-
Drug Research Jun 2024Pentoxifylline (PTX), a non-selective phosphodiesterase inhibitor, has demonstrated protective effects against lung injury in animal models. Given the significance of...
Pentoxifylline (PTX), a non-selective phosphodiesterase inhibitor, has demonstrated protective effects against lung injury in animal models. Given the significance of pulmonary toxicity resulting from paraquat (PQ) exposure, the present investigation was designed to explore the impact of PTX on PQ-induced pulmonary oxidative impairment in male mice.Following preliminary studies, thirty-six mice were divided into six groups. Group 1 received normal saline, group 2 received a single dose of PQ (20 mg/kg; i.p.), and group 3 received PTX (100 mg/kg/day; i.p.). Additionally, treatment groups 4-6 were received various doses of PTX (25, 50, and 100 mg/kg/day; respectively) one hour after a single dose of PQ. After 72 hours, the animals were sacrificed, and lung tissue was collected.PQ administration caused a significant decrease in hematocrit and an increase in blood potassium levels. Moreover, a notable increase was found in the lipid peroxidation (LPO), nitric oxide (NO), and myeloperoxidase (MPO) levels, along with a notable decrease in total thiol (TTM) and total antioxidant capacity (TAC) contents, catalase (CAT) and superoxide dismutase (SOD) enzymes activity in lung tissue. PTX demonstrated the ability to improve hematocrit levels; enhance SOD activity and TTM content; and decrease MPO activity, LPO and NO levels in PQ-induced pulmonary toxicity. Furthermore, these findings were well-correlated with the observed lung histopathological changes.In conclusion, our results suggest that the high dose of PTX may ameliorate lung injury by improving the oxidant/antioxidant balance in animals exposed to PQ.
Topics: Animals; Pentoxifylline; Paraquat; Mice; Male; Lung; Lipid Peroxidation; Antioxidants; Superoxide Dismutase; Oxidative Stress; Catalase; Phosphodiesterase Inhibitors; Nitric Oxide; Peroxidase; Lung Injury; Phosphoric Diester Hydrolases
PubMed: 38830372
DOI: 10.1055/a-2314-1137 -
Iranian Journal of Basic Medical... 2024Paraquat (PQ), a potent environmental herbicide, is recognized for inducing irreparable toxic damage to biological systems. This study aimed to evaluate the...
Evaluation of the influence of N-acetylcysteine and broccoli extract on systemic paraquat poisoning: Implications for biochemical, physiological, and histopathological parameters in rats.
OBJECTIVES
Paraquat (PQ), a potent environmental herbicide, is recognized for inducing irreparable toxic damage to biological systems. This study aimed to evaluate the effectiveness of N-acetylcysteine (NAC) and broccoli extract, individually and in combination, in alleviating PQ poisoning in rats, leveraging the exceptional anti-oxidant, anti-inflammatory, and anti-apoptotic properties of broccoli.
MATERIALS AND METHODS
Seventy Wistar rats were categorized into seven groups: C (control, vehicle), PQ (paraquat at 40 mg/kg), BC (broccoli extract at 300 mg/kg), NC (N-acetylcysteine at the same dose of 300 mg/kg), and combined groups PQ+BC, PQ+NC, and NC+PQ+BC, all administered equivalent doses. After 42 days, blood samples were collected to evaluate liver and kidney parameters, proinflammatory biomarkers, caspase-3, and caspase-9. Lung tissues were excised, with one part preserved for hydroxyproline and oxidative stress parameter measurement and another sectioned and stained for histopathological analysis.
RESULTS
The PQ group exhibited the highest lung-to-body weight (LW/BW) ratio, while the PQ+BC+NC group demonstrated the lowest ratio. Results indicated an elevated lung hydroxyproline concentration and a significant reduction in anti-oxidant enzymes (catalase, glutathione peroxidase, superoxide dismutase, and total anti-oxidant capacity) (<0.001). The PQ+BC group showed modified malondialdehyde levels, reaching a peak in the PQ group. Additionally, a significant decrease in tumor necrosis factor, interleukin-1, caspase-3, and caspase-9 was observed in the PQ+BC+NC group (<0.01). Pulmonary edema, hyperemia, and severe hemorrhage observed in the PQ group were notably reduced in the PQ+BC+NC group.
CONCLUSION
The combination of active compounds from broccoli and NAC demonstrated significant systemic and pulmonary effects in mitigating PQ-induced toxicity.
PubMed: 38800031
DOI: 10.22038/IJBMS.2024.75258.16311 -
Environmental Pollution (Barking, Essex... Aug 2024Exposure to pesticide could contribute to neurodevelopmental and neurodegenerative disorders. Notably, research suggests that prenatal or early postnatal exposure to...
Exposure to pesticide could contribute to neurodevelopmental and neurodegenerative disorders. Notably, research suggests that prenatal or early postnatal exposure to paraquat (PQ), an herbicide, might trigger neurodevelopmental toxicity in neural stem cells (NSCs) via oxidative stress. However, the molecular mechanisms of PQ-induced perturbations in NSCs, particularly at the metabolite level, are not fully understood. Using a dose-response metabolomics approach, we examined metabolic changes in murine NSCs exposed to different PQ doses (0, 10, 20, 40 μM) for 24h. At 20 μM, PQ treatment led to significant metabolic alterations, highlighting unique toxic mechanisms. Metabolic perturbations, mainly affecting amino acid metabolism pathways (e.g., phenylalanine, tyrosine, arginine, tryptophan, and pyrimidine metabolism), were associated with oxidative stress, mitochondrial dysfunction, and cell cycle dysregulation. Dose-response models were used to identify potential biomarkers (e.g., Putrescine, L-arginine, ornithine, L-histidine, N-acetyl-L-phenylalanine, thymidine) reflecting early damage from low-dose PQ exposure. These biomarkers could be used as points of departure (PoD) for characterizing PQ exposure hazard in risk assessment. Our study offers insights into mechanisms and risk assessment related to PQ-induced neurotoxicity in NSCs.
Topics: Animals; Neural Stem Cells; Mice; Paraquat; Metabolomics; Biomarkers; Herbicides; Oxidative Stress; Risk Assessment; Dose-Response Relationship, Drug
PubMed: 38795820
DOI: 10.1016/j.envpol.2024.124211 -
Academic Forensic Pathology Jun 2024Paraquat (N, N-dimethyl-4,4-bipyridinium dichloride) is a nonselective, fast-acting, and contact chemical herbicide used extensively for weed control. It has high acute... (Review)
Review
BACKGROUND
Paraquat (N, N-dimethyl-4,4-bipyridinium dichloride) is a nonselective, fast-acting, and contact chemical herbicide used extensively for weed control. It has high acute oral toxicity, the ability to accumulate in the lungs, and a high potential for pulmonary fibrosis after its intoxication. The present systematic review focuses on evaluating diagnostic aspects of paraquat (PQ) in forensic toxicology.
METHODS
Evaluation of the literature according to the following criteria: only human studies published from February 1971 to March 2022 which are in English on the following databases: 1) Medline/PubMed/MeSH search words: ((Methyl viologen [Title/Abstract]) OR (paraquat [MeSH Terms])) AND (forensic [Title/Abstract]); 2) Scopus Keywords related to the study aim included forensic toxicology, paraquat, Methyl viologen; 3) Web of Science. Keywords related to the study aim included forensic toxicology, paraquat, and Methyl viologen.
RESULTS
Thirty full-text articles were included. The results of our review indicate plasma and urine are more used for identifying PQ, and liver, lung, and gastric fluid are important in postmortem cases. Preparation methods, including liquid-liquid extraction (LLE), solid-phase extraction, and acetonitrile-precipitated protein, are often required for removing interfering substances. Chromatographic methods, among other analytical techniques, are more sensitive, specific, and applicable.
CONCLUSION
Our review suggests that plasma, urine, and lungs should be prioritized in sampling. Solid-phase extraction has better recovery than LLE in many samples. Colorimetric methods are not used much today, and radioimmunoassay (RIA) has limited application despite its high sensitivity. Gas and liquid chromatography methods appear to offer the best approach for the analysis of PQ.
PubMed: 38778898
DOI: 10.1177/19253621231214008 -
Chemico-biological Interactions Jul 2024Acute lung injury is the leading cause of paraquat (PQ) poisoning-related mortality. The mechanism by which macrophages are involved in PQ-induced acute lung injury...
Acute lung injury is the leading cause of paraquat (PQ) poisoning-related mortality. The mechanism by which macrophages are involved in PQ-induced acute lung injury remains unclear. In recent years, the role of metabolic reprogramming in macrophage functional transformation has received significant attention. The current study aimed to identify the role of altered macrophage glucose metabolism and molecular mechanisms in PQ poisoning-induced acute lung injury. We established a model of acute lung injury in PQ-intoxicated mice via the intraperitoneal injection of PQ. PQ exposure induces macrophage M1 polarization and promotes the release of inflammatory factors, which causes the development of acute lung injury in mice. In vitro analysis revealed that PQ altered glucose metabolism, which could be reversed by siRNA transfection to silence the expression of HK1, a key enzyme in glucose metabolism. RNA sequencing revealed that the ERK/MAPK pathway was the crucial molecular mechanism of PQ pathogenesis. Further, U0126, an ERK inhibitor, could inhibit PQ-induced HK1 activation and macrophage M1 polarization. These findings provide novel insights into the previously unrecognized mechanism of ERK/MAPK-HK1 activation in PQ poisoning.
Topics: Animals; Acute Lung Injury; Paraquat; Mice; Glucose; Macrophages; Hexokinase; MAP Kinase Signaling System; Mice, Inbred C57BL; Male; Signal Transduction; RAW 264.7 Cells
PubMed: 38763349
DOI: 10.1016/j.cbi.2024.111062 -
Respiratory Research May 2024Paraquat (PQ) is a widely used herbicide and a common cause of poisoning that leads to pulmonary fibrosis with a high mortality rate. However, the underlying mechanisms...
Paraquat (PQ) is a widely used herbicide and a common cause of poisoning that leads to pulmonary fibrosis with a high mortality rate. However, the underlying mechanisms of PQ-induced pulmonary fibrosis and whether pulmonary epithelial cell senescence is involved in the process remain elusive. In this study, PQ-induced pulmonary epithelial cell senescence and Hippo-YAP/TAZ activation were observed in both C57BL/6 mice and human epithelial cells. PQ-induced senescent pulmonary epithelial cells promoted lung fibroblast transformation through secreting senescence-associated secretory phenotype (SASP) factors. Yap/Taz knockdown in mice lungs significantly decreased the expression of downstream profibrotic protein Ctgf and senescent markers p16 and p21, and alleviated PQ-induced pulmonary fibrosis. Interfering YAP/TAZ in senescent human pulmonary epithelial cells resulted in decreased expression of the anti-apoptosis protein survivin and elevated level of apoptosis. In conclusion, our findings reveal a novel mechanism by which the involvement of Hippo-YAP/TAZ activation in pulmonary epithelial cell senescence mediates the pathogenesis of PQ-induced pulmonary fibrosis, thereby offering novel insights and potential targets for the clinical management of PQ poisoning as well as providing the mechanistic insight of the involvement of Yap/Taz activation in cell senescence in pulmonary fibrosis and its related pulmonary disorders. The YIN YANG balance between cell senescence and apoptosis is important to maintain the homeostasis of the lung, the disruption of which will lead to disease.
Topics: Animals; Cellular Senescence; YAP-Signaling Proteins; Humans; Mice, Inbred C57BL; Mice; Pulmonary Fibrosis; Adaptor Proteins, Signal Transducing; Transcription Factors; Paraquat; Male; Transcriptional Coactivator with PDZ-Binding Motif Proteins; Epithelial Cells; Trans-Activators
PubMed: 38762455
DOI: 10.1186/s12931-024-02832-z -
Journal of Hazardous Materials Jul 2024Paraquat (PQ) exposure is strongly associated with neurotoxicity. However, research on the neurotoxicity mechanisms of PQ varies in terms of endpoints of toxic...
An approach based on a combination of toxicological experiments and in silico predictions to investigate the adverse outcome pathway (AOP) of paraquat neuro-immunotoxicity.
Paraquat (PQ) exposure is strongly associated with neurotoxicity. However, research on the neurotoxicity mechanisms of PQ varies in terms of endpoints of toxic assessment, resulting in a great challenge to understand the early neurotoxic effects of PQ. In this study, we developed an adverse outcome pathway (AOP) to investigate PQ-induced neuro-immunotoxicity from an immunological perspective, combining of traditional toxicology methods and computer simulations. In vivo, PQ can microstructurally lead to an early synaptic loss in the brain mice, which is a large degree regarded as a main reason for cognitive impairment to mice behavior. Both in vitro and in vivo demonstrated synapse loss is caused by excessive activation of the complement C1q/C3-CD11b pathway, which mediates microglial phagocytosis dysfunction. Additionally, the interaction between PQ and C1q was validated by molecular simulation docking. Our findings extend the AOP framework related to PQ neurotoxicity from a neuro-immunotoxic perspective, highlighting C1q activation as the initiating event for PQ-induced neuro-immunotoxicity. In addition, downstream complement cascades induce abnormal microglial phagocytosis, resulting in reduced synaptic density and subsequent non-motor dysfunction. These findings deepen our understanding of neurotoxicity and provide a theoretical basis for ecological risk assessment of PQ.
Topics: Paraquat; Animals; Complement C1q; Phagocytosis; Computer Simulation; Microglia; Adverse Outcome Pathways; Male; Neurotoxicity Syndromes; Mice; Brain; Herbicides; CD11b Antigen; Complement C3; Molecular Docking Simulation; Synapses; Mice, Inbred C57BL
PubMed: 38761765
DOI: 10.1016/j.jhazmat.2024.134607 -
The Science of the Total Environment Jul 2024Paraquat (PQ) is a broad-spectrum herbicide used worldwide and is a hazardous chemical to human health. Cumulative evidence strengthens the association between PQ...
Paraquat (PQ) is a broad-spectrum herbicide used worldwide and is a hazardous chemical to human health. Cumulative evidence strengthens the association between PQ exposure and the development of Parkinson's disease (PD). However, the underlying mechanism and effective interventions against PQ-induced neurotoxicity remain unclear. In this study, C57BL/6 J mice were treated with PQ (i.p., 10 mg/kg, twice a week) and melatonin (i.g., 20 mg/kg, twice a week) for 8 weeks. Results showed that PQ-induced motor deficits and midbrain dopaminergic neuronal damage in C57BL/6 J mice were protected by melatonin pretreatment. In isolated primary midbrain neurons and SK-N-SH cells, reduction of cell viability, elevation of total ROS levels, axonal mitochondrial transport defects and mitochondrial dysfunction caused by PQ were attenuated by melatonin. After screening of expression of main motors driving axonal mitochondrial transport, data showed that PQ-decreased KIF5A expression in mice midbrain and in SK-N-SH cell was antagonized by melatonin. Using the in vitro KIF5A-overexpression model, it was found that KIF5A overexpression inhibited PQ-caused neurotoxicity and mitochondrial dysfunction in SK-N-SH cells. In addition, application of MTNR1B (MT2) receptor antagonist, 4-P-PDOT, significantly counteracted the protection of melatonin against PQ-induced neurotoxicity. Further, Kif5a-knockdown diminished melatonin-induced alleviation of motor deficits and neuronal damage against PQ in C57BL/6 J mice. The present study establishes a causal link between environmental neurotoxicants exposure and PD etiology and provides effective interventive targets in the pathogenesis of PD.
Topics: Paraquat; Animals; Melatonin; Mice; Mesencephalon; Mice, Inbred C57BL; Kinesins; Mitochondria; Herbicides; Neurons; Dopaminergic Neurons; Axonal Transport
PubMed: 38750743
DOI: 10.1016/j.scitotenv.2024.173119 -
Indian Journal of Critical Care... May 2024Patients with paraquat poisoning (PP) have a mortality rate comparable to that of advanced malignancies, yet palliative care is seldom considered in these patients. This...
BACKGROUND
Patients with paraquat poisoning (PP) have a mortality rate comparable to that of advanced malignancies, yet palliative care is seldom considered in these patients. This audit aimed to identify triggers for early palliative care referral in critically ill patients with PP.
METHODS
Medical records of patients with PP were audited. Predictors of mortality within 48 hours of hospitalization and 24 hours of intensive care unit (ICU) admission were considered as triggers for palliative care referral.
RESULTS
Among 108 patients, 84 complete records were analyzed, and 53 out of 84 (63.1%) expired. Within 48 hours after hospitalization, the lowest oxygen partial pressure in arterial blood to a fraction of inspired oxygen [the ratio of partial pressure of oxygen in arterial blood (PaO) to the fraction of inspiratory oxygen concentration (FiO) (PaO/FiO)] was the independent predictor of mortality, cut-off ≤ 197; the area under the curve (AUC), 0.924; sensitivity, 97%; specificity, 78%; <0.001; and 95% confidence interval (CI): 0.878-0.978. Kaplan-Meier survival plot showed that the mean survival time of patients with the lowest PaO/FiO, ≤197, was 4.64 days vs 17.20 days with PaO/FiO >197 (log-rank < 0.001). Sequential organ failure assessment (SOFA) score within 24 hours of ICU admission had a cut-off ≥9; AUC, 0.980; < 0.001; 95% CI: 0.955-1.000; 91% sensitivity; and 90% specificity for mortality prediction. Out of the total of 84 patients with PP analyzed, there were 11 patients admitted to the high dependency units (13.1%) and 73 patients admitted to the ICU (86.9%). Out of the total of 84 patients of PP in whom data was analyzed, 53 (63.1%) patients required ventilator support. All the 53 patients who required ventilator support due to worsening hypoxemia, eventually expired.
CONCLUSION
The lowest PaO/FiO ≤ 197 within 48 hours of hospitalization, SOFA score ≥9 within 24 hours of ICU admission or need for mechanical ventilation are predictors of mortality in PP patients, who might benefit from early palliative care.
HOW TO CITE THIS ARTICLE
Rao S, Maddani SS, Chaudhuri S, Bhatt MT, Karanth S, Damani A, Utility of Clinical Variables for Deciding Palliative Care in Paraquat Poisoning: A Retrospective Study. Indian J Crit Care Med 2024;28(5):453-460.
PubMed: 38738203
DOI: 10.5005/jp-journals-10071-24708 -
The Journal of the Association of... Mar 2024Paraquat (1,1'-dimethyl-4,4'-dipyridylium) is a liquid herbicide, linked to both accidental and intentional ingestion, which can result in severe and frequently lethal...
Paraquat (1,1'-dimethyl-4,4'-dipyridylium) is a liquid herbicide, linked to both accidental and intentional ingestion, which can result in severe and frequently lethal poisoning. It has been known to cause injury to the lungs, kidneys, and liver. We retrospectively reviewed five cases over the last 4 years with a history of paraquat ingestion. The time duration between ingestion and high-resolution computed tomography (HRCT) was assessed. HRCT chest scan was variable, ranging from 4 to 18 days postexposure. The follow-up of the patients was also reviewed.
Topics: Humans; Paraquat; Herbicides; Tomography, X-Ray Computed; Retrospective Studies; Male; Adult; Female; Lung
PubMed: 38736128
DOI: 10.59556/japi.72.0415