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BMJ Case Reports Nov 2021
Topics: Humans; Paraquat; Poisoning
PubMed: 34764128
DOI: 10.1136/bcr-2021-246585 -
Biochimica Et Biophysica Acta.... Sep 2022Paraquat is a quaternary nitrogen herbicide evoking mitochondrial damage and heart failure with little therapeutic remedies available. Recent reports depicted a role for...
Paraquat is a quaternary nitrogen herbicide evoking mitochondrial damage and heart failure with little therapeutic remedies available. Recent reports depicted a role for unchecked autophagy in paraquat-induced cardiotoxicity. This study was designed to examine the role of the mitophagy receptor protein FUNDC1 in paraquat-induced cardiac contractile and mitochondrial injury using a murine model of FUNDC1 knockout (FUNDC1) mice. WT and FUNDC1 mice were challenged with paraquat (45 mg/kg, single injection, i.p.) for 72 h prior to examination of cardiac contractile and intracellular Ca properties, mitochondrial integrity, mitochondrial function, O production, apoptosis, autosis and ferroptosis. Our results found that paraquat challenge compromised echocardiographic, contractile and intracellular Ca properties in conjunction with mitochondrial damage (reduced levels of PGC1α, UCP2, NAD+, and citrate synthase activity along with fragmentation manifested by elevated Drp1 and TEM ultrastructural changes), the effects of which were overtly attenuated or obliterated by FUNDC1 ablation. Paraquat triggered ferroptosis, apoptosis (but not autosis) and unchecked mitophagy as evidenced by downregulation of GPx4, SLC7A11, Bcl2, TOM20 and ferritin as well as upregulated levels of Bax, TNFα, IL6, NCOA4 and FUNDC1, the effects of which were relieved by FUNDC1 ablation. Further study noted dephosphorylation of JNK upon paraquat challenge, the effect of which was obliterated by FUNDC1 knockout. In vitro evaluation of BODIPY ferroptosis and cardiomyocyte function revealed FUNDC1 ablation inhibited paraquat-induced increase in BODIPY lipid peroxidation and cardiomyocyte contractile dysfunction, the effects of which were nullified and mimicked by inhibition of JNK or ferroptosis and activation of JNK, respectively. Taken together, our data suggest an essential role for FUNDC1/JNK-mediated ferroptosis in paraquat exposure-evoked cardiac and mitochondrial injury.
Topics: Animals; Ferroptosis; Membrane Proteins; Mice; Mice, Knockout; Mitochondrial Proteins; Mitophagy; Myocardium; Myocytes, Cardiac; Paraquat
PubMed: 35598771
DOI: 10.1016/j.bbadis.2022.166448 -
Plant, Cell & Environment Jul 2022Adaptation of higher plants to extreme environmental conditions is under complex regulation. Several small peptides have recently been described to modulate responses to...
Adaptation of higher plants to extreme environmental conditions is under complex regulation. Several small peptides have recently been described to modulate responses to stress conditions. The Small Paraquat resistance protein (SPQ) of Lepidium crassifolium has previously been identified due to its capacity to confer paraquat resistance to overexpressing transgenic Arabidopsis plants. Here, we show that overexpression of the closely related Arabidopsis SPQ can also enhance resistance to paraquat, while the Arabidopsis spq1 mutant is slightly hypersensitive to this herbicide. Besides being implicated in paraquat response, overexpression of SPQs enhanced sensitivity to abscisic acid (ABA), and the knockout spq1 mutant was less sensitive to ABA. Both Lepidium- and Arabidopsis-derived SPQs could improve drought tolerance by reducing water loss, stabilizing photosynthetic electron transport and enhancing plant viability and survival in a water-limited environment. Enhanced drought tolerance of SPQ-overexpressing plants could be confirmed by characterizing various parameters of growth, morphology and photosynthesis using an automatic plant phenotyping platform with RGB and chlorophyll fluorescence imaging. Our results suggest that SPQs can be regulatory small proteins connecting ROS and ABA regulation and through that influence responses to certain stresses.
Topics: Abscisic Acid; Arabidopsis; Arabidopsis Proteins; Droughts; Gene Expression Regulation, Plant; Lepidium; Paraquat; Plants, Genetically Modified; Stress, Physiological; Transcription Factors; Water
PubMed: 35486392
DOI: 10.1111/pce.14338 -
British Journal of Clinical Pharmacology Nov 2011Poisoning by paraquat herbicide is a major medical problem in parts of Asia while sporadic cases occur elsewhere. The very high case fatality of paraquat is due to... (Review)
Review
Poisoning by paraquat herbicide is a major medical problem in parts of Asia while sporadic cases occur elsewhere. The very high case fatality of paraquat is due to inherent toxicity and lack of effective treatments. We conducted a systematic search for human studies that report toxicokinetics, mechanisms, clinical features, prognosis and treatment. Paraquat is rapidly but incompletely absorbed and then largely eliminated unchanged in urine within 12-24 h. Clinical features are largely due to intracellular effects. Paraquat generates reactive oxygen species which cause cellular damage via lipid peroxidation, activation of NF-κB, mitochondrial damage and apoptosis in many organs. Kinetics of distribution into these target tissues can be described by a two-compartment model. Paraquat is actively taken up against a concentration gradient into lung tissue leading to pneumonitis and lung fibrosis. Paraquat also causes renal and liver injury. Plasma paraquat concentrations, urine and plasma dithionite tests and clinical features provide a good guide to prognosis. Activated charcoal and Fuller's earth are routinely given to minimize further absorption. Gastric lavage should not be performed. Elimination methods such as haemodialysis and haemoperfusion are unlikely to change the clinical course. Immunosuppression with dexamethasone, cyclophosphamide and methylprednisolone is widely practised, but evidence for efficacy is very weak. Antioxidants such as acetylcysteine and salicylate might be beneficial through free radical scavenging, anti-inflammatory and NF-κB inhibitory actions. However, there are no published human trials. The case fatality is very high in all centres despite large variations in treatment.
Topics: Aluminum Compounds; Antidotes; Charcoal; Herbicides; Humans; Immunosuppressive Agents; Intestinal Absorption; Magnesium Compounds; Paraquat; Poisoning; Silicates; Survival Rate
PubMed: 21615775
DOI: 10.1111/j.1365-2125.2011.04026.x -
Molecular Neurobiology Jun 2022Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the cardinal features of tremor, bradykinesia, rigidity, and postural instability,... (Review)
Review
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the cardinal features of tremor, bradykinesia, rigidity, and postural instability, in addition to other non-motor symptoms. Pathologically, PD is attributed to the loss of dopaminergic neurons in the substantia nigra pars compacta, with the hallmark of the presence of intracellular protein aggregates of α-synuclein in the form of Lewy bodies. The pathogenesis of PD is still yet to be fully elucidated due to the multifactorial nature of the disease. However, a myriad of studies has indicated several intracellular events in triggering apoptotic neuronal cell death in PD. These include oxidative stress, mitochondria dysfunction, endoplasmic reticulum stress, alteration in dopamine catabolism, inactivation of tyrosine hydroxylase, and decreased levels of neurotrophic factors. Laboratory studies using the herbicide paraquat in different in vitro and in vivo models have demonstrated the induction of many PD pathological features. The selective neurotoxicity induced by paraquat has brought a new dawn in our perspectives about the pathophysiology of PD. Epidemiological data have suggested an increased risk of developing PD in the human population exposed to paraquat for a long term. This model has opened new frontiers in the quest for new therapeutic targets for PD. The purpose of this review is to synthesize the relationship between the exposure of paraquat and the pathogenesis of PD in in vitro and in vivo models.
Topics: Apoptosis; Dopaminergic Neurons; Humans; Nerve Degeneration; Paraquat; Parkinson Disease; Substantia Nigra
PubMed: 35306641
DOI: 10.1007/s12035-022-02799-2 -
Clinical Journal of the American... Sep 2022The etiology of chronic kidney disease of unclear etiology, also known as Mesoamerican nephropathy, remains unclear. We investigated potential etiologies for...
BACKGROUND AND OBJECTIVES
The etiology of chronic kidney disease of unclear etiology, also known as Mesoamerican nephropathy, remains unclear. We investigated potential etiologies for Mesoamerican nephropathy in an immigrant dialysis population.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
Migrants with Mesoamerican nephropathy kidney failure (=52) were identified by exclusion of known causes of kidney disease and compared using a cross-sectional survey with demographically similar patients with kidney failure from other causes (=63) and age/sex/place of origin-matched healthy participants (=16). Survey results were extended to the bench; C57BL/6 mice (=73) received 10-15 weekly intraperitoneal injections of paraquat (a reactive oxygen species-generating herbicide) or vehicle. Kidney function, histology, and expression of organic cation transporter-2 (proximal tubule entry for paraquat) and multidrug and toxin extrusion 1 (extrusion pathway) were examined. Kidney biopsies from Nicaraguan patients with acute Mesoamerican nephropathy were stained for the above transporters and compared with patients with tubulointerstitial nephritis and without Mesoamerican nephropathy.
RESULTS
Patients with Mesoamerican nephropathy and kidney failure were young agricultural workers, almost exclusively men; the majority were from Mexico and El Salvador; and they had prior exposures to agrochemicals, including paraquat (27%). After adjustment for age/sex, exposure to any agrochemical or paraquat was associated with Mesoamerican nephropathy kidney failure (odds ratio, 4.86; 95% confidence interval, 1.82 to 12.96; =0.002 and odds ratio, 12.25; 95% confidence interval, 1.51 to 99.36; =0.02, respectively). Adjusted for age/sex and other covariates, 1 year of agrochemical exposure was associated with Mesoamerican nephropathy kidney failure (odds ratio, 1.23; 95% confidence interval, 1.04 to 1.44; =0.02). Compared with 16 matched healthy controls, Mesoamerican nephropathy kidney failure was significantly associated with exposure to paraquat and agrochemicals. Paraquat-treated male mice developed kidney failure and tubulointerstitial nephritis consistent with Mesoamerican nephropathy. Organic cation transporter-2 expression was higher in male kidneys versus female kidneys. Paraquat treatment increased organic cation transporter-2 expression and decreased multidrug and toxin extrusion 1 expression in male kidneys; similar results were observed in the kidneys of Nicaraguan patients with Mesoamerican nephropathy.
CONCLUSIONS
Exposure to agrochemicals is associated with Mesoamerican nephropathy, and chronic exposure of mice to paraquat, a prototypical oxidant, induced kidney failure similar to Mesoamerican nephropathy.
Topics: Male; Female; Animals; Mice; Paraquat; Cross-Sectional Studies; Mice, Inbred C57BL; Renal Insufficiency, Chronic; Nephritis, Interstitial; Renal Insufficiency; Chronic Kidney Diseases of Uncertain Etiology; Agrochemicals; Cations
PubMed: 35944911
DOI: 10.2215/CJN.16831221 -
Environmental Research Apr 2016Paraquat and diquat are among the most commonly used herbicides in the world.
BACKGROUND
Paraquat and diquat are among the most commonly used herbicides in the world.
OBJECTIVES
Determine the magnitude, characteristics, and root causes for acute paraquat- and diquat-related illnesses in the US METHODS: Illnesses associated with paraquat or diquat exposure occurring from 1998 through 2011 were identified from the Sentinel Event Notification System for Occupational Risks (SENSOR)-Pesticides Program, the California Department of Pesticide Regulation (CDPR) Pesticide Illness Surveillance Program (PISP), and the Incident Data System (IDS). Cases identified by the National Poison Data System (NPDS) were reviewed for the years 1998-2003 and 2006-2013.
RESULTS
A total of 300 paraquat- and 144 diquat-related acute illnesses were identified by SENSOR, PISP, and IDS. NPDS identified 693 paraquat- and 2128 diquat-related acute illnesses. In SENSOR/PISP/IDS, illnesses were commonly low severity (paraquat=41%; diquat=81%); however, SENSOR/PISP/IDS identified 24 deaths caused by paraquat and 5 deaths associated with diquat. Nineteen paraquat-related deaths were due to ingestion, seven of which were unintentional, often due to improper storage in beverage bottles. In SENSOR/PISP/IDS, paraquat and diquat-related acute illnesses were work-related in 68% (n=203) and 29% (n=42) of cases, respectively. When herbicide application site was known, the vast majority of acute paraquat-related illnesses (81%) arose from agricultural applications. Common root causes of illness were failure to use adequate personal protective equipment (PPE), application equipment failure, and spill/splash of herbicide.
CONCLUSIONS
Although the magnitude of acute paraquat/diquat-related illnesses was relatively low, several fatalities were identified. Many illnesses could be prevented through stricter compliance with label requirements (e.g. ensuring proper herbicide storage and PPE use), and through enhanced training of certified applicators.
Topics: Accidents, Occupational; Adolescent; Adult; Aged; Child; Diquat; Environmental Exposure; Female; Herbicides; Humans; Infant; Male; Middle Aged; Occupational Exposure; Paraquat; United States; Young Adult
PubMed: 26775000
DOI: 10.1016/j.envres.2016.01.003 -
International Journal of Environmental... Mar 2021Extensive use of herbicides is common among rural agricultural workers in Sri Lanka. Recent studies have postulated their role in the development of chronic kidney...
Extensive use of herbicides is common among rural agricultural workers in Sri Lanka. Recent studies have postulated their role in the development of chronic kidney disease of unknown etiology (CKDu). Paraquat and glyphosate are leading herbicides used by sugarcane farmers (SF), hence occupational exposure is inevitable. This study examined the expression of urinary paraquat, glyphosate and biomarkers among residential SF in CKDu emerging regions, Warunagama (WA) and Rahathangama (RH), in the Uva Province with non-endemic Matara (MA) in the Southern Province of Sri Lanka. Urinary glyphosate, Paraquat, kidney injury molecule -1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) and β2-microglobulin (B2M) were determined using enzyme-linked immunosorbent assays (ELISA). Urinary creatinine, microalbumin, serum creatinine (SCr), serum cystatin C, estimated glomerular filtration rate (eGFR), and albumin creatinine ratio (ACR) were also assessed. Generally, herbicide residues and kidney injury biomarkers were higher in SF compared to the non-endemic MA. Creatinine-adjusted urinary glyphosate and paraquat levels were significantly higher in WA compared to MA. ACR in RH (median 14.9; IQR 5.4-393.1 mg/g) and WA (23.7; 11.5-64.6) was significantly higher than MA (4.3; 2.2-6.7). This study reports 39 individuals with impaired kidney function among SF in Sri Lanka for the first time. Urinary NGAL levels were significantly higher in both WA (median 2.14; IQR 1.28-6.15 ng/mg Cr) and RH (3.09; 1.15-9.09) compared to MA (1.28; 0.56-2.81). However, urinary KIM-1 levels in RH (3.2; 1.29-106.1 ng/g Cr) and WA (3.6; 1.94-115.1) were not significantly higher in MA (1.74; 0.76-116.9). Urinary NGAL (r = 0.493), eGFR (r = -0.147) and ACR (r = 0.171) significantly correlated with urinary glyphosate, but not with urinary paraquat levels. Urinary KIM-1 levels did not correlate with either urinary glyphosate or paraquat, while urinary B2M and serum cystatin C levels showed significant correlation with urinary glyphosate levels. The current study reports higher urinary herbicide levels among sugarcane farmers in WA and RH, and that is potentially linked to the subsequent decline in kidney function, as indicated by ACR, eGFR, and NGAL. We posit that these indicators may serve as markers to detect renal injury among herbicide-exposed SF in Rural Sri Lanka.
Topics: Agriculture; Biomarkers; Creatinine; Glycine; Humans; Paraquat; Sri Lanka; Glyphosate
PubMed: 33810013
DOI: 10.3390/ijerph18063278 -
Forensic Toxicology Jan 2022Paraquat and diquat are well-known toxic herbicides, at least responsible for hundreds of fatal poisoning events worldwide. However, the determination of diquat and...
Development and validation of a sensitive and high throughput UPLC-MS/MS method for determination of paraquat and diquat in human plasma and urine: application to poisoning cases at emergency departments of hospitals.
PURPOSE
Paraquat and diquat are well-known toxic herbicides, at least responsible for hundreds of fatal poisoning events worldwide. However, the determination of diquat and paraquat in plasma and urine is very challenging because of their high polarity and double charge characteristics. In this study, we aim to develop a rapid and reliable method for the determination of paraquat and diquat in human plasma and urine by ultraperformance liquid chromatography-tandem mass spectrometry.
METHOD
The chromatographic separation of paraquat and diquat was tested with different chromatographic columns and different mobile phase conditions. The mass parameters were optimized by product ions, source gas flow, cone flow, desolvation temperature, and capillary voltage. The isocratic elution mode gave rapid appearance of peak of paraquat and diquat.
RESULTS
The sharp peak shapes for paraquat and diquat were achieved with CORTECS UPLC HILIC (100 × 2.1 mm, 1.6 μm) column by adding formic acid and ammonium acetate in mobile phase in isocratic elution mode. The lower limit of quantification of 1.0 ng/mL for paraquat and diquat were achieved using only 50 μL of human plasma or urine. The running time for analysis of both paraquat and diquat was as short as 3.5 min per sample.
CONCLUSIONS
A rapid and reliable method for the determination of paraquat and diquat was developed and applied to 387 clinical poisoning cases and 22 poisoning cases were found to be paraquat or diquat poisoning.
Topics: Humans; Diquat; Paraquat; Tandem Mass Spectrometry; Chromatography, Liquid; Chromatography, High Pressure Liquid; Hospitals; Emergency Service, Hospital
PubMed: 36454496
DOI: 10.1007/s11419-021-00603-9 -
Science Progress 2021The aquatic ecosystem is under increasing pressure from environmental contaminants due to anthropogenic activities. This study investigated the potential of glyphosate...
The aquatic ecosystem is under increasing pressure from environmental contaminants due to anthropogenic activities. This study investigated the potential of glyphosate and paraquat to induce DNA damage and other cell abnormalities in juvenile African Catfish, . Juvenile fish were exposed for 96 h to 0.36, 0.48, 0.60, 0.72 and 0.84 mg/L glyphosate; and 0.018, 0.037, 0.055, 0.110 and 0.221 mg/L paraquat. Following the exposure, the fish liver and blood were analysed for DNA damage and micronucleus respectively. DNA damage was analysed using comet assay while the micronucleus test was used for assessing nuclear abnormalities. Both herbicides induced DNA damage in fish, with paraquat exhibiting higher toxicity. The severity in liver DNA damage was observed to be dependent on concentration. The herbicides triggered formation of micronuclei, bean-shaped cells, lobed nuclei, and apoptosis in blood cells of fish. Both herbicides also increased the frequency of occurrence of these cell abnormalities in erythrocytes and showed mutagenic potential in fish. Glyphosate and Paraquat both have mutagenic potentials in fish and this is a reflection of the threat these contaminants pose to fish and other forms of aquatic life in our natural water bodies. Low concentrations of these herbicides should be encouraged when usage is inevitable.
Topics: Animals; Catfishes; DNA Damage; Ecosystem; Glycine; Herbicides; Mutagens; Paraquat; Water Pollutants, Chemical; Glyphosate
PubMed: 34148463
DOI: 10.1177/00368504211021751