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Journal of the Chinese Medical... Oct 2009Paraquat is a substance that is highly poisonous to humans. Oral ingestion is the most common pathway of poisoning. Intravenous paraquat poisoning is rare and is... (Review)
Review
Paraquat is a substance that is highly poisonous to humans. Oral ingestion is the most common pathway of poisoning. Intravenous paraquat poisoning is rare and is strongly associated with attempted suicide. The clinical presentations of such a scenario would appear to be quite different from those of oral ingestion. Herein, we present a case of an intravenous drug abuser who injected paraquat in an effort to commit suicide. He received hemoperfusion and intravenous cyclophosphamide treatment and parenteral pulse therapy with methylprednisolone. Nevertheless, he suffered from dyspnea at around 48 hours post-exposure. His condition improved transiently, but he eventually died from severe hypoxia. The findings from our case and those of previously reported cases indicate the grave prognosis and lack of effective management of intravenous paraquat poisoning.
Topics: Adult; Herbicides; Humans; Injections, Intravenous; Male; Paraquat; Suicide
PubMed: 19837651
DOI: 10.1016/S1726-4901(09)70426-5 -
Environmental Science and Pollution... Feb 2023A small proportion of the thousands of pesticides on the market today are associated with a disproportionately high incidence of severe acute pesticide poisoning and... (Review)
Review
A small proportion of the thousands of pesticides on the market today are associated with a disproportionately high incidence of severe acute pesticide poisoning and suicide. Paraquat stands out as one of the most lethal pesticides in common use, frequently involved in fatal incidents due to suicides or accidental exposure. Even though paraquat has been banned in over 67 countries, it is still widely used in many others, particularly in Asia and Latin America. Based on a literature review and consultations, this paper identifies options for replacing paraquat and distils practical lessons from numerous successes around the world. Our aim is to support regulators, policymakers, agronomists and the supply chain sector with practical information related to phasing out paraquat. Production data consistently failed to show any negative effects of banning paraquat on agricultural productivity. A wide range of alternative approaches to weed management and crop defoliation are available, many of which do not rely on herbicides. Over 1.25 million farmers in low- and middle-income countries (LMICs) successfully produce a range of crops for private voluntary standards (PVS) in food and fiber supply chains which prohibit paraquat use. We conclude from the findings of this study that eliminating paraquat will save lives without reducing agricultural productivity. Less hazardous and more sustainable alternatives exist. To enhance successful adoption and uptake of these methods on a wide scale, farmers require training and support within an enabling policy environment.
Topics: Humans; Herbicides; Paraquat; Suicide; Agriculture; Pesticides
PubMed: 36622585
DOI: 10.1007/s11356-022-24951-0 -
European Review For Medical and... Apr 2016To identify the mechanisms involved in paraquat (PQ)-induced pulmonary injury. (Review)
Review
OBJECTIVE
To identify the mechanisms involved in paraquat (PQ)-induced pulmonary injury.
MATERIALS AND METHODS
The mechanism of PQ-induced pulmonary injury was elucidated through both literature review and experimentation.
RESULTS
As an effective herbicide, PQ has been widely used in farmland and pasture, it has a characteristic potent weeding effect. However, PQ is highly toxic to humans and there is no specific medical treatment available. Paraquat has been used frequently by suicidal people to end their life; its mortality is > 90% in oral ingestion cases. It has recently been recognized that PQ causes respiratory failure and even death through multiple organ failures, particularly through pulmonary fibrosis. However, the mechanisms of PQ-induced pulmonary injury had not been clarified.
CONCLUSIONS
In this review, we systematically elucidated the mechanism of PQ-induced pulmonary injury, and concluded that PQ causes pulmonary injury through oxidative, alveolar, mitochondrial, lipid and metabolic enzyme damage, all of which can lead to death due to pulmonary fibrosis. With this in mind, we propose recommendations for the treatment of PQ-induced pulmonary injury and provide theoretical bases for subsequent treatment strategies.
Topics: Herbicides; Humans; Lung Injury; Mitochondria; Paraquat; Pulmonary Fibrosis
PubMed: 27160134
DOI: No ID Found -
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 -
Journal of Biochemical and Molecular... May 2014Paraquat is an herbicide used extensively in agriculture and has also been proposed to be a risk factor for Parkinson's disease. To date, experimental, clinical, and... (Review)
Review
Paraquat is an herbicide used extensively in agriculture and has also been proposed to be a risk factor for Parkinson's disease. To date, experimental, clinical, and epidemiological data on paraquat neurotoxicity have been equivocal. In this short review, we discuss some technical and biological mechanisms that contribute to inconsistencies regarding paraquat neurotoxicity. We hypothesize that individual genetic variations in susceptibility generate major differences in neurotoxic risk and functional outcome. Identifying these heritable sources of variation in host susceptibility, and their role in complex gene-environment interactions, is crucial to identify risk biomarkers and to devise better prevention and treatment for those exposed to paraquat and other potential neurotoxicants.
Topics: Environmental Pollutants; Gene-Environment Interaction; Genetic Predisposition to Disease; Herbicides; Humans; Neurotoxicity Syndromes; Paraquat
PubMed: 24599642
DOI: 10.1002/jbt.21552 -
Toxicology and Applied Pharmacology Apr 2021By extending our Paraquat (PQ) work to include primates we have implemented a modelling and simulation strategy that has enabled PQ pharmacokinetic data to be integrated...
By extending our Paraquat (PQ) work to include primates we have implemented a modelling and simulation strategy that has enabled PQ pharmacokinetic data to be integrated into a single physiologically based pharmacokinetic (PBPK) model that enables more confident extrapolation to humans. Because available data suggested there might be differences in PQ kinetics between primates and non-primates, a radiolabelled study was conducted to characterize pharmacokinetics and excretion in Cynomolgus monkeys. Following single intravenous doses of 0.01 or 0.1 mg paraquat dichloride/kg bw, plasma PQ concentration-time profiles were dose-proportional. Excretion up to 48 h (predominantly urinary) was 82.9%, with ca. 10% remaining unexcreted. In vitro blood binding was similar across Cynomolgus monkeys, humans and rat. Our PBPK model for the rat, mouse and dog, employing a single set of PQ-specific parameters, was scaled to Cynomolgus monkeys and well represented the measured plasma concentration-time profiles over 14 days. Addition of a cartilage compartment to the model better captured the percent remaining in the monkeys at 48 h, whilst having negligible effect on model predictions for the other species. The PBPK model performed well for all four species, demonstrating there is little difference in PQ kinetics between non-primates and primates enabling a more confident extrapolation to humans. Scaling of the PBPK model to humans, with addition of a human-specific dermal submodel based on in vitro human dermal absorption data, provides a valuable tool that could be employed in defining internal dosimetry to complement human health risk assessments.
Topics: Animals; Computer Simulation; Herbicides; Humans; Infusions, Intravenous; Intestinal Elimination; Macaca fascicularis; Models, Biological; Paraquat; Rats; Renal Elimination; Risk Assessment; Skin Absorption; Species Specificity; Tissue Distribution; Toxicokinetics
PubMed: 33631232
DOI: 10.1016/j.taap.2021.115463 -
The American Journal of Pathology May 2023Abnormal aggregation of α-synuclein (αS) is thought to initiate neuronal dysfunction and death in Parkinson disease (PD). In addition to higher-molecular-weight,...
Abnormal aggregation of α-synuclein (αS) is thought to initiate neuronal dysfunction and death in Parkinson disease (PD). In addition to higher-molecular-weight, oligomeric, and polymeric forms of αS associated with neurotoxicity and disease, recent findings indicate the occurrence of physiological tetrameric assemblies in healthy neurons in culture and in brain. Herein, the PD-associated neurotoxin paraquat reduced physiological tetramers and led to calpain-truncated monomers and an approximately 70-kDa apparent oligomer different in size from physiological αS multimers. These truncated and oligomeric forms could also be generated by calpain cleavage of pure, recombinant human αS in vitro. Moreover, they were detected in the brains of tetramer-abrogating, E46K-amplified (3K) mice that model PD. These results indicate that paraquat triggers membrane damage and aberrant calpain activity that can induce a pathologic shift of tetramers toward an excess of full-length and truncated monomers, the accumulation of αS oligomers, and insoluble cytoplasmic αS puncta. The findings suggest that an environmental precipitant of PD can alter αS tetramer/monomer equilibrium, as already shown for several genetically caused forms of PD.
Topics: Mice; Humans; Animals; alpha-Synuclein; Parkinson Disease; Calpain; Paraquat
PubMed: 36773784
DOI: 10.1016/j.ajpath.2023.01.010 -
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 -
Scientific Reports Mar 2022In this study, toxicity caused by 50, 100 and 200 mg/kg b.w doses of Paraquat herbicide in Swiss albino mice was investigated. Body weight, liver and kidney organ...
In this study, toxicity caused by 50, 100 and 200 mg/kg b.w doses of Paraquat herbicide in Swiss albino mice was investigated. Body weight, liver and kidney organ weights, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzyme activities, blood urea nitrogen (BUN) and creatinine levels, malondialdehyde (MDA) and glutathione (GSH) levels in liver and kidney, micronucleus (MN) formation in buccal mucosal epithelium, erythrocyte and leukocyte cells and chromosomal aberrations (CAs) in bone marrow cells, viability of liver and kidney cells were investigated. Four groups were randomly formed from male Swiss albino mice (one control and three treatment groups). The control group mice were provided tap water and the mice in the treatment groups were treated orally with three different doses of Paraquat (50, 100 and 200 mg/kg b.w) in the drinking water for 28 days. At the end of the application, all mice were sacrificed and routine preparation procedures were carried out to examine physiological, biochemical, oxidative stress and genetic parameters. Paraquat administration decreased physiological parameters (body, liver and kidney organ weights), and increased biochemical parameters (AST, ALT, BUN, creatinine and MDA). GSH levels were decreased depending on the dose. Kidney and liver damage were confirmed by the trypan blue test. Paraquat administration promoted MN formation in buccal mucosal epithelium, erythrocyte and leukocyte cells depending on the dose. The highest MN frequency was observed in leukocyte cells exposed to a dose of 200 mg/kg b.w of Paraquat. Deteriorations in DNA integrity as a result of MN formations were supported by the comet assay. In addition, Paraquat promoted CAs such as break, fragment, acentric, dicentric, gap and ring in bone marrow cells. Break damage was the most common among these damages. These observed genotoxic effects occured as a result of the interaction of DNA and DNA-related proteins with Paraquat. Molecular docking studies showed that Paraquat binds to histone H4 protein with high affinity and has a high intercalation potential. As a result, Paraquat herbicide caused a significant toxicity by changing physiological, biochemical, oxidative stress and genetic parameters of Swiss albino mice depending on the application dose.
Topics: Animals; Creatinine; DNA; Glutathione; Herbicides; Male; Mice; Molecular Docking Simulation; Paraquat
PubMed: 35314741
DOI: 10.1038/s41598-022-08961-z -
Journal of Korean Medical Science Nov 2014Paraquat (PQ) has known negative human health effects, but continues to be commonly used worldwide as a herbicide. Our clinical data shows that the main prognostic... (Review)
Review
Paraquat (PQ) has known negative human health effects, but continues to be commonly used worldwide as a herbicide. Our clinical data shows that the main prognostic factor is the time required to achieve a negative urine dithionite test. Patient survival is a 100% when the area affected by ground glass opacity is <20% of the total lung volume on high-resolution computed tomography imaging 7 days post-PQ ingestion. The incidence of acute kidney injury is approximately 50%. The average serum creatinine level reaches its peak around 5 days post-ingestion, and usually normalizes within 3 weeks. We obtain two connecting lines from the highest PQ level for the survivors and the lowest PQ level among the non-survivors at a given time. Patients with a PQ level between these two lines are considered treatable. The following treatment modalities are recommended to preserve kidney function: 1) extracorporeal elimination, 2) intravenous antioxidant administration, 3) diuresis with a fluid, and 4) cytotoxic drugs. In conclusion, this review provides a general overview on the diagnostic procedure and treatment modality of acute PQ intoxication, while focusing on our clinical experience.
Topics: Acute Kidney Injury; Antioxidants; Creatinine; Hemoperfusion; Herbicides; Humans; Iron Chelating Agents; Lung Diseases; Paraquat; Tomography, X-Ray Computed
PubMed: 25408572
DOI: 10.3346/jkms.2014.29.11.1441