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The Journal of International Medical... Jun 2021Diquat 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...
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.
Topics: Adult; Diquat; Herbicides; Humans; Male; Multiple Organ Failure; Paraquat; Respiratory Insufficiency
PubMed: 34182818
DOI: 10.1177/03000605211026117 -
Biological & Pharmaceutical Bulletin Jan 2006Antioxidant effects of extracts from Croton cajucara BENTH. leaves was investigated in different in vitro and in vivo models. Extracts showed inhibitory radical...
Antioxidant effects of extracts from Croton cajucara BENTH. leaves was investigated in different in vitro and in vivo models. Extracts showed inhibitory radical scavenging activity against the stable radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) (75%, 43% and 25% of the standard trolox at 1, 10 and 100 mg/ml, respectively; IC50 218 mg/ml). Percentage survival of Saccharomyces cerevisiae cells treated with 10 mM paraquat increased by 21% and 55%, when 1 mg/ml and 10 mg/ml concentrations of the extract, respectively, were added. The cytosolic concentration of TBARS increased in animals treated with paraquat (+283%), while values did not significantly differ from the controls in rats additionally receiving the leaf extract. Paraquat administration also induced a significant increase in hydroperoxide-initiated chemiluminiscence (+76%), that was partially prevented by the leaf extract (+31%). Liver SOD activity was a 158% higher in animals receiving paraquat as compared to the controls. This effect was abolished by administration of the leaf extract. Paraquat administration did not significantly modify the activity of GPx or catalase. Croton cajucara extract increased GPx and catalase activities in paraquat treated-animals by 342% and 70%, respectively. Our results confirm that Croton cajucara leaf extract present radical scavenging activity and reduce oxidative stress induced by paraquat, suggesting the beneficial use as a potential source of antioxidant agents of natural origin.
Topics: Animals; Biphenyl Compounds; Croton; Free Radical Scavengers; Liver; Luminescent Measurements; Male; Oxidants; Oxidative Stress; Paraquat; Picrates; Plant Extracts; Plant Leaves; Rats; Rats, Wistar; Saccharomyces cerevisiae; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances
PubMed: 16394531
DOI: 10.1248/bpb.29.161 -
Chemical Research in Toxicology Dec 2022Acute and long-term paraquat (PQ) exposure produces hippocampal neurodegeneration and cognition decline. Although some mechanisms involved in these effects were found,...
Insulin Signaling Disruption and INF-γ Upregulation Induce Aβ and Hyperphosphorylated-Tau Proteins Synthesis and Cell Death after Paraquat Treatment of Primary Hippocampal Cells.
Acute and long-term paraquat (PQ) exposure produces hippocampal neurodegeneration and cognition decline. Although some mechanisms involved in these effects were found, the rest are unknown. PQ treatment, for 1 and 14 days, upregulated interferon-gamma signaling, which reduced insulin levels and downregulated the insulin pathway through phosphorylated-c-Jun N-terminal-kinase upregulation, increasing glucose levels and the production of Aβ and phosphorylated-tau, by beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) overexpression and phosphorylated-GSK3β (p-GSK3β; ser9) level reduction, respectively, which induced primary hippocampal neuronal loss. This novel information on the PQ mechanisms leading to hippocampal neurodegeneration could help reveal the PQ actions that lead to cognition dysfunction.
Topics: tau Proteins; Paraquat; Amyloid Precursor Protein Secretases; Glycogen Synthase Kinase 3 beta; Insulin; Up-Regulation; Aspartic Acid Endopeptidases; Amyloid beta-Peptides; Hippocampus; Cell Death
PubMed: 36394833
DOI: 10.1021/acs.chemrestox.2c00278 -
PloS One 2022The objective of this study was to investigate the treatment effects of non-thermal atmospheric gas plasmas (NTAP) on destruction and the recovery (or re-colonization)...
The objective of this study was to investigate the treatment effects of non-thermal atmospheric gas plasmas (NTAP) on destruction and the recovery (or re-colonization) of Porphyromonas gingivalis (P. gingivalis) in biofilms. P. gingivalis is a well-known keystone periodontal pathogen strongly associated with periodontal diseases, especially periodontitis. P. gingivalis biofilms were formed on stainless steel coupons and treated for 1, 2, and 5 minutes by NTAP of pure argon gas and argon+oxygen gas mixture. MTT assay, colony forming unit (CFU) counting assay and confocal laser scanning microscopy (CLSM) were used to assess the destruction efficiency. In addition, the plasma treated biofilms were re-cultured in the medium supplemented with antibiotics and oxidative stress sources to determine the synergy of the NTAP with other antimicrobial agents. The results showed the plasma treatment could result in 2.7 log unit reduction in bacterial load. The recovered biofilm CFU with NTAP treatment combined with sub minimal inhibition concentration of amoxicillin was 0.33 log units less than the biofilm treated with amoxicillin alone. The recovered biofilm CFU in NTAP groups was about 2.0 log units less than that in the untreated controls under H2O2 treatment. There was approximately 1.0 log unit reduction of biofilm CFU in plasma treated biofilm compared with untreated control under paraquat treatment. The plasma treated biofilms exhibited less resistance to amoxicillin and greater susceptibility to hydrogen peroxide (H2O2) and paraquat, suggesting that NTAP may enhance biofilm susceptibility to host defense. These in vitro findings suggested that NTAP could be a novel and effective treatment method of oral biofilms that cause periodontal diseases.
Topics: Amoxicillin; Argon; Biofilms; Humans; Hydrogen Peroxide; Paraquat; Periodontal Diseases; Plasma Gases; Porphyromonas gingivalis
PubMed: 36103549
DOI: 10.1371/journal.pone.0274523 -
Se Pu = Chinese Journal of... Dec 2022Determining the presence of paraquat (PQ) and diquat (DQ) in urine samples through physical and chemical testing is challenging. As PQ and DQ have characteristics such...
[Determination of paraquat and diquat residues in urine samples based on solid-phase extraction and ultra performance liquid chromatography-high resolution mass spectrometry].
Determining the presence of paraquat (PQ) and diquat (DQ) in urine samples through physical and chemical testing is challenging. As PQ and DQ have characteristics such as high molecular polarity and good water solubility, they are difficult to be retained by conventional reversed-phase columns. Most of the methods in the literature use hydrophilic interaction chromatography (HILIC) for the retention of PQ and DQ, but they often require high concentrations of buffer salts as the mobile phase, which increase the contamination of the mass spectrometer. In view of the above problems, a rapid and accurate analysis method was developed for the determination of PQ and DQ residuals in urine samples based on weak cation exchange (WCX) solid-phase extraction (SPE) and ultra performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) in this study. Urine samples were first diluted with phosphate buffer (pH=6.86) and pretreated using the WCX SPE method. Chromatographic separation was performed on a Syncronis HILIC column (100 mm×2.1 mm, 1.7 μm). An electrospray ion source in the positive (ESI) mode and full mass-data dependent MS (full mass-ddMS) mode was used for quantification by matrix-matched external standard method. In this study, the concentration of ammonium formate in the mobile phase in the HILIC mode was effectively reduced to 10 mmol/L by the continuous optimization of the chromatographic conditions. MS optimization results indicated that the molecular ion (M) of PQ and DQ had the strongest response. In addition, sample pretreatment conditions were also optimized. The obtained results indicated that the hydrophobic polytetrafluoroethylene (PTFE) filter membrane, acetonitrile-water (1∶1, v/v) as a fixing solution, and polypropylene vials were suitable for PQ and DQ analysis. Under the optimal conditions, the linearity of PQ and DQ was good with correlation coefficients () greater than 0.998. The limits of detection (LODs, ≥3) and limits of quantification (LOQs, ≥10) were 0.2 μg/L and 0.6 μg/L, respectively. Mean spiked recoveries of PQ and DQ at the four spiked levels (1.0, 20.0, 100.0, and 200.0 μg/L) were in the range of 85.8%-101% and 80.3%-86.9%, with the RSDs of 0.8%-5.1% and 0.9%-4.2%. The established method was employed for the analysis and confirmation of PQ and DQ for clinical poisoning cases. In one case, a 23-year-old male who had taken approximately 20 mL of pesticide orally was confirmed as DQ poisoning by the developed method. DQ concentration monitoring of the urine samples was conducted for this case during the clinical treatment process. The patient was successfully discharged from the hospital after five times of blood perfusion and other treatments until the DQ concentration was low in the urine samples. In conclusion, the method developed in this study based on WCX SPE-UPLC-HRMS can be used for the confirmation of poisoning cases and concentration monitoring during clinical treatment, providing strong technical support for clinical precision treatment. The method is rapid, simple, sensitive, and accurate, and it is suitable for the detection of PQ and DQ in urine samples.
Topics: Male; Humans; Young Adult; Adult; Diquat; Paraquat; Chromatography, Liquid; Mass Spectrometry; Solid Phase Extraction
PubMed: 36450348
DOI: 10.3724/SP.J.1123.2022.02012 -
Kidney International Dec 2018
Topics: Hemoperfusion; Paraquat
PubMed: 30466569
DOI: 10.1016/j.kint.2018.09.003 -
Phytomedicine : International Journal... Apr 2023Acute lung injury (ALI) induced by paraquat (PQ) progresses rapidly, leading to high mortality; however, there is no specific antidote. Our limited knowledge of the...
BACKGROUND
Acute lung injury (ALI) induced by paraquat (PQ) progresses rapidly, leading to high mortality; however, there is no specific antidote. Our limited knowledge of the pathogenic toxicological mechanisms of PQ has hindered the development of treatments against PQ exposure.
PURPOSE
Pyroptosis is a form of programmed cell death recently identified as a novel molecular mechanism adopted by chemotherapeutic drugs for cancer therapy. However, the involvement of pyroptosis in PQ-induced lung injury has not been reported. Therefore, we investigated the effects of PQ on the lung tissues to elucidate the molecular mechanisms underlying its toxicity, especially its ability to induce pyroptosis.
METHODS
To observe the morphological changes of BEAS-2B cells exposed to PQ, the plasma membrane damage of the cells was detected by LDH release assay, mitochondrial function and cell metabolism were detected by energy metabolism analysis. Western blotting was used to detect the protein levels of GSDMD, C-GSDMD, GSDME and N-GSDME in BEAS-2B cells. Metabolites of TCA cycle were detected by metabolomics, and the changes of TCA cycle metabolic enzymes in cells were detected by Western blotting.
RESULTS
We observed that PQ induced proteolytic cleavage of gasdermin E (GSDME) with concomitant cleavage of caspase 3 in BEAS-2B cells. Knockout of GSDME attenuated PQ-induced cell death. Additionally, PQ induced ROS accumulation, mitochondrial depolarisation, and mitochondrial dysfunction in these cells. PQ activated the caspase 3/GSDME pathway and damaged the cytoplasmic membrane in cells, leading to pyroptosis. We demonstrated that DMK suppressed PQ-induced pyroptosis by blocking PQ-induced caspase 3/GSDME pathway activation, reducing cellular ROS levels, and improving mitochondrial function.
CONCLUSION
These findings provide novel insights into the previously unrecognized mechanism of GSDME-dependent pyroptosis in PQ poisoning.
Topics: Pyroptosis; Caspase 3; Paraquat; Ketoglutaric Acids; Reactive Oxygen Species
PubMed: 36773430
DOI: 10.1016/j.phymed.2023.154698 -
Biological & Pharmaceutical Bulletin 2015Paraquat is one of the most widely used herbicides in the world and is highly toxic to humans and animals. In this study, we developed a serum metabolomic method based...
Paraquat is one of the most widely used herbicides in the world and is highly toxic to humans and animals. In this study, we developed a serum metabolomic method based on GC/MS to evaluate the effects of acute paraquat poisoning on rats. Pattern recognition analysis, including both principal component analysis and partial least squares-discriminate analysis revealed that acute paraquat poisoning induced metabolic perturbations. Compared with the control group, the level of octadecanoic acid, L-serine, L-threonine, L-valine, and glycerol in the acute paraquat poisoning group (36 mg/kg) increased, while the levels of hexadecanoic acid, D-galactose, and decanoic acid decreased. These findings provide an overview of systematic responses to paraquat exposure and metabolomic insight into the toxicological mechanism of paraquat. Our results indicate that metabolomic methods based on GC/MS may be useful to elucidate the mechanism of acute paraquat poisoning through the exploration of biomarkers.
Topics: Amino Acids; Animals; Biomarkers; Galactose; Herbicides; Lipid Metabolism; Male; Metabolome; Metabolomics; Paraquat; Rats, Sprague-Dawley
PubMed: 26133715
DOI: 10.1248/bpb.b15-00147 -
The Journal of Pharmacology and... Feb 2014Genetic variation in the multidrug resistance gene ABCB1, which encodes the efflux transporter P-glycoprotein (P-gp), has been associated with Parkinson disease. Our...
Genetic variation in the multidrug resistance gene ABCB1, which encodes the efflux transporter P-glycoprotein (P-gp), has been associated with Parkinson disease. Our goal was to investigate P-gp transport of paraquat, a Parkinson-associated neurotoxicant. We used in vitro transport models of ATPase activity, xenobiotic-induced cytotoxicity, transepithelial permeability, and rhodamine-123 inhibition. We also measured paraquat pharmacokinetics and brain distribution in Friend leukemia virus B-type (FVB) wild-type and P-gp-deficient (mdr1a(-/-)/mdr1b(-/-)) mice following 10, 25, 50, and 100 mg/kg oral doses. In vitro data showed that: 1) paraquat failed to stimulate ATPase activity; 2) resistance to paraquat-induced cytotoxicity was unchanged in P-gp-expressing cells in the absence or presence of P-gp inhibitors GF120918 [N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide] and verapamil-37.0 [95% confidence interval (CI): 33.2-41.4], 46.2 (42.5-50.2), and 34.1 µM (31.2-37.2)-respectively; 3) transepithelial permeability ratios of paraquat were the same in P-gp-expressing and nonexpressing cells (1.55 ± 0.39 and 1.39 ± 0.43, respectively); and 4) paraquat did not inhibit rhodamine-123 transport. Population pharmacokinetic modeling revealed minor differences between FVB wild-type and mdr1a(-/-)/mdr1b(-/-) mice: clearances of 0.47 [95% confidence interval (CI): 0.42-0.52] and 0.78 l/h (0.58-0.98), respectively, and volume of distributions of 1.77 (95% CI: 1.50-2.04) and 3.36 liters (2.39-4.33), respectively; however, the change in clearance was in the opposite direction of what would be expected. It is noteworthy that paraquat brain-to-plasma partitioning ratios and total brain accumulation were the same across doses between FVB wild-type and mdr1a(-/-)/mdr1b(-/-) mice. These studies indicate that paraquat is not a P-gp substrate. Therefore, the association between ABCB1 pharmacogenomics and Parkinson disease is not attributed to alterations in paraquat transport.
Topics: ATP Binding Cassette Transporter, Subfamily B; Animals; Biological Transport; Brain; Capillary Permeability; Cell Line; Cell Survival; Dose-Response Relationship, Drug; Epithelial Cells; Fluorescent Dyes; Herbicides; Male; Membrane Transport Modulators; Mice; Mice, Knockout; Paraquat; Parkinson Disease; Recombinant Proteins; Rhodamine 123; Sus scrofa; Tissue Distribution; ATP-Binding Cassette Sub-Family B Member 4
PubMed: 24297779
DOI: 10.1124/jpet.113.209791 -
Proceedings of the National Academy of... Mar 1977Previous reports of a relatively air-stable soluble hydrogenase from the photosynthetic anaerobe, Chromatium vinosum, have been substantiated. The properties of this...
Previous reports of a relatively air-stable soluble hydrogenase from the photosynthetic anaerobe, Chromatium vinosum, have been substantiated. The properties of this enzyme, as seen in highly purified samples prepared by procedures that permit improved yields, are described. A possible role for flavin mediation is noted.
Topics: Chromatium; Detergents; Flavin Mononucleotide; Molecular Weight; Oxidoreductases; Paraquat; Solubility; Urea
PubMed: 265580
DOI: 10.1073/pnas.74.3.861