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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 -
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 -
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 -
Neurobiology of Disease Jun 2024Idiopathic Parkinson's disease (PD) is epidemiologically linked with exposure to toxicants such as pesticides and solvents, which comprise a wide array of chemicals that...
Idiopathic Parkinson's disease (PD) is epidemiologically linked with exposure to toxicants such as pesticides and solvents, which comprise a wide array of chemicals that pollute our environment. While most are structurally distinct, a common cellular target for their toxicity is mitochondrial dysfunction, a key pathological trigger involved in the selective vulnerability of dopaminergic neurons. We and others have shown that environmental mitochondrial toxicants such as the pesticides rotenone and paraquat, and the organic solvent trichloroethylene (TCE) appear to be influenced by the protein LRRK2, a genetic risk factor for PD. As LRRK2 mediates vesicular trafficking and influences endolysosomal function, we postulated that LRRK2 kinase activity may inhibit the autophagic removal of toxicant damaged mitochondria, resulting in elevated oxidative stress. Conversely, we suspected that inhibition of LRRK2, which has been shown to be protective against dopaminergic neurodegeneration caused by mitochondrial toxicants, would reduce the intracellular production of reactive oxygen species (ROS) and prevent mitochondrial toxicity from inducing cell death. To do this, we tested in vitro if genetic or pharmacologic inhibition of LRRK2 (MLi2) protected against ROS caused by four toxicants associated with PD risk - rotenone, paraquat, TCE, and tetrachloroethylene (PERC). In parallel, we assessed if LRRK2 inhibition with MLi2 could protect against TCE-induced toxicity in vivo, in a follow up study from our observation that TCE elevated LRRK2 kinase activity in the nigrostriatal tract of rats prior to dopaminergic neurodegeneration. We found that LRRK2 inhibition blocked toxicant-induced ROS and promoted mitophagy in vitro, and protected against dopaminergic neurodegeneration, neuroinflammation, and mitochondrial damage caused by TCE in vivo. We also found that cells with the LRRK2 G2019S mutation displayed exacerbated levels of toxicant induced ROS, but this was ameliorated by LRRK2 inhibition with MLi2. Collectively, these data support a role for LRRK2 in toxicant-induced mitochondrial dysfunction linked to PD risk through oxidative stress and the autophagic removal of damaged mitochondria.
Topics: Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; Animals; Reactive Oxygen Species; Rats; Trichloroethylene; Mitochondria; Rotenone; Parkinson Disease; Paraquat; Dopaminergic Neurons; Oxidative Stress; Humans; Environmental Pollutants; Rats, Sprague-Dawley
PubMed: 38705492
DOI: 10.1016/j.nbd.2024.106522 -
The Science of the Total Environment Jun 2024Parkinson's disease (PD) is a neurodegenerative disorder and leading cause of death worldwide, whose pathogenesis has been linked to toxic environmental exposures. We... (Meta-Analysis)
Meta-Analysis Review
Parkinson's disease (PD) is a neurodegenerative disorder and leading cause of death worldwide, whose pathogenesis has been linked to toxic environmental exposures. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (i) to compile, and group by exposure setting (non-specified general; residential; occupational), environmental factors reported to modulate the risk of developing PD and (ii) to map and geospatially analyze global regions of both research activity and paucity. Among the broader environmental settings, occupational exposures had the highest average odds ratio value at 3.82, followed by general (non-specified or mixed) exposures at 3.07, and residential exposures at 2.36. Occupational exposure to industrial toxins was the highest ranked subset of exposures with an odds ratio of 10.74. Among the studies meeting the inclusion criteria, 75 % were conducted in Europe or the Western United States. The number of individuals partaking per study ranged from a high of 55,585 (Taiwan) to a low of 233 (Faroe Islands), with a mean of n = 14,462. The top three environmental factors associated with high odds ratios for increased risk of developing PD were (i) exposure to dyes (25.33), (ii) methylene chloride (16.5) and specifically in adult men (iii) consumption of fatty whale meat (10.57), which is known to harbor a broad spectrum of so called persistent, bioaccumulative, toxic (PBT) pollutants. Geospatially, the highest odds ratio values were identified in European countries, whereas notable data gaps were revealed for South America, Australia, Africa, and the majority of Asia with the exception of Taiwan. Whereas occupational exposures to industrial chemicals, such as harmful dyes and methylene chloride, ranked highest in risk values, available data suggest notable opportunities for reducing PD cases globally by limiting harmful environmental exposures to a spectrum of toxic chemicals, particularly via the food intake route. Thus, current efforts in improving environmental quality globally by limiting toxic emission may deliver the added benefit of helping to reign in PD. Agents of concern in this respect include pesticides (e.g., paraquat, demeton, monocrotophos), particulate matter associated with air pollution, and a spectrum of organic and inorganic neurotoxins including heavy metals.
Topics: Parkinson Disease; Humans; Environmental Exposure; Environmental Pollutants; Risk Factors; Occupational Exposure
PubMed: 38685425
DOI: 10.1016/j.scitotenv.2024.172838 -
ACS Omega Apr 2024Paraquat (PQ) poisoning poses a significant public health concern. Unfortunately, point-of-care testing (POCT) of PQ in biofluids remains challenging. This study...
Paraquat (PQ) poisoning poses a significant public health concern. Unfortunately, point-of-care testing (POCT) of PQ in biofluids remains challenging. This study developed a portable kit that enables swift and reliable identification and quantification of PQ in human urine and gastric juice. The approach employed the surface-enhanced Raman scattering (SERS) technique, leveraging gold-silver core-shell nanoparticles (Au@Ag NPs) as the substrate. The kit comprised a portable Raman spectrometer and three sealed tubes containing Au@Ag NPs colloid, KI solution, and MgSO solution. A discernible correlation was observed between signal intensity and the logarithmic concentration, spanning from 5 to 500 μg/L in urine and 10 μg/L to 1 mg/L in gastric juice. The detection limits, calculated from the characteristic peak at 1648 cm , were 1.36 and 4.05 μg/L in human urine and gastric juice, respectively. Notably, this POCT kit obviated the need for pretreatment procedures, and the detection process was accomplished within 1 min, yielding satisfactory recoveries. This expeditious time frame is crucial for clinical diagnosis and rescue operations. Compared to conventional methods, this kit demonstrated real-time determinations in nonlaboratory settings. The simplicity and practicality of this POCT assay suggest its significant potential as an innovative alternative for poisoning detection applications.
PubMed: 38680347
DOI: 10.1021/acsomega.4c01163 -
International Journal of Molecular... Apr 2024Here, we continued the investigation of anti-HSV-1 activity and neuroprotective potential of 14 polyphenolic compounds isolated from heartwood. We determined the...
Here, we continued the investigation of anti-HSV-1 activity and neuroprotective potential of 14 polyphenolic compounds isolated from heartwood. We determined the absolute configurations of asymmetric centers in scirpusin A () and maackiazin () as 7,8 and 1″,2″, respectively. We showed that dimeric stilbens maackin () and scirpusin A () possessed the highest anti-HSV-1 activity among polyphenols -. We also studied the effect of polyphenols and on the early stages of HSV-1 infection. Direct interaction with the virus (virucidal activity) was the main mechanism of the antiviral activity of these compounds. The neuroprotective potential of polyphenolic compounds from was studied using models of 6-hydroxydopamine (6-OHDA)-and paraquat (PQ)-induced neurotoxicity. A dimeric stilbene scirpusin A () and a flavonoid liquiritigenin () were shown to be the most active compounds among the tested polyphenols. These compounds significantly increased the viability of 6-OHDA-and PQ-treated Neuro-2a cells, elevated mitochondrial membrane potential and reduced the intracellular ROS level. We also found that scirpusin A (), liquiritigenin () and retusin () considerably increased the percentage of live Neuro-2a cells and decreased the number of early apoptotic cells. Scirpusin A () was the most promising compound possessing both anti-HSV-1 activity and neuroprotective potential.
Topics: Polyphenols; Oxidative Stress; Herpesvirus 1, Human; Neuroprotective Agents; Antiviral Agents; Neurons; Animals; Herpes Simplex; Mice; Reactive Oxygen Species; Membrane Potential, Mitochondrial; Plant Extracts; Humans; Cell Survival
PubMed: 38673729
DOI: 10.3390/ijms25084142 -
Biomedica : Revista Del Instituto... Mar 2024Paraquat®, or N,N′-dimethyl-4,4′-bipyridinium dichloride, is a bipyridyl compound used as a non-selective herbicide and desiccant that can cause acute poisoning...
Paraquat®, or N,N′-dimethyl-4,4′-bipyridinium dichloride, is a bipyridyl compound used as a non-selective herbicide and desiccant that can cause acute poisoning through all routes of exposure. There is no known antidote, and the available treatments are based on avoiding its absorption and timely removing it, in adults and children. We describe a case series of 14 pediatric patients from the department of Cauca, Colombia, with acute intoxication after oral intake of paraquat. Patients were referred to a medium-high complexity hospital in southwestern Colombia and treated according to an institutional protocol for acute paraquat poisoning. Acute paraquat poisoning after oral ingestion is associated with a high mortality rate, even with timely medical attention, as the compound has no known antidote and quickly reaches systemic concentrations for fulminant poisoning. Based on the available literature, our center has proposed a clinical protocol including early standard management, immunosuppressive and antioxidant treatments, and systemic removal techniques. This protocol suggests an adequate approach to acute paraquat poisoning in the pediatric population.
Topics: Humans; Paraquat; Child; Female; Male; Child, Preschool; Adolescent; Algorithms; Herbicides; Poisoning; Colombia; Acute Disease; Infant; Antioxidants; Clinical Protocols; Antidotes
PubMed: 38648344
DOI: 10.7705/biomedica.7024 -
Frontiers in Microbiology 2024Defenses against oxidative damage to cell components are essential for survival of bacterial pathogens during infection, and here we have uncovered that the DmsABC...
Defenses against oxidative damage to cell components are essential for survival of bacterial pathogens during infection, and here we have uncovered that the DmsABC S-/N-oxide reductase is essential for virulence and in-host survival of the human-adapted pathogen, . In several different infection models, Δ strains showed reduced immunogenicity as well as lower levels of survival in contact with host cells. Expression of DmsABC was induced in the presence of hypochlorite and paraquat, closely linking this enzyme to defense against host-produced antimicrobials. In addition to methionine sulfoxide, DmsABC converted nicotinamide- and pyrimidine-N-oxide, precursors of NAD and pyrimidine for which is an auxotroph, at physiologically relevant concentrations, suggesting that these compounds could be natural substrates for DmsABC. Our data show that DmsABC forms part of a novel, periplasmic system for defense against host-induced S- and N-oxide stress that also comprises the functionally related MtsZ S-oxide reductase and the MsrAB peptide methionine sulfoxide reductase. All three enzymes are induced following exposure of the bacteria to hypochlorite. MsrAB is required for physical resistance to HOCl and protein repair. In contrast, DmsABC was required for intracellular colonization of host cells and, together with MtsZ, contributed to resistance to N-Chlorotaurine. Our work expands and redefines the physiological role of DmsABC and highlights the importance of different types of S-oxide reductases for bacterial virulence.
PubMed: 38638903
DOI: 10.3389/fmicb.2024.1359513 -
Iranian Journal of Basic Medical... 2024The effects of , safranal, and pioglitazone on aerosolized paraquat (PQ)-induced systemic changes were examined.
OBJECTIVES
The effects of , safranal, and pioglitazone on aerosolized paraquat (PQ)-induced systemic changes were examined.
MATERIALS AND METHODS
Control (Ctrl) and PQ groups of rats were exposed to saline or PQ (27 and 54 mg/m3, PQ-L and PQ-H) aerosols eight times on alternate days. Nine PQ-H groups were treated with dexamethasone (0.03 mg/kg/day, Dexa), two doses of extract (20 and 80 mg/kg/day, CS-L and CS-H), safranal (0.8 and 3.2 mg/kg/day, Saf-L and Saf-H), pioglitazone (5 and 10 mg/kg/day, Pio-L and Pio-H), and the combination of low dose of the pioglitazone and extract or safranal (Pio + CS and Pio + Saf) after the end of PQ exposure.
RESULTS
Interferon-gamma (INF-γ), interleukin 10 (IL-10), superoxide dismutase (SOD), catalase (CAT), and thiol serum levels were reduced, but tumor necrosis factor (TNF-α), malondialdehyde (MDA), and total and differential WBC were increased in both PQ groups (<0.05 to <0.001). All measured variables were improved in all treated groups (<0.05 to <0.001). The effects of high dose of C. sativus and safranal on measured parameters were higher than dexamethasone (<0.05 to <0.001). The effects of Pio + CS and Pio + Saf treatment on most variables were significantly higher than three agents alone (<0.05 to <0.001).
CONCLUSION
and safranal improved inhaled PQ-induced systemic inflammation and oxidative stress similar to those of dexamethasone and showed synergic effects with pioglitazone suggesting the possible PPARγ receptor-mediated effects of the plant and its constituent.
PubMed: 38629099
DOI: 10.22038/IJBMS.2024.72996.15867