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Medicine Feb 2020Severity index and plasma paraquat (PQ) concentration can predict the prognosis of patients with PQ poisoning. However, the better parameter is yet to be systematically... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Severity index and plasma paraquat (PQ) concentration can predict the prognosis of patients with PQ poisoning. However, the better parameter is yet to be systematically investigated and determined. Thus, we conduct this systematic review and meta-analysis to investigate the prognostic value of severity index and plasma PQ concentration in patients with PQ poisoning.
METHODS
We searched PubMed, Embase, Web of Science, ScienceDirect, and Cochrane Library to identify all relevant papers that were published up to March 2019. All diagnostic studies that compared severity index and plasma PQ concentration to predict mortality in patients with PQ poisoning were enrolled in this meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) for individual trials were pooled using a random-effect model. We also aggregated heterogeneity testing, sensitivity analysis, and publication bias analysis.
RESULTS
Ultimately, seven studies involving 821 patients were included. The pooled OR with a 95% CI of severity index was 24.12 (95% CI: 9.34-62.34, P < .001), with an area under the curve of 0.88 (95% CI: 0.85-0.90), sensitivity of 0.84 (95% CI: 0.74-0.91), and specificity of 0.81 (95% CI: 0.75-0.87). Meanwhile, the pooled OR with 95% CI of plasma PQ concentration was 34.39 (95% CI: 14.69-80.56, P < .001), with an area under the curve of 0.94 (95% CI: 0.91-0.96), sensitivity of 0.86 (95% CI: 0.75-0.93), and specificity of 0.89 (95% CI: 0.76-0.95). Sensitivity analysis demonstrated the stability of the results of our meta-analysis. No significant publication bias was observed in this meta-analysis.
CONCLUSION
Overall, this study indicated that severity index and plasma PQ concentration have relatively high-prognostic value in patients with PQ poisoning, and that the sensitivity and specificity of plasma PQ concentration are superior to those of severity index.
Topics: Humans; Paraquat; Poisoning; Predictive Value of Tests; Severity of Illness Index
PubMed: 32028427
DOI: 10.1097/MD.0000000000019063 -
Zeitschrift Fur Naturforschung. C,... 2001The paper gives an overview of literature on paraquat resistance of weeds and the proposed mechanism of resistance. New results we achieved on horseweed (Conyza... (Comparative Study)
Comparative Study Review
The paper gives an overview of literature on paraquat resistance of weeds and the proposed mechanism of resistance. New results we achieved on horseweed (Conyza canadensis /L./, Cronq.) are discussed in detail. It was demonstrated that there is no significant constitutive difference related to the paraquat resistance between untreated susceptible and paraquat-resistant horseweed plants. The lower sensitivity of flowering resistant plants may be due to the fact that paraquat content in treated leaves of flowering resistant plants was only 25% as compared to those measured at rosette stage. Our results confirm that paraquat resistance is not based on elevated level and activity of antioxidant enzyme system. The hypothesized role of polyamines in the resistance mechanisms can be excluded. The higher putrescine and total polyamine content of paraquat treated resistant leaves can rather be regarded as a general stress response, than as a symptom of paraquat resistance. A paraquat-inducible protein is supposed to play a role in the resistance, which presumably functions by binding paraquat to an inactivating site and/or by carrying paraquat to metabolically inactive cell compartment (vacuole, cell wall). From model experiments it is concluded that paraquat and diquat preferentially form hydrophylic interactions with proteins containing a higher amount of lysine and glutamic acid. Consequently, the reason for paraquat resistance in horseweed is probably a hydrophylic interaction of paraquat with a protein, leading to inactivation of paraquat through forming a conjugate and/or sequestration into the vacuole or the cell wall.
Topics: Asteraceae; Drug Resistance; Herbicides; Paraquat; Poaceae
PubMed: 11421444
DOI: 10.1515/znc-2001-5-601 -
Lung Oct 2022Pulmonary fibrosis is a life-threatening lung disorder. A comprehensive understanding of the pathophysiological changes in the development of pulmonary fibrosis will...
PURPOSE
Pulmonary fibrosis is a life-threatening lung disorder. A comprehensive understanding of the pathophysiological changes in the development of pulmonary fibrosis will lead to new insights into its treatment.
METHODS
We used a paraquat (PQ)-induced rhesus monkey model of pulmonary fibrosis to comprehensively investigate the process of pulmonary fibrosis development. Rhesus monkeys were orally administered PQ at concentrations of 25 mg/kg, 40 mg/kg, and 80 mg/kg. The dose was given once. Behavior and clinical data, such as PQ concentration, arterial oxygen saturation, biochemical evaluation, lung histopathology, and medical imaging, were continuously observed.
RESULTS
Paraquat-exposed monkeys developed pulmonary fibrosis following an expected time course, especially at 25 mg/kg. CT images showed ground-glass lesions in the lung after 4 weeks, and pulmonary fibrosis persisted until the end of follow-up. Using pathological examination, the lung sustained collagen deposition and slight inflammatory cell infiltration. All rhesus monkeys had obvious inflammatory infiltration within 1 week according to the immunohistochemical results and the number of leukocytes in the blood. The CT results showed that pulmonary fibrosis had not formed, indicating that drugs with powerful anti-inflammatory ability are potential candidates for early pulmonary fibrosis treatment.
CONCLUSION
Our study describes the dynamic process of paraquat-induced pulmonary fibrosis in rhesus monkeys and provided a pathophysiological basis for the treatment of pulmonary fibrosis.
Topics: Animals; Collagen; Lung; Macaca mulatta; Paraquat; Pulmonary Fibrosis
PubMed: 36163517
DOI: 10.1007/s00408-022-00572-9 -
Aging Cell Feb 2024A major goal of healthy aging is to prevent declining resilience and increasing frailty, which are associated with many chronic diseases and deterioration of stress...
A major goal of healthy aging is to prevent declining resilience and increasing frailty, which are associated with many chronic diseases and deterioration of stress response. Here, we propose a loss-or-gain survival model, represented by the ratio of cumulative stress span to life span, to quantify stress resilience at organismal level. As a proof of concept, this is demonstrated by reduced survival resilience in Caenorhabditis elegans exposed to exogenous oxidative stress induced by paraquat or with endogenous proteotoxic stress caused by polyglutamine or amyloid-β aggregation. Based on this, we reveal that a hidden peptide ("cryptide")-AbaPep#07 (SETYELRK)-derived from abalone hemocyanin not only enhances survival resilience against paraquat-induced oxidative stress but also rescues proteotoxicity-mediated behavioral deficits in C. elegans, indicating its capacity against stress and neurodegeneration. Interestingly, AbaPep#07 is also found to increase cost-free longevity and age-related physical fitness in nematodes. We then demonstrate that AbaPep#07 can promote nuclear localization of SKN-1/Nrf, but not DAF-16/FOXO, transcription factor. In contrast to its effects in wild-type nematodes, AbaPep#07 cannot increase oxidative stress survival and physical motility in loss-of-function skn-1 mutant, suggesting an SKN-1/Nrf-dependent fashion of these effects. Further investigation reveals that AbaPep#07 can induce transcriptional activation of immune defense, lipid metabolism, and metabolic detoxification pathways, including many SKN-1/Nrf target genes. Together, our findings demonstrate that AbaPep#07 is able to boost stress resilience and reduce behavioral frailty via SKN-1/Nrf-governed transcriptional reprogramming, and provide an insight into the health-promoting potential of antioxidant cryptides as geroprotectors in aging and associated conditions.
Topics: Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; DNA-Binding Proteins; Frailty; Longevity; Metabolic Reprogramming; Oxidative Stress; Paraquat; Peptides; Resilience, Psychological
PubMed: 37990605
DOI: 10.1111/acel.14046 -
Ecotoxicology and Environmental Safety Nov 2023In the environmental safety area, the widespread use of the herbicide Paraquat (PQ) poses a great threat to hydrobionts and mammals. Due to the lack of specific...
In the environmental safety area, the widespread use of the herbicide Paraquat (PQ) poses a great threat to hydrobionts and mammals. Due to the lack of specific antidote, it may lead to irreversible pulmonary fibrosis with a mortality rate of 60%. Therefore, it is necessary to develop an effective and specific PQ antidote. The g-CN (HPCN) with excellent surface physicochemical properties was prepared by a two-step calcination method using urea and dicyandiamide as raw materials, showing a significant photocatalyst against environmental PQ pollution. The SEM results showed that HPCN possesses a porous layered structure. X-ray diffraction and infrared spectroscopy indicated that the conjugated aromatic rings were orderly stacked, forming a 2D layered structure of g-CN. The HPCN had a larger specific surface area (56.84 m g) and pore volume (0.2718 cm g), which enhanced its adsorption capacity and photocatalytic activity. HPCN exhibited an effective adsorption rate of 38.25% for PQ in water under light. Compared with the PQ group (54.8%), the cell viability of the HPCN group (91.4%) significantly increased by 36.6%, and the SEM observation revealed the restoration of normal cell morphology. The HPCN effectively reduced PQ content in zebrafish and mice in vivo, resulting in an approximately 70% increase in survival rate. The UV-Vis results indicated that the adsorption rate of HPCN for PQ in zebrafish was 43.5%. The enhanced catalytic performance of HPCN provides a promising solution for the detoxification of PQ and of other environmental pollutants.
Topics: Animals; Mice; Paraquat; Zebrafish; Antidotes; Herbicides; Pulmonary Fibrosis; Mammals
PubMed: 37856982
DOI: 10.1016/j.ecoenv.2023.115594 -
Acta Medica Portuguesa 1989The authors review the mechanisms of paraquat and diquat toxicity. They discuss the generation of multiple toxic active forms of oxygen. The pulmonary concentration of... (Review)
Review
The authors review the mechanisms of paraquat and diquat toxicity. They discuss the generation of multiple toxic active forms of oxygen. The pulmonary concentration of paraquat seems to be due to a mechanism of active concentration, which seems to be used by polyamines and diamines in normal situations. Considerations on therapeutics attempts are made.
Topics: Animals; Diquat; Free Radicals; Kidney; Liver; Lung; Oxidation-Reduction; Paraquat; Pyridinium Compounds; Superoxides
PubMed: 2549765
DOI: No ID Found -
Chemico-biological Interactions Nov 2010Pesticides are widely used in agricultural and other settings, resulting in continued human exposure. Pesticide toxicity has been clearly demonstrated to alter a variety... (Review)
Review
Pesticides are widely used in agricultural and other settings, resulting in continued human exposure. Pesticide toxicity has been clearly demonstrated to alter a variety of neurological functions. Particularly, there is strong evidence suggesting that pesticide exposure predisposes to neurodegenerative diseases. Epidemiological data have suggested a relationship between pesticide exposure and brain neurodegeneration. However, an increasing debate has aroused regarding this issue. Paraquat is a highly toxic quaternary nitrogen herbicide which has been largely studied as a model for Parkinson's disease providing valuable insight into the molecular mechanisms involved in the toxic effects of pesticides and their role in the progression of neurodegenerative diseases. In this work, we review the molecular mechanisms involved in the neurotoxic action of pesticides, with emphasis on the mechanisms associated with the induction of neuronal cell death by paraquat as a model for Parkinsonian neurodegeneration.
Topics: Animals; Humans; Neurodegenerative Diseases; Neurons; Oxidative Stress; Paraquat; Parkinson Disease, Secondary; Pesticides
PubMed: 20542017
DOI: 10.1016/j.cbi.2010.06.003 -
PloS One 2018Paraquat (PQ) poisoning can cause multiple organ failure, in which the lung is the primary target organ. There is currently no treatment for PQ poisoning. Mesenchymal... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Paraquat (PQ) poisoning can cause multiple organ failure, in which the lung is the primary target organ. There is currently no treatment for PQ poisoning. Mesenchymal stem cells (MSCs), which differentiate into multiple cell types, have generated much enthusiasm regarding their use for the treatment of several diseases. The aim of this study was to systematically review and analyze published preclinical studies describing MSC administration for the treatment of PQ poisoning in animal models to provide a basis for cell therapy.
METHODS
The electronic databases PubMed and CBMdisc were searched in this systematic review and meta-analysis. The MSC treatment characteristics of animal models of PQ poisoning were summarized. After quality assessment was performed, the effects of MSC transplantation were evaluated based on the survival rate, lung wet/dry weight, fibrosis scores, oxidative stress response, and inflammatory response. Publication bias was assessed.
RESULTS
Eleven controlled preclinical studies involving MSC transplantation in animal models of PQ poisoning were included in this review. MSC therapy improved the survival rate and reduced the lung wet/dry weight and histopathological fibrosis changes in most studies. MSCs decreased serum or plasma malondialdehyde levels in the acute phase after 7 and 14 d and increased serum or plasma superoxide dismutase and glutathione levels at the same time points. IL-1β, TNF-α and TGF-β1 levels in blood or lung tissues were decreased to different degrees by MSCs. Lung hydroxyproline was decreased by MSCs after 14 d. No obvious evidence of publication bias was found.
CONCLUSION
MSCs showed anti-fibrosis therapeutic effects in animal models of lung injury caused by PQ poisoning, which may be related to reduced oxidative stress and inflammatory cytokine levels. Our review indicates a potential therapeutic role for MSC therapy to treat PQ poisoning and serves to augment the rationale for clinical studies.
Topics: Acute Lung Injury; Animals; Disease Models, Animal; Evaluation Studies as Topic; Humans; Mesenchymal Stem Cell Transplantation; Paraquat; Pulmonary Edema
PubMed: 29566055
DOI: 10.1371/journal.pone.0194748 -
Communications Biology Oct 2022Paraquat (PQ) is an efficient herbicide but leads to high mortality with no antidote in mammals. PQ produces reactive oxygen species (ROS), leading to...
Paraquat (PQ) is an efficient herbicide but leads to high mortality with no antidote in mammals. PQ produces reactive oxygen species (ROS), leading to epithelial-mesenchymal transition (EMT) for pulmonary fibrosis in type II alveolar (AT II) cells. Intriguingly, strategies reducing ROS exhibit limited therapeutic effects, indicating other targets existing for PQ toxicity. Herein we report that PQ is also an agonist for STIM1 that increases intracellular calcium levels. Particularly, PQ promotes STIM1 puncta formation and association with TRPC1 or ORAI for extracellular calcium entry and thus intracellular calcium influx. Further studies reveal the importance of P584&Y586 residues in STIM1 for PQ association that facilitates STIM1 binding to TRPC1. Consequently, the STIM1-TRPC1 route facilitates PQ-induced EMT for pulmonary fibrosis as well as cell death. Our results demonstrate that PQ is an agonist of STIM1 that induces extracellular calcium entry, increases intracellular calcium levels, and thus promotes EMT in AT II cells.
Topics: Animals; Paraquat; Pulmonary Fibrosis; Calcium; Reactive Oxygen Species; Epithelial-Mesenchymal Transition; Mammals
PubMed: 36310238
DOI: 10.1038/s42003-022-04130-0 -
Journal of Neuroinflammation Jun 2019Leucine-rich repeat kinase 2 (LRRK2) is a common gene implicated in Parkinson's disease (PD) and is also thought to be fundamentally involved in numerous immune...
BACKGROUND
Leucine-rich repeat kinase 2 (LRRK2) is a common gene implicated in Parkinson's disease (PD) and is also thought to be fundamentally involved in numerous immune functions. Thus, we assessed the role of LRRK2 in the context of the effects of the environmental toxicant, paraquat, that has been implicated in PD and is known to affect inflammatory processes.
METHODS
Male LRRK2 knockout (KO) and transgenic mice bearing the G2019S LRRK2 mutation (aged 6-8 months) or their littermate controls were exposed to paraquat (two times per week for 3 weeks), and sickness measures, motivational scores, and total home-cage activity levels were assessed. Following sacrifice, western blot and ELISA assays were performed to see whether or not LRRK2 expression would alter processes related to plasticity, immune response processes, or the stress response.
RESULTS
Paraquat-induced signs of sickness, inflammation (elevated IL-6), and peripheral toxicity (e.g., organ weight) were completely prevented by LRRK2 knockout. In fact, LRRK2 knockout dramatically reduced not only signs of illness, but also the motivational (nest building) and home-cage activity deficits induced by paraquat. Although LRRK2 deficiency did not affect the striatal BDNF reduction that was provoked by paraquat, it did blunt the corticosterone elevation induced by paraquat, raising the possibility that LRRK2 may modulate aspects of the HPA stress axis. Accordingly, we found that transgenic mice bearing the G2019S LRRK2 mutation had elevated basal corticosterone, along with diminished hippocampal 5-HT1A levels.
CONCLUSION
We are the first to show the importance of LRRK2 in the peripheral neurotoxic and stressor-like effects of paraquat. These data are consistent with LRRK2 playing a role in the general inflammatory tone and stressor effects induced by environmental toxicant exposure.
Topics: Animals; Herbicides; Inflammation; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Paraquat; Phenotype
PubMed: 31174552
DOI: 10.1186/s12974-019-1483-7