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Toxicology Reports Dec 2023Paraquat poisoning is one of the leading causes of fatal poisoning in many parts of the world, especially in agricultural countries. Its high toxicity even in small...
BACKGROUND
Paraquat poisoning is one of the leading causes of fatal poisoning in many parts of the world, especially in agricultural countries. Its high toxicity even in small amounts causes rapid damage to multiple organs, especially the kidneys, lungs, and liver, mainly through free radical-mediated injury. As no specific antidote is yet available, early diagnosis and the importance of supportive therapy are critical parts of management. Some evidence suggests a survival benefit from using immunosuppressive drugs.
CASE REPORT
This case presentation concerns a 15-year-old boy from a village with a history of herbicide poisoning, later confirmed to be paraquat. Despite supportive therapy her condition continued to deteriorate with features of kidney and lung damage. The patient was then treated with methylprednisolone 500 mg daily for 5 days, along with other supportive care, and has made a remarkable recovery.
CONCLUSIONS
High efficacy as an herbicide, availability and low cost make paraquat an easy-to-encounter poison for suicidal or accidental use. Its high fatality calls for urgent and effective strategies to save lives. Methylprednisolone may play a role in its treatment.
PubMed: 37868809
DOI: 10.1016/j.toxrep.2023.10.008 -
Anais Da Academia Brasileira de Ciencias 2024Paraquat (1,1'-dimethyl-4,4'-bipyridyl dichloride) is an herbicide widely used worldwide and officially banned in Brazil in 2020. Kidney lesions frequently occur,...
Paraquat (1,1'-dimethyl-4,4'-bipyridyl dichloride) is an herbicide widely used worldwide and officially banned in Brazil in 2020. Kidney lesions frequently occur, leading to acute kidney injury (AKI) due to exacerbated reactive O2 species (ROS) production. However, the consequences of ROS exposure on ionic transport and the regulator local renin-angiotensin-aldosterone system (RAAS) still need to be elucidated at a molecular level. This study evaluated how ROS acutely influences Na+-transporting ATPases and the renal RAAS. Adult male Wistar rats received paraquat (20 mg/kg; ip). After 24 h, we observed body weight loss and elevation of urinary flow and serum creatinine. In the renal cortex, paraquat increased ROS levels, NADPH oxidase and (Na++K+)ATPase activities, angiotensin II-type 1 receptors, tumor necrosis factor-α (TNF-α), and interleukin-6. In the medulla, paraquat increased ROS levels and NADPH oxidase activity but inhibited (Na++K+)ATPase. Paraquat induced opposite effects on the ouabain-resistant Na+-ATPase in the cortex (decrease) and medulla (increase). These alterations, except for increased serum creatinine and renal levels of TNF-α and interleukin-6, were prevented by 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (tempol; 1 mmol/L in drinking water), a stable antioxidant. In summary, after paraquat poisoning, ROS production culminated with impaired medullary function, urinary fluid loss, and disruption of Na+-transporting ATPases and angiotensin II signaling.
Topics: Rats; Animals; Male; Renin-Angiotensin System; Reactive Oxygen Species; Paraquat; Angiotensin II; Creatinine; Interleukin-6; Tumor Necrosis Factor-alpha; Rats, Wistar; Kidney; Adenosine Triphosphatases; Sodium; NADPH Oxidases
PubMed: 38597493
DOI: 10.1590/0001-3765202420230971 -
Scientific Reports Nov 2023Paraquat (PQ) is a herbicide that has ability to induce testicular toxicity by producing reactive oxygen species (ROS). Sciadopitysin (SPS) is a promising flavonoid that...
Paraquat (PQ) is a herbicide that has ability to induce testicular toxicity by producing reactive oxygen species (ROS). Sciadopitysin (SPS) is a promising flavonoid that displays multiple pharmacological properties i.e., anti-inflammatory, anti-oxidant and anti-apoptotic. Therefore, the present study was designed to evaluate the mitigative role of SPS against PQ induced testicular toxicity in male rats. The experiment was performed on male albino rats (n = 48) that were divided into 4 groups. The group-1 was control group. Group-2 was administrated orally with PQ (5 mg/kg). Group-3 was administrated orally with PQ (5 mg/kg) and SPS (2 mg/kg). Group-4 was supplemented with SPS (2 mg/kg) through oral gavage. The experiment was conducted for 56 days. The exposure to PQ significantly lowered the activities of catalase (CAT), glutathione reductase (GSR), superoxide dismutase (SOD) as well as glutathione peroxidase (GPx). Whereas, a substantial increase was observed in dead sperms number, abnormalities in the tail, head as well as midpiece of sperms in PQ intoxicated rats. Moreover, a significant increase in the level of ROS and malondialdehyde (MDA) was noticed in PQ administrated group. Furthermore, steroidogenic enzymes expression was significantly decreased in PQ-intoxicated group, whereas the level of inflammatory markers was increased in PQ administrated rats. Besides, the expression of apoptotic markers was significantly escalated in PQ exposed rats, whereas the expression of anti-apoptotic markers was considerably reduced. A significant reduction in hormonal level was also noticed in the rats that were administrated with PQ. Moreover, the histopathological examination revealed that PQ significantly damaged the testicles. However, the supplementation of SPS with PQ significantly reduced the adverse effects of PQ in the testes of albino rats. Therefore, the current investigation demonstrated that SPS possesses a significant potential to avert PQ-induced testicular dysfunction due to its anti-apoptotic, androgenic, anti-oxidant and anti-inflammatory nature.
Topics: Rats; Male; Animals; Paraquat; Antioxidants; Testis; Reactive Oxygen Species; Anti-Inflammatory Agents; Oxidative Stress
PubMed: 37957289
DOI: 10.1038/s41598-023-46898-z -
PLoS Genetics Aug 2023Rapid depletion of cellular ATP can occur by oxidative stress induced by reactive oxygen species (ROS). Maintaining energy homeostasis requires the key molecular...
Rapid depletion of cellular ATP can occur by oxidative stress induced by reactive oxygen species (ROS). Maintaining energy homeostasis requires the key molecular components AMP-activated protein kinase (AMPK) and arginine kinase (AK), an invertebrate orthologue of the mammalian creatine kinase (CK). Here, we deciphered two independent and synergistic pathways of AMPK acting on AK by using the beetle Tribolium castaneum as a model system. First, AMPK acts on transcriptional factor forkhead box O (FOXO) leading to phosphorylation and nuclear translocation of the FOXO. The phospho-FOXO directly promotes the expression of AK upon oxidative stress. Concomitantly, AMPK directly phosphorylates the AK to switch the direction of enzymatic catalysis for rapid production of ATP from the phosphoarginine-arginine pool. Further in vitro assays revealed that Sf9 cells expressing phospho-deficient AK mutants displayed the lower ATP/ADP ratio and cell viability under paraquat-induced oxidative stress conditions when compared with Sf9 cells expressing wild-type AKs. Additionally, the AMPK-FOXO-CK pathway is also involved in the restoration of ATP homeostasis under oxidative stress in mammalian HEK293 cells. Overall, we provide evidence that two distinct AMPK-AK pathways, transcriptional and post-translational regulations, are coherent responders to acute oxidative stresses and distinguished from classical AMPK-mediated long-term metabolic adaptations to energy challenge.
Topics: Animals; Humans; AMP-Activated Protein Kinases; Arginine Kinase; HEK293 Cells; Oxidative Stress; Phosphorylation; Homeostasis; Adenosine Triphosphate; Mammals
PubMed: 37535699
DOI: 10.1371/journal.pgen.1010843 -
Metallomics : Integrated Biometal... May 2024Common features of neurodegenerative diseases are oxidative and inflammatory imbalances as well as the misfolding of proteins. An excess of free metal ions can be...
Common features of neurodegenerative diseases are oxidative and inflammatory imbalances as well as the misfolding of proteins. An excess of free metal ions can be pathological and contribute to cell death, but only copper and zinc strongly promote protein aggregation. Herein we demonstrate that the endogenous copper-binding tripeptide glycyl-l-histidyl-l-lysine (GHK) has the ability to bind to and reduce copper redox activity and to prevent copper- and zinc-induced cell death in vitro. In addition, GHK prevents copper- and zinc-induced bovine serum albumin aggregation and reverses aggregation through resolubilizing the protein. We further demonstrate the enhanced toxicity of copper during inflammation and the ability of GHK to attenuate this toxicity. Finally, we investigated the effects of copper on enhancing paraquat toxicity and report a protective effect of GHK. We therefore conclude that GHK has potential as a cytoprotective compound with regard to copper and zinc toxicity, with positive effects on protein solubility and aggregation that warrant further investigation in the treatment of neurodegenerative diseases.
Topics: Copper; Zinc; Protein Aggregates; Animals; Oligopeptides; Cell Death; Humans; Central Nervous System
PubMed: 38599632
DOI: 10.1093/mtomcs/mfae019 -
Current Research in Toxicology 2024Full treatment of the second most common neurodegenerative disorder, Parkinson's disease (PD), is still considered an unmet need. As the psychostimulants, amphetamine...
Full treatment of the second most common neurodegenerative disorder, Parkinson's disease (PD), is still considered an unmet need. As the psychostimulants, amphetamine (AMPH) and methylphenidate (MPH), were shown to be neuroprotective against stroke and other neuronal injury diseases, this study aimed to evaluate their neuroprotective potential against two dopaminergic neurotoxicants, 6-hydroxydopamine (6-OHDA) and paraquat (PQ), in differentiated human dopaminergic SH-SY5Y cells. Neither cytotoxicity nor mitochondrial membrane potential changes were seen following a 24-hour exposure to either therapeutic concentration of AMPH or MPH (0.001-10 μM). On the other hand, a 24-hour exposure to 6-OHDA (31.25-500 μM) or PQ (100-5000 μM) induced concentration-dependent mitochondrial dysfunction, assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, and lysosomal damage, evaluated by the neutral red uptake assay. The lethal concentrations 25 and 50 retrieved from the concentration-toxicity curves in the MTT assay were 99.9 µM and 133.6 µM for 6-OHDA, or 422 µM and 585.8 µM for PQ. Both toxicants caused mitochondrial membrane potential depolarization, but only 6-OHDA increased reactive oxygen species (ROS). Most importantly, PQ-induced toxicity was partially prevented by 1 μM of AMPH or MPH. Nonetheless, neither AMPH nor MPH could prevent 6-OHDA toxicity in this experimental model. According to these findings, AMPH and MPH may provide some neuroprotection against PQ-induced neurotoxicity, but further investigation is required to determine the exact mechanism underlying this protection.
PubMed: 38562456
DOI: 10.1016/j.crtox.2024.100165 -
JNMA; Journal of the Nepal Medical... Sep 2023Paraquat emerges as a formidable medical dilemma in Southeast Asia, its toxic effects attributed to the generation of free radicals and oxidative stress, with a specific...
UNLABELLED
Paraquat emerges as a formidable medical dilemma in Southeast Asia, its toxic effects attributed to the generation of free radicals and oxidative stress, with a specific predilection for diverse tissues, most notably the lungs. The scarcity of effective treatment modalities in resource-constrained settings magnifies the magnitude of the paraquat poisoning predicament. This report outlines the successful management of a 25-year-old man who ingested a lethal dose of paraquat. The patient presented solely with dysphagia devoid of accompanying symptoms, regardless of ingesting a fatal quantity of paraquat. The diagnosis was made based on history and a thorough clinical examination. Early, aggressive treatment with pulse therapy of steroids and antioxidants led to unexpected and quirky recovery. The case stresses the importance of prompt management and highlights the need for more research and public education to prevent future cases.
KEYWORDS
antioxidants; case reports; corrosive; paraquat; steroids.
Topics: Male; Humans; Adult; Paraquat; Lung; Treatment Outcome; Steroids; Poisoning
PubMed: 38289798
DOI: 10.31729/jnma.8263 -
Avicenna Journal of Phytomedicine 2023Paraquat (PQ) is a highly toxic herbicide that causes pulmonary fibrosis (PF), and no specific antidote is available against it. L. is a plant that exhibits antioxidant...
OBJECTIVE
Paraquat (PQ) is a highly toxic herbicide that causes pulmonary fibrosis (PF), and no specific antidote is available against it. L. is a plant that exhibits antioxidant and anti-inflammatory activities. The present study evaluates the preventive and therapeutic effects of extract (TPE) against PQ-induced lung fibrosis in rats.
MATERIALS AND METHODS
We divided rats into five groups of eight. Groups one and two received saline and PQ (20 mg/kg, i.p.), respectively. Groups three to five were treated with TPE (50, 100, and 200 mg/kg, by gavage) started one week before PQ administration and lasted three weeks after PQ administration.
RESULTS
Our findings showed that PQ significantly increased lung malondialdehyde, nitric oxide, hydroxyproline, lung index, Ashcroft score, red blood cells accumulation, and inflammatory cell infiltration. Moreover, PQ decreased catalase and glutathione peroxidase activities and glutathione content. The results of hematoxylin-eosin and Masson's trichrome staining indicated that PQ destroyed lung parenchyma and developed PF (p<0.05 to p<0.001). Gavage with TPE significantly improved biochemical and histological abnormalities induced by PQ in rats (p<0.05 to p<0.001).
CONCLUSION
The current survey indicated that treatment with TPE could reduce and reverse PQ-induced PF, which may be due to the phenolic compounds present in TPE.
PubMed: 38089422
DOI: 10.22038/AJP.2023.22121 -
Antioxidants (Basel, Switzerland) Jan 2024In this study, we examined the metabolic and gut microbiome responses to paraquat (PQ) in male Wistar rats, focusing on oxidative stress effects. Rats received a single...
In this study, we examined the metabolic and gut microbiome responses to paraquat (PQ) in male Wistar rats, focusing on oxidative stress effects. Rats received a single intraperitoneal injection of PQ at 15 and 30 mg/kg, and various oxidative stress parameters (i.e., MDA, SOD, ROS, 8-isoprostanes) were assessed after three days. To explore the omic profile, GC-qTOF and UHPLC-qTOF were performed to assess the plasma metabolome; H-NMR was used to assess the urine metabolome; and shotgun metagenomics sequencing was performed to study the gut microbiome. Our results revealed reductions in body weight and tissue changes, particularly in the liver, were observed, suggesting a systemic effect of PQ. Elevated lipid peroxidation and reactive oxygen species levels in the liver and plasma indicated the induction of oxidative stress. Metabolic profiling revealed changes in the tricarboxylic acid cycle, accumulation of ketone body, and altered levels of key metabolites, such as 3-hydroxybutyric acid and serine, suggesting intricate links between energy metabolism and redox reactions. Plasma metabolomic analysis revealed alterations in mitochondrial metabolism, nicotinamide metabolism, and tryptophan degradation. The gut microbiome showed shifts, with higher PQ doses influencing microbial populations (e.g., and ) and metagenomic functions (pyruvate metabolism, fermentation, nucleotide and amino acid biosynthesis). Overall, this study provides comprehensive insights into the complex interplay between PQ exposure, metabolic responses, and gut microbiome dynamics. These findings enhance our understanding of the mechanisms behind oxidative stress-induced metabolic alterations and underscore the connections between xenobiotic exposure, gut microbiota, and host metabolism.
PubMed: 38247491
DOI: 10.3390/antiox13010067 -
Frontiers in Neuroscience 2023Paraquat (1,1'-dimethyl-4-4'-bipyridinium dichloride) exposure is well-established as a neurotoxic agent capable of causing neurological deficits in offspring. This...
BACKGROUND
Paraquat (1,1'-dimethyl-4-4'-bipyridinium dichloride) exposure is well-established as a neurotoxic agent capable of causing neurological deficits in offspring. This study aimed to investigate therapeutic effects of L. aqueous extract (AU) against paraquat (PQ) exposure.
METHODS
For that the phytoconstituents of AU was determined by LC/MS, and then its antioxidant potential was assessed by DPPH and ABTS assays. The assessment included its impact on cell viability and mitochondrial metabolism using N27 dopaminergic cells. Additionally, we evaluated the effects of prenatal PQ exposure on motor coordination, dopamine levels, trace element levels, and total antioxidant capacity (TAC) in rat progeny.
RESULTS
The phytochemical profile of AU extract revealed the presence of 35 compounds, primarily phenolic and organic acids, and flavonoids. This accounted for its strong antioxidant activities against DPPH and ABTS radicals, surpassing the activities of vitamin C. Our findings demonstrated that AU effectively inhibited PQ-induced loss of N27 rat dopaminergic neural cells and significantly enhanced their mitochondrial respiration. Furthermore, daily post-treatment with AU during the 21 days of the rat's pregnancy alleviated PQ-induced motor deficits and akinesia in rat progeny. These effects inhibited dopamine depletion and reduced iron levels in the striatal tissues. The observed outcomes appeared to be mediated by the robust antioxidant activity of AU, effectively counteracting the PQ-induced decrease in TAC in the blood plasma of rat progeny. These effects could be attributed to the bioactive compounds present in AU, including phenolic acids such as gallic acid and flavonoids such as quercetin, rutin, apigenin, glucuronide, and kaempferol, all known for their potent antioxidant capacity.
DISCUSSION
In conclusion, this preclinical study provided the first evidence of the therapeutic potential of AU extract against PQ-induced neurotoxicity. These findings emphasize the need for further exploration of the clinical applicability of AU in mitigating neurotoxin-induced brain damage.
PubMed: 37901424
DOI: 10.3389/fnins.2023.1244603