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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 -
Environmental and Molecular Mutagenesis Jan 2022We previously showed that farmers in Bolivia are exposed to many pesticides, some at elevated levels, and that this was associated with increased risk of genetic damage....
We previously showed that farmers in Bolivia are exposed to many pesticides, some at elevated levels, and that this was associated with increased risk of genetic damage. To improve the understanding of possible mixture effects, the cytotoxicity and genotoxicity of pesticides were studied in vitro using human liver HepG2 cells. The studied pesticides were 2,4-D, chlorpyrifos, cypermethrin, glyphosate, methamidophos, paraquat, profenofos, and tebuconazole. Three mixtures (U1, U2, and U3) were based on profiles of urinary pesticide metabolites and one mixture on the most frequently used pesticides (S1). The results showed that paraquat and methamidophos were the most cytotoxic pesticides (EC ≤0.3 mM). Paraquat, chlorpyrifos, tebuconazole, and the U1, U2, and U3 mixtures, which contained a large proportion of either chlorpyrifos or tebuconazole, significantly increased intracellular ROS levels. Most pesticides activated DNA damage signaling through proteins Chk1 and H2AX. Strongest responses were elicited by paraquat, profenofos, chlorpyrifos, cypermethrin, and the S1 mixture, which contained 25% paraquat. Comet assay revealed significant increases of DNA damage in response to paraquat, cypermethrin, and U2 and S1 mixtures, which contained high levels of cypermethrin and paraquat, respectively. In summary, we showed that the tested pesticides, alone or in mixtures, in general induced oxidative stress and that most pesticides, and especially paraquat and cypermethrin, were genotoxic in HepG2 cells. We could also show that mixtures dominated by these two pesticides displayed a marked genotoxic potency, which agreed with our previous population studies.
Topics: Bolivia; Chlorpyrifos; DNA Damage; Farmers; Humans; Paraquat; Pesticides
PubMed: 34881454
DOI: 10.1002/em.22468 -
Journal of Hazardous Materials Aug 2021The immediate and the late effects of inhaled Paraquat (PQ) on systemic and lung inflammation and oxidative stress were investigated. Rats were exposed to saline...
The immediate and the late effects of inhaled Paraquat (PQ) on systemic and lung inflammation and oxidative stress were investigated. Rats were exposed to saline (control group) and two doses of inhaled PQ (27 and 54 mg/m) and studied variables were measured: 1) one day after the end of PQ exposure as "immediate condition", 2) 16 days after the end of PQ exposure as "late condition". Total and differential white blood cells (WBC) counts, lipid peroxidation and nitrite were increased but thiol, superoxide dismutase and catalase in the blood and BALF as well as methacholine EC50 was reduced in both conditions in the animals exposed to PQ compared to control groups (p < 0. 05 to p < 0.001). Most studied parameters in the immediate condition were significantly higher than the late condition (p < 0.05 to p < 0.001). Systemic and lung inflammation and oxidative stress due to inhaled PQ in both the immediate and the late conditions were shown. Although most measured parameters in the immediate condition were higher, all variables were significantly different with the control group even in late condition, indicating a long-term effect of inhaled PQ toxicity, which may help in a more effective treatment of PQ poising in the future.
Topics: Animals; Lipid Peroxidation; Lung; Oxidative Stress; Paraquat; Rats; Rats, Sprague-Dawley
PubMed: 33743382
DOI: 10.1016/j.jhazmat.2021.125633 -
Environmental Pollution (Barking, Essex... Dec 2021Paraquat (PQ) is a toxic, organic herbicide for which there is no specific antidote. Although banned in some countries, it is still used as an irreplaceable weed killer... (Review)
Review
Paraquat (PQ) is a toxic, organic herbicide for which there is no specific antidote. Although banned in some countries, it is still used as an irreplaceable weed killer in others. The lack of understanding of the precise mechanism of its toxicity has hindered the development of treatments for PQ exposure. While toxicity is thought to be related to PQ-induced oxidative stress, antioxidants are limited in their ability to ameliorate the untoward biological responses to this agent. Summarized in this review are data on the absorption, distribution, metabolism, excretion, and toxicity (ADME/T) of PQ, focusing on the essential roles of individual transporters and enzymes in these processes. Based on these findings, strategies are proposed to design and test specific and effective antidotes for the clinical management of PQ poisoning.
Topics: Antidotes; Antioxidants; Herbicides; Oxidative Stress; Paraquat
PubMed: 34536650
DOI: 10.1016/j.envpol.2021.118137 -
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 -
Pest Management Science Sep 2014The aim of this brief review is to draw information from studies of the mechanism of evolved resistance in weeds, together with information from laboratory studies of... (Review)
Review
The aim of this brief review is to draw information from studies of the mechanism of evolved resistance in weeds, together with information from laboratory studies of paraquat tolerance in model plants. Plants having mutations that limit paraquat uptake into cytoplasm, that confer various stress tolerances or that have transgenes that co-express two or more of the chloroplast Halliwell-Asada cycle enzymes can all exhibit enhanced tolerance to paraquat. However, none of these mechanisms correspond to the high-level resistances that have evolved naturally in weeds. Most, but not all, of the evidence from studies of paraquat-resistant biotypes of weeds can reasonably be reconciled with the proposal of a single major gene mechanism that sequesters paraquat away from chloroplasts and into the vacuole. However, the molecular details of this putative mechanism remain ill-defined.
Topics: Chloroplasts; Herbicide Resistance; Herbicides; Paraquat; Plant Weeds; Plants
PubMed: 24307186
DOI: 10.1002/ps.3699 -
Analytical and Bioanalytical Chemistry Mar 2022Paraquat is a quaternary ammonium herbicide with an excellent herbicidal effect but is highly toxic to human and animals. Although prohibited by many countries,...
Paraquat is a quaternary ammonium herbicide with an excellent herbicidal effect but is highly toxic to human and animals. Although prohibited by many countries, paraquat intoxication occurred occasionally and caused severe consequences. Rapid and accurate determination of paraquat concentration in intoxication samples is urgently needed in the clinic to promptly evaluate the prognosis of poisoning patients. Here we report an internal standard surface-enhanced Raman spectroscopy (IS-SERS) quantification method on paraquat in mouse plasma and lung tissues for the first time. One measurement per sample was fulfilled within 10 s via this IS-SERS method. Paraquat had good linearity in the range of 1 ~ 500 μg/L (plasma sample) and 1 ~ 100 μg/g (lung sample), with the LOD and LOQ of 0.5 μg/L and 0.1 μg/g (plasma sample), and 5 μg/L and 1 μg/g (lung sample), respectively. This IS-SERS method was validated according to the international guidelines and applied to a quantitative determination and the toxicokinetics on paraquat in mouse plasma and lung tissues. The results indicated that paraquat had a fast absorption rate and a slow elimination rate in mouse plasma and lung tissues. Paraquat was prone to accumulate in target organs after entering the blood. It also proved its good practical applicability in one clinical intoxication sample. Meanwhile, we unveiled an underestimation of free paraquat amount towards common biological sample pretreatment, a certain amount of paraquat bound to components with molecular weight less than 30 kDa in the plasma; we hope it could provide some interesting information for possible clinic treatment.
Topics: Animals; Herbicides; Humans; Lung; Mice; Paraquat; Spectrum Analysis, Raman; Toxicokinetics
PubMed: 35061062
DOI: 10.1007/s00216-022-03875-1 -
Parkinsonism & Related Disorders Feb 2024The four features of Parkinson's disease (PD), which also manifests other non-motor symptoms, are bradykinesia, tremor, postural instability, and stiffness. The... (Review)
Review
The four features of Parkinson's disease (PD), which also manifests other non-motor symptoms, are bradykinesia, tremor, postural instability, and stiffness. The pathogenic causes of Parkinsonism include Lewy bodies, intracellular protein clumps of αsynuclein, and the degeneration of dopaminergic neurons in the substantia nigra's pars compacta region. The pathophysiology of PD is still poorly understood due to the complexity of the illness. The apoptotic cell death of neurons in PD, however, has been linked to a variety of intracellular mechanisms, according to a wide spectrum of study. The endoplasmic reticulum's stress, decreased levels of neurotrophic factors, oxidative stress, mitochondrial dysfunction, catabolic alterations in dopamine, and decreased activity of tyrosine hydroxylase are some of these causes. The herbicide paraquat has been used in laboratory studies to create a variety of PD pathological features in numerous in-vitro and in-vivo animals. Due to the unique neurotoxicity that paraquat causes, understanding of the pathophysiology of PD has changed. Parkinson's disease (PD) is more likely to develop among people exposed to paraquat over an extended period of time, according to epidemiological studies. Thanks to this paradigm, the hunt for new therapy targets for PD has expanded. In both in-vitro and in-vivo models, the purpose of this study is to summarise the relationship between paraquat exposure and the onset of Parkinson's disease (PD).
Topics: Humans; Animals; Paraquat; Herbicides; Parkinson Disease; Parkinsonian Disorders; Dopaminergic Neurons
PubMed: 38008593
DOI: 10.1016/j.parkreldis.2023.105932 -
American Journal of Physiology. Lung... Oct 2023Inhalation of noxious gasses induces oxidative stress in airway epithelial cells (AECs), which may lead to cellular senescence and contribute to the development of...
Inhalation of noxious gasses induces oxidative stress in airway epithelial cells (AECs), which may lead to cellular senescence and contribute to the development of chronic obstructive pulmonary disease (COPD). FAM13A, a well-known COPD susceptibility gene, is highly expressed in airway epithelium. We studied whether its expression is associated with aging and cellular senescence and affects airway epithelial responses to paraquat, a cellular senescence inducer. The association between age and expression was investigated in two datasets of human lung tissue and bronchial brushings from current/ex-smokers with/without COPD. Protein levels of FAM13A and cellular senescence marker p21 were investigated using immunohistochemistry in lung tissue from patients with COPD. In vitro, and expression was assessed using qPCR in air-liquid-interface (ALI)-differentiated AECs in absence/presence of paraquat. In addition, FAM13A was overexpressed in human bronchial epithelial 16HBE cells and the effect on expression (qPCR) and mitochondrial reactive oxygen species (ROS) production (MitoSOX staining) was assessed. Lower expression was significantly associated with increasing age in lung tissue and bronchial epithelium. In airway epithelium of patients with COPD, we found a negative correlation between FAM13A and p21 protein levels. In ALI-differentiated AECs, the paraquat-induced decrease in expression was accompanied by increased expression. In 16HBE cells, the overexpression of FAM13A significantly reduced paraquat-induced expression and mitochondrial ROS production. Our data suggest that expression decreases with aging, resulting in higher expression and mitochondrial ROS production in the airway epithelium, thus facilitating cellular senescence and as such potentially contributing to accelerated lung aging in COPD. To our knowledge, this is the first study investigating the role of the COPD susceptibility gene FAM13A in aging and cellular senescence. We found that FAM13A negatively regulates the expression of the cellular senescence marker P21 and mitochondrial ROS production in the airway epithelium. In this way, the lower expression of FAM13A observed upon aging may facilitate cellular senescence and potentially contribute to accelerated lung aging in COPD.
Topics: Humans; Reactive Oxygen Species; Paraquat; Pulmonary Disease, Chronic Obstructive; Epithelial Cells; Cellular Senescence; GTPase-Activating Proteins
PubMed: 37605846
DOI: 10.1152/ajplung.00141.2023 -
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