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Antioxidants (Basel, Switzerland) Nov 2023Oxidative stress is the major incentive for intestinal dysfunction in weaned piglets, which usually leads to growth retardation or even death. Silybin has caught...
Oxidative stress is the major incentive for intestinal dysfunction in weaned piglets, which usually leads to growth retardation or even death. Silybin has caught extensive attention due to its antioxidant properties. Herein, we investigated the effect of dietary silybin supplementation on growth performance and determined its protective effect on paraquat (PQ)-induced intestinal oxidative damage and microflora dysbiosis in weaned piglets. In trial 1, a total of one hundred twenty healthy weaned piglets were randomly assigned into five treatments with six replicate pens per treatment and four piglets per pen, where they were fed basal diets supplemented with silybin at 0, 50, 100, 200, or 400 mg/kg for 42 days. In trial 2, a total of 24 piglets were randomly allocated to two dietary treatments with 12 replicates per treatment and 1 piglet per pen: a basal diet or adding 400 mg/kg silybin to a basal diet. One-half piglets in each treatment were given an intraperitoneal injection of paraquat (4 mg/kg of body weight) or sterile saline on day 18. All piglets were euthanized on day 21 for sample collection. The results showed that dietary supplementation with 400 mg/kg silybin resulted in a lower feed conversion ratio, diarrhea incidence, and greater antioxidant capacity in weaned piglets. Dietary silybin enhanced intestinal antioxidant capacity and mitochondrial function in oxidative stress piglets induced by PQ. Silybin inhibited mitochondria-associated endogenous apoptotic procedures and then improved the intestinal barrier function and morphology of PQ-challenged piglets. Moreover, silybin improved intestinal microbiota dysbiosis induced by the PQ challenge by enriching short-chain fatty-acid-producing bacteria, which augmented the production of acetate and propionate. Collectively, these findings indicated that dietary silybin supplementation linearly decreased feed conversion ratio and reduced diarrhea incidence in normal conditions, and effectively alleviated oxidative stress-induced mitochondrial dysfunction, intestinal damage, and microflora dysbiosis in weaned piglets.
PubMed: 38001828
DOI: 10.3390/antiox12111975 -
Scientific Reports Dec 2023Salmonella encounters but survives host inflammatory response. To defend host-generated oxidants, Salmonella encodes primary antioxidants and protein repair enzymes....
Salmonella encounters but survives host inflammatory response. To defend host-generated oxidants, Salmonella encodes primary antioxidants and protein repair enzymes. Methionine (Met) residues are highly prone to oxidation and convert into methionine sulfoxide (Met-SO) which compromises protein functions and subsequently cellular survival. However, by reducing Met-SO to Met, methionine sulfoxide reductases (Msrs) enhance cellular survival under stress conditions. Salmonella encodes five Msrs which are specific for particular Met-SO (free/protein bound), and 'R'/'S' types. Earlier studies assessed the effect of deletions of one or two msrs on the stress physiology of S. Typhimurium. We generated a pan msr gene deletion (Δ5msr) strain in S. Typhimurium. The Δ5msr mutant strain shows an initial lag in in vitro growth. However, the Δ5msr mutant strain depicts very high sensitivity (p < 0.0001) to hypochlorous acid (HOCl), chloramine T (ChT) and superoxide-generating oxidant paraquat. Further, the Δ5msr mutant strain shows high levels of malondialdehyde (MDA), protein carbonyls, and protein aggregation. On the other side, the Δ5msr mutant strain exhibits lower levels of free amines. Further, the Δ5msr mutant strain is highly susceptible to neutrophils and shows defective fitness in the spleen and liver of mice. The results of the current study suggest that the deletions of all msrs render S. Typhimurium highly prone to oxidative stress and attenuate its virulence.
Topics: Animals; Mice; Antioxidants; Methionine Sulfoxide Reductases; Oxidants; Oxidative Stress; Salmonella typhimurium; Virulence
PubMed: 38071209
DOI: 10.1038/s41598-023-48734-w -
Emergency Medicine International 2023The chest computed tomography (CT) examination is an important clinical examination in the diagnosis and monitoring of paraquat- (PQ-) induced lung injury. The aim of...
OBJECTIVE
The chest computed tomography (CT) examination is an important clinical examination in the diagnosis and monitoring of paraquat- (PQ-) induced lung injury. The aim of this study was to explore the prognostic value of the average lung CT number acquired by quantitative CT techniques in patients with acute paraquat poisoning in the early stages of the disease.
METHODS
46 patients who suffered from acute PQ poisoning in the emergency department of the Nanjing Drum Tower Hospital from January 2015 to June 2020 were enrolled in the present study. The patients were divided into survival group ( = 21) and nonsurvival group ( = 25). Clinical data were collected from subjects who met the inclusion criteria, including general information, personal disease history, and laboratory test indicators. The average lung CT numbers of each patient were obtained by quantitative CT techniques. Receiver operating characteristic (ROC) analysis was conducted to assess the prognostic value of average lung CT number in patients with acute paraquat poisoning.
RESULTS
The average CT numbers of the middle-lung, lower-lung, and whole lung fields in the nonsurvival group were significantly higher than those of the survival group ( < 0.0001). However, the upper-lung field was not significantly different between the two groups ( = 0.7765). The AUCs of different levels ranged from 0.554 to 0.977, among which the lower-lung field presented the largest AUC of 0.977 (95% CI: 0.943∼1; cut-off value: -702Hu; sensitivity 96%; specificity, 90.5%; YI: 0.865), followed by the whole lung field 0.914 (95% CI: 0.830∼0.999; cut-off value: -727Hu; sensitivity 76%; specificity, 95.2%; YI: 0.712) and the middle-lung field 0.87 (95% CI: 0.768∼0.971; cut-off value: -779Hu; sensitivity 80%; specificity, 85.7%; YI: 0.657).
CONCLUSION
The present study indicated that the average lung CT number could be used to evaluate the relationship between the severity of PQ-induced lung injury and prognosis, especially in the lower-lung field. However, further research is needed to draw a clear conclusion.
PubMed: 37731548
DOI: 10.1155/2023/4443680 -
Toxicology Letters Oct 2023Including active renal excretion in physiologically based kinetic (PBK) models can improve their use in quantitative in vitro- in vivo extrapolation (QIVIVE) as a new...
Including active renal excretion in physiologically based kinetic (PBK) models can improve their use in quantitative in vitro- in vivo extrapolation (QIVIVE) as a new approach methodology (NAM) for predicting the acute toxicity of organic cation transporter 2 (OCT2) substrates like paraquat (PQ). To realise this NAM, kinetic parameters Vmax and Km for in vitro OCT2 transport of PQ were obtained from the literature. Appropriate scaling factors were applied to translate the in vitro Vmax to an in vivo Vmax. in vitro cytotoxicity data were defined in the rat RLE-6TN and L2 cell lines and the human A549 cell line. The developed PQ PBK model was used to apply reverse dosimetry for QIVIVE translating the in vitro cytotoxicity concentration-response curves to predicted in vivo toxicity dose-response curves after which the lower and upper bound benchmark dose (BMD) for 50% lethality (BMDL and BMDU) were derived by applying BMD analysis. Comparing the predictions to the in vivo reported LD values resulted in a conservative prediction for rat and a comparable prediction for human showing proof of principle on the inclusion of active renal excretion and prediction of PQ acute toxicity for the developed NAM.
Topics: Rats; Humans; Animals; Models, Biological; Paraquat; Organic Cation Transporter 2; Renal Elimination; Cell Line
PubMed: 37806368
DOI: 10.1016/j.toxlet.2023.10.001 -
Clinical and Experimental Emergency... Jan 2024Following the 2011 ban on paraquat sales, South Korea has witnessed a significant reduction in the mortality rate associated with acute pesticide poisoning....
Following the 2011 ban on paraquat sales, South Korea has witnessed a significant reduction in the mortality rate associated with acute pesticide poisoning. Traditionally, paraquat and diquat, alongside several highly toxic organophosphates, carbamates, and organochlorine insecticides, have been recognized as culprits in causing fatalities among patients with acute pesticide poisoning. However, despite global efforts to curtail the use of these highly toxic pesticides, certain pesticides still exhibit a level of lethality surpassing their established clinical toxicity profiles. Understanding the clinical progression of these pesticides is paramount for physicians and toxicologists, as it holds the potential to enhance patient prognoses in cases of acute poisoning. This review aims to address the persistence of such highly lethal pesticides, which continue to pose a grave threat to victims of acute poisoning.
PubMed: 38286498
DOI: 10.15441/ceem.23.167 -
BioRxiv : the Preprint Server For... Jun 2024Flavin-containing monooxygenases (FMOs) are a conserved family of xenobiotic enzymes upregulated in multiple longevity interventions, including nematode and mouse...
Flavin-containing monooxygenases (FMOs) are a conserved family of xenobiotic enzymes upregulated in multiple longevity interventions, including nematode and mouse models. Previous work supports that promotes longevity, stress resistance, and healthspan by rewiring endogenous metabolism. However, there are five FMOs and five mammalian FMOs, and it is not known whether promoting longevity and health benefits is a conserved role of this gene family. Here, we report that expression of promotes lifespan extension and paraquat stress resistance downstream of both dietary restriction and inhibition of mTOR. We find that overexpression of in just the hypodermis is sufficient for these benefits, and that this expression significantly modifies the transcriptome. By analyzing changes in gene expression, we find that genes related to calcium signaling are significantly altered downstream of expression. Highlighting the importance of calcium homeostasis in this pathway, overexpressing animals are sensitive to thapsigargin, an ER stressor that inhibits calcium flux from the cytosol to the ER lumen. This calcium/ interaction is solidified by data showing that modulating intracellular calcium with either small molecules or genetics can change expression of and/or interact with to affect lifespan and stress resistance. Further analysis supports a pathway where modulates calcium homeostasis downstream of activating transcription factor-6 ( ), whose knockdown induces and requires expression. Together, our data identify as a longevity- promoting gene whose actions interact with known longevity pathways and calcium homeostasis.
PubMed: 38915593
DOI: 10.1101/2024.05.17.594584 -
Scientific Reports Jan 2024This study aimed to develop and validate a predictive model to determine the risk of in-hospital mortality in patients with acute paraquat poisoning. This retrospective... (Observational Study)
Observational Study
This study aimed to develop and validate a predictive model to determine the risk of in-hospital mortality in patients with acute paraquat poisoning. This retrospective observational cohort study included 724 patients with acute paraquat poisoning whose clinical data were collected within 24 h of admission. The primary outcome was in-hospital mortality. Patients were randomly divided into training and validation cohorts (7/3 ratio). In the training cohort, the least absolute shrinkage and selection operator regression models were used for data dimension reduction and feature selection. Multivariate logistic regression was used to generate a predictive nomogram for in-hospital mortality. The prediction model was assessed for both the training and validation cohorts. In the training cohort, decreased level of consciousness (Glasgow Coma Scale score < 15), neutrophil-to-lymphocyte ratio, alanine aminotransferase, creatinine, carbon dioxide combining power, and paraquat plasma concentrations at admission were identified as independent predictors of in-hospital mortality in patients with acute paraquat poisoning. The calibration curves, decision curve analysis, and clinical impact curves indicated that the model had a good predictive performance. It can be used on admission to the emergency department to predict mortality and facilitate early risk stratification and actionable measures in clinical practice after further external validation.
Topics: Humans; Hospital Mortality; Nomograms; Paraquat; Prognosis; Retrospective Studies
PubMed: 38238454
DOI: 10.1038/s41598-023-50722-z -
American Journal of Translational... 2023To investigate the effect of early, repeated hemoperfusion in conjunction with hemodialysis on the health status, blood-gas indices, and prognosis of patients with...
OBJECTIVE
To investigate the effect of early, repeated hemoperfusion in conjunction with hemodialysis on the health status, blood-gas indices, and prognosis of patients with paraquat (PQ) poisoning.
METHODS
In this retrospective study, clinical data of 149 PQ-poisoned patients treated at Xianyang First People's Hospital between January 2019 and January 2022 were analysed. Sixty-two patients who received conventional treatment coupled with early, repeated hemoperfusion were designated as the control group. The remaining 87 patients, who were subjected to additional hemodialysis on the basis of the control group, were designated in the experimental group. A comparison was made between the two groups regarding the changes in liver function, renal function, and blood-gas indices before and after the treatment. Three-month survival outcomes of both groups were analyzed using Cox regression, with survival curves drawn for different prognostic factors.
RESULTS
The experimental group exhibited significantly lower levels of indirect bilirubin (IBiL) and glutamic-pyruvic transaminase (ALT) after the treatment compared to the control group (all P < 0.05), as well as markedly lower levels of total bilirubin (TBil), direct bilirubin (DBil), glutamic-oxaloacetic transaminase (AST), alkaline phosphatase (ALP), urea nitrogen (BUN), and creatinine (Cr) (all P < 0.01). The experimental group also demonstrated significantly improved arterial partial pressure of oxygen (PaO) and PaO/inspired oxygen (FIO) ratios, along with reduced arterial carbon dioxide partial pressure (PaCO) after the treatment (all P < 0.05). Moreover, a significantly higher three-month survival rate was observed in the experimental group compared to the control group (P < 0.001). According to Cox regression analysis, blood purification mode, age, urine PQ concentration upon admission, the timing of initial gastric lavage and bowl cleanse, and the timing of initial blood purification were identified as independent factors affecting the patients' 90-day prognosis.
CONCLUSION
Early, repeated hemoperfusion coupled with hemodialysis significantly improves the blood-gas indices and liver and kidney function in patients with PQ poisoning, while also extending their short-term survival.
PubMed: 37854212
DOI: No ID Found -
Toxics Mar 2024Acute poisonings (AP) are a significant public health problem, accounting for a high number of emergency department visits and thousands of deaths worldwide. This study...
BACKGROUND
Acute poisonings (AP) are a significant public health problem, accounting for a high number of emergency department visits and thousands of deaths worldwide. This study aimed to assess the epidemiology of AP in an adult population admitted to Cayenne Hospital (French Guiana) and to investigate the clinical and sociodemographic characteristics.
METHODS
We conducted a monocentric retrospective study from January 2010 to December 2022, including patients over eighteen years of age who had been admitted to the emergency department of Cayenne Hospital for acute poisoning.
RESULTS
We included 425 patients. The median age was 34 years (IQR: 25-47). The sex ratio (M/F) was 0.52. A psychiatric disorder was found in 41.9% of patients. The Poisoning Severity Score (PSS) on admission was 1 or 2 for 84% of patients, and the mortality rate was 3.9%. The main involved toxicants were psychotropic drugs (43.1%), benzodiazepines (34.8%), and paracetamol (25.6%). The most lethal toxic was paraquat (5.2%). Intoxication was due to intentional self-poisoning in 84.2% of cases. Independent factors associated with severe poisoning (PSS 3 or 4) were chloroquine, neuroleptics, or paraquat poisoning; metabolic acidosis; and hyperglycemia (>5.5 mmol/L). The mortality rate was 3.9%, and the most involved toxic in death was paraquat.
CONCLUSION
This study shows the frequent and deadly use of paraquat in APs in French Guiana. Urgent attention should be given to establishing a toxicovigilance monitoring framework and an antipoison center in the region.
PubMed: 38535933
DOI: 10.3390/toxics12030200 -
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