the biological process of PD. These findings may offer a novel approach to preventing and treating PD.
Topics: Microglia; Paraquat; Dopaminergic Neurons; Proto-Oncogene Proteins c-bcl-2; MicroRNAs
PubMed: 37591128
DOI: 10.1016/j.ecoenv.2023.115356