Lung transplantation after paraquat poisoning in an adolescent: one case report and literature review / 器官移植

Objective To summarize the effect of the timing of lung transplantation and related treatment measures on clinical prognosis of patients with paraquat poisoning. Methods Clinical data of a patient with paraquat poisoning undergoing bilateral lung transplantation were retrospectively analyzed. Clinical manifestations, auxiliary examination, diagnosis and treatment of this patient were summarized and analyzed. Results A 17-year-old adolescent was admitted to hospital due to nausea, vomiting, cough and systemic fatigue after oral intake of 20-30 mL of 25% paraquat. After symptomatic support treatment, the oxygen saturation was not improved, and pulmonary fibrosis continued to progress. Therefore, sequential bilateral lung transplantation was performed under extracorporeal membrane oxygenation (ECMO). After postoperative rehabilitation and active prevention and treatment for postoperative complications, the patient was discharged at postoperative 50 d. Conclusions The timing of lung transplantation after paraquat poisoning may be selected when the liver and kidney function start to recover. Active and targeted prevention of potential pathogen infection in perioperative period and early rehabilitation training contribute to improving clinical prognosis of lung transplant recipients.

Intoxicação cutânea grave por Paraquat / Serious skin poisoning by Paraquat

O Paraquat é um herbicida não seletivo altamente tóxico, sendo responsável por altas taxas de letalidade acidentais ou provocadas, devido, principalmente, à insuficiência respiratória. Apesar de a intoxicação por via oral ser a principal e mais grave, o contato prolongado com a substância em uma grande área corporal pode gerar uma toxicidade similar e levar ao óbito ­ fato pouco elucidado na literatura. Este é o relato de caso de um homem de 22 anos, que foi admitido em um hospital devido a queixas de mal-estar, náuseas, febre, cefaleia, dor abdominal, diarreia, queimaduras e dispneia. A suspeita diagnóstica inicial foi de hantavirose, leptospirose, dengue e tromboembolismo pulmonar e, posteriormente, foi comprovado intoxicação exógena com agrotóxico por via inalatória e cutânea. Exames de imagem revelaram fibrose pulmonar difusa e ele também apresentou alterações renais, hepáticas e coagulatórias. Como não há antídoto específico, foi empregado tratamento sintomático e suportivo, com uso de carvão ativado, antibióticos, corticoides, antioxidantes e hemodiálise. No entanto, o paciente teve uma piora progressiva do quadro, vindo a óbito devido à síndrome da angústia respiratória aguda e fibrose pulmonar. O Paraquat, embora proibido no Brasil em 2020, continua sendo utilizado de forma ilegal. Além disso, seu substituto, o Diquat, possui toxicidade semelhante. Assim, é fundamental que os profissionais da saúde reconheçam o diagnóstico da intoxicação por tais substâncias e suas diferentes vias de exposição. Também são necessárias novas medidas de fiscalização das substâncias e maior investimento em educação em saúde para evitar exposições acidentais, assim como relatado (AU).

Paraquat is a highly toxic non-selective herbicide and is responsible for high accidental or provoked lethality rates, mainly due to respiratory failure. Although oral poisoning is the primary and most severe, prolonged contact with the substance in a large body area can lead to similar toxicity and death ­ a fact that is little elucidated in the literature. This is the case report of a 22-year-old man admitted to a hospital due to complaints of malaise, nausea, fever, headache, abdominal pain, diarrhea, burns and dyspnea. The initial diagnostic suspicion was hantaviruses, leptospirosis, dengue and pulmonary thromboembolism, and there was subsequently proven exogenous intoxication with pesticides by inhalation and cutaneous route. Imaging tests revealed diffuse pulmonary fibrosis and he also had renal, hepatic and coagulation alterations. As there is no specific antidote, symptomatic and supportive treatment was performed using activated charcoal, antibiotics, corticosteroids, antioxidants and hemodialysis. However, the patient had a progressive worsening of the condition and died due to acute respiratory distress syndrome and pulmonary fibrosis. Paraquat, although banned in Brazil in 2020, continues to be used illegally. In addition, its substitute, the Diquat, has similar toxicity. Thus, it is essential that health professionals recognize the diagnosis of intoxication by such substances and their different exposure routes. New control measures for these substances and greater investment in health education are also needed to prevent accidental exposure, as reported (AU).

Intoxicación por plaguicidas en autopsias medicolegales. Tegucigalpa 2014-2020 / Poisoning by pesticides in medicolegal autopsies. Tegucigalpa 2014- 2020

Justificación: Los plaguicidas han provocado un significativo problema de salud pública ya que han generado una importante carga a la mortalidad y a la morbilidad. Los suicidios con plaguicidas representan alrededor de un tercio de todos los suicidios en el mundo. Objetivo: Caracterizar las muertes relacionadas a plaguicidas, sometidas a autopsia médico legal en la Dirección de Medicina Forense de Tegucigalpa durante los años 2014- 2020. Metodología: Se consultó la base de datos digital la Dirección de Medicina Forense, encontrando 255 casos relacionados a muerte por plaguicidas de los que se seleccionaron 215 casos con expediente completo y disponible. Los cálculos estadísticos se realizaron con el programa PSPP. Resultados: Se encontraron 215 casos, el 58% eran hombres y el 42% mujeres, 54% eran solteros y 29% en unión libre. Sin escolaridad 11%, primaria incompleta 20%, primaria completa 15%, secundaria incompleta 12%, secundaria completa 10%. Respecto a la ocupación de los fallecidos, los oficios domésticos fue la más frecuente entre las mujeres y la agricultura entre los hombres. El 65% eran personas jóvenes menores de 40 años con una media de edad de 35 años (rango 8- 89a). La manera de muerte más frecuente fue suicida con el 71%. El plaguicida más utilizado como instrumento de muerte fue el fosfuro de aluminio (66%).Conclusión: La mayoría de las muertes por intoxicación con plaguicidas fueron suicidas; hombres jóvenes, menores de 40 años, solteros, con escolaridad que no sobrepasaba la secundaria; utilizaron las pastillas de fosfuro de aluminio como instrumento de autolesión. Se requiere estudiar más detalladamente el uso de tóxicos en general y de los plaguicidas en particular como instrumentos de autolesión y se evidencia la necesidad imperiosa de habilitar medidas de regulación para la comercialización y campañas de educación en la población para el uso y manejo adecuado...(AU)

Intoxicación fatal con paraquat por vía dérmica. Reporte de caso / Fatal paraquat poisoning by dermal exposure. Case report

Introducción: Por su alta letalidad el paraquat® es utilizado con fines suicidas, siendo la principal vía de uso, la oral; los casos por vía cutánea son escasos y raras veces son fatales. Este reporte presenta un caso de compromiso sistémico severo y muerte después de exposición dérmica a paraquat® . Resumen del caso: Paciente femenina de 47 años, soltera, ama de casa, de procedencia rural, con secundaria incompleta; e historia de aplicación de paraquat® en ulcera. A las 24h de aplicación presento fiebre, vómito y malestar general; al ingreso hospitalario presento además ictericia generalizada, insuficiencia renal aguda, insuficiencia respiratoria, deterioro progresivo de su estado de salud y muerte, por lo que fue remitida a autopsia médico legal. Los hallazgos de autopsia descartaron la ingesta oral y mostraron páncreas hemorrágico, riñones congestivos, hígado de tamaño aumentado (2550g) y hemorrágico, corazón aumentado de tamaño. Los estudios histopatológicos mostraron daño alveolar difuso, (membranas hialinas, edema y hemorragia); neumonía en pulmón y congestión visceral generalizada...(AU)

Role of JNK/AP-1 signaling pathway in paraquat-induced activation of NLRP3 inflammasome in microglia / 环境与职业医学

Background Paraquat (PQ) is one of the environmental factors that can cause sporadic Parkinson's disease (PD). Microglia-mediated neuroinflammation plays an important role in the occurrence and development of PD. Our previous studies have found that low doses of PQ can activate BV-2 microglia to the M1 phenotype and exert pro-inflammatory effects, but the associated mechanism is not clear yet. Objective To explore the role of c-Jun N-terminal kinase (JNK)/activator protein 1 (AP-1) signaling pathway in PQ-induced activation of the NOD-like receptor thermal protein domain associated protoin 3 (NLRP3) inflammasome in microglia. Methods An in vitro microglia model was established. The cells were treated with 0, 0.03, 0.06,and 0.12 μmol·L−1 PQ for 24 h, the whole cell protein was extracted. The relative expression levels of JNK, AP-1 constituent proteins (c-Jun, c-Fos), NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), caspasse-1 precursor (pro caspase-1), interleukin-18 (IL-18), and interleukin-1β (IL-1β) were evaluated by Western blotting, to observe the effects of PQ exposure on JNK/AP-1 signaling pathway and NLRP3 inflammasome. After the treatment of 20 μmol·L−1 JNK inhibitor SP600125, the above proteins were detected again, to explore the driving effect of JNK/AP-1 signaling pathway on NLRP3 inflammasome activation. Results After PQ exposure, the relative expression levels of key proteins of JNK, c-Jun, and c-Fos, NLRP3, ASC, and pro caspase-1 in the 0.06 μmol·L−1 PQ group and the 0.12 μmol·L−1 PQ group were higher than those in the 0 μmol·L−1 PQ group (P＜0.05), and the relative expression levels of IL-18 and IL-1β increased with higher exposure (P＜0.05). After the treatment of JNK inhibitor SP600125, the relative expression levels of key proteins of JNK/AP-1 signaling pathway (JNK, c-Jun, and c-Fos), NLRP3 inflammasome (NLRP3, ASC, and Pro caspase-1), and inflammatory factors (IL-18 and IL-1β) in the control group, the 20 μmol·L−1 SP600125 group, and the 20 μmol·L−1 SP600125+0.06 μmol·L−1 PQ group were lower than those in the 0.06 μmol·L−1 PQ group (P＜0.05). Conclusion PQ exposure can activate the JNK/AP-1 signaling pathway and subsequently drive the activation of NLRP3 inflammasome in BV-2 microglia to mediate neuroinflammatory responses..

Mutual promotion of mitochondrial fission and oxidative stress contributes to mitochondrial-DNA-mediated inflammation and epithelial-mesenchymal transition in paraquat-induced pulmonary fibrosis / 世界急诊医学杂志（英文）

@#BACKGROUND: Pulmonary fibrosis (PF) is one of the main causes of death in patients with paraquat (PQ) poisoning. This study aimed to evaluate the relationship between mitochondrial fission and oxidative stress in PQ-induced epithelial-mesenchymal transition (EMT) and PF. METHODS: C57BL/6 mice and MLE-12 cells were exposed to PQ to construct a PF model in vivo and in vitro. Histological changes in the lungs were examined by hematoxylin and eosin (H&E) staining. Mitochondrial morphology was detected by MitoTracker® Deep Red FM or transmission electron microscopy (TEM). Western blotting and immunofluorescence were used to determine the expression of protein. The migration ability of the cells was detected by the cell scratch test. Mitochondrial DNA (mtDNA) levels were assessed by real-time polymerase chain reaction (PCR). Enzyme-linked immunosorbent assay (ELISA) was applied to detect cytokine levels. Superoxide dismutase (SOD) activity and the levels of glutathione (GSH) and malondialdehyde (MDA) were detected by chemichromatometry. RESULTS: PQ exposure caused EMT and PF in vivo and in vitro. PQ destroyed mitochondrial structure and enhanced the expression of dynamin-related protein 1 (Drp1), which were accompanied by oxidative stress. Inhibiting mitochondrial fission using mitochondrial division inhibitor-1 (Mdivi-1), a selective inhibitor of Drp1, attenuated PQ-induced EMT and oxidative damage. Treatment with N-acetyl-L-cysteine (NAC), an antioxidant, reduced Drp1 expression, attenuated mitochondrial structure damage and inhibited PQ-induced EMT and PF. Both Mdivi-1 and NAC treatment markedly suppressed mtDNA release, the expression of Toll-like receptor 9 (TLR9) and phosphorylation (P)-NF-κB p65 as well as cytokines (interleukin 6 [IL-6], interleukin-1β [IL-1β], and tumor necrosis factor-α [TNF-α]) production. CONCLUSION: Mutual promotion of mitochondrial fission and oxidative stress contributes to EMT in PQ-induced PF, which is associated with the mtDNA/TLR9/NF-κB pathway.

Risk prediction of acute kidney injury in paraquat poisoning patients / 中华急诊医学杂志

Objective:To establish a risk prediction model of acute kidney injury in paraquat (PQ) poisoning patients.Methods:A retrospective observational cohort of adult patients with acute PQ poisoning between September 10, 2010 and January 16, 2020 from the Emergency Department of West China Hospital, Sichuan University were conducted. Data on demographics, clinical records, and laboratory results were collected from electronic medical record. The patients were divided into the AKI group and the non-AKI group according to whether AKI occurred during hospitalization. The patients were randomly divided into the training and validation groups (7:3). Multivariate logistic regression analysis was used to screen the independent risk factors of AKI and the nomogram was used to establish a prediction model. Receiver operating characteristic (ROC) curve and calibration curve were used to evaluate the differentiation and calibration of the prediction model. Decision curve analysis (DCA) was used to evaluate the clinical validity of the prediction model.Results:A total of 718 patients were included in this study. AKI occurred in 323 (45%) patients in hospital and 378 (52.6%) patients died. The mortality rate of the AKI group was higher than that of the non-AKI group (72.8% vs. 36.2%, P < 0.05). Multivariate logistic regression analysis showed that the time from poisoning to treatment ( OR=1.018, 95% CI:1.006-1.030), white blood cell count ( OR=1.128, 95% CI: 1.084-1.173), aspartate aminotransferase ( OR=1.017, 95% CI:1.006-1.027), cystatin C ( OR=516.753, 95% CI: 99.337-2688.172), and PQ concentration ( OR=1.064, 95% CI:1.044-1.085) in blood on admission were independent risk factors of AKI in patients with PQ poisoning ( P<0.01). The area under the ROC curve was 0.943 (95% CI: 0.923-0.962) in the training cohort, and the sensitivity and specificity were 82.4% and 93.6%, respectively. The calibration curve showed optimal agreement between prediction by nomogram and actual observation. Decision curve and clinical impact curve analysis indicated that the nomogram conferred high clinical net benefit. Conclusions:The time from poisoning to treatment, white blood cell count, aspartate aminotransferase, cystatin C, and PQ concentration in blood on admission were independent risk factors of AKI. The predictive model based on the above indicators has high sensitivity and specificity in evaluating AKI after PQ poisoning. Whether this prediction model can be applied to other PQ poisoning patients needs to be further expanded for verification.

Clinical characteristics of patients with paraquat mixed with diquat poisoning / 中华急诊医学杂志

Objective:To explore the clinical characteristics of patients with paraquat mixed with diquat poisoning.Methods:The clinical data of 145 patients with paraquat mixed with diquat poisoning admitted to the Department of Emergency of the First Affiliated Hospital of Wenzhou Medical University from January 20, 2016 to March 31, 2022 were retrospectively analyzed. According to the detection results of plasma toxicants in patients with poisoning, the patients were divided into the paraquat diquat mixed group (mixed group), paraquat group (PQ group) and diquat group (DQ group). The clinical indexes, organ dysfunction, different poisoning doses and prognosis of the three groups were compared. Patients in the mixed group were divided into the survival group and death group according to their 90-day survival, and the differences of each index between the two groups were compared. Kaplan-Meier survival analysis was conducted for each index. After Log-rank test, multivariate Cox regression was used to analyze the risk factors of death in the mixed group.Results:A total of 31 patients were included in the mixed group, 92 patients in the PQ group, and 22 patients in the DQ group. There were significant differences in age, toxic dose, number of organ dysfunction, PSS score and APACHE II score among the three groups ( P<0.05). The main injured organs of the mixed group were gastrointestinal tract, kidney, liver, lung and nervous system. The proportion of organ damage in the mixed group was higher than that in the PQ group and DQ group. The white blood cell count, neutrophil count, HB, creatinine, AST, lactic acid, PT and APTT were statistically significant among the three groups ( P<0.05). In the mixed group, patients taking oral administration of < 20 mL all survived; 8 patients taking oral administration of 20 -50 mL died; 11 patients took oral administration of 51-100 mL and 8 (72.7%) died; and 10 patients took oral administration of more than 100 mL and 9 patients (90%) died. In the mixed group, patients with the concentration of diquat > 5000 ng/mL died. Among 31 patients with mixed poisoning, 30 patients (96.78%) had significantly higher concentrations of diquat than paraquat. There were no significant differences in sex, age, time from poisoning to hospitalization, ingestion amount, lymphocyte count, Hb, BNU, CK, total bilirubin, PH, and PT between the survival group and the death group ( P>0.05). Multivariate Cox regression analysis showed that the ingestion amount, plasma PQ concentration at admission, plasma DQ concentration at admission, and lactic acid were independent risk factors for death ( P<0.05). Conclusions:Paraquat mixed with diquat can cause multiple organ function damage. The main damaged organs are gastrointestinal tract, kidney, liver, lung and nervous system. Compared with PQ or DQ poisoning, mixed poisoning has a higher incidence of organ damage, a more serious condition, and a higher mortality rate. Ingestion amount, plasma PQ concentration at admission, plasma DQ concentration at admission and lactic acid were independent factors influencing the prognosis of mixed poisoning.

Transcriptomic profiles of paraquat-induced Parkinson-like changes in mouse brains based on single-cell RNA sequencing / 环境与职业医学

Background Paraquat (PQ) is one of the most widely used herbicides in the world and a risk factor for Parkinson's disease (PD), but the mechanisms underlying PD are poorly understood. Single-cell RNA sequencing (scRNA-seq) technology can study cellular heterogeneity at genetic level, providing insights into the pathogenesis of PQ-induced PD. Objective To analyze the brain cell grouping of PQ-infected mice and the biological processes involved in the subpopulation of PD-like changes cells by scRNA-seq, and to provide clues for revealing potential mechanisms of PQ-induced PD-like changes in mouse brains. Methods Six male 6-week-old C57BL/6 mice were randomly divided into a control group and an experimental group, three mice in each group, and were intraperitoneally injected with 0 (saline) and 10.0 mg·kg−1 PD respectively, once every two days, for 10 consecutive injections for modeling. After infection, mouse brains were taken and scRNA-seq was performed. Cell segmentation was performed according to gene expression characteristics of different cell types, PD-related cell subsets were screened by bioinformatics tools, and gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), protein interaction network analysis, and transcription factor prediction were performed on their characteristic genes. Finally, GO and KEGG analyses were performed on the differential genes of PD-associated cell subsets between the PQ-treated group and the control group, and the biological processes in which these genes may participate were analyzed. Results The sequencing data met quality control standards, a total of 55779 cells were obtained, and all cell dimensionality reduction analysis results showed that they could be further divided into 37 clusters, including 5 major cell types. Based on the KEGG analysis of the top 20 characteristic genes of each subpopulation, the specifically expressed Cluster 33 subpopulation (dopaminergic neurons) was screened and found to be significantly associated with PD. The results of GO analysis showed that the biological function of this subpopulation mainly enriched neurotransmitter transport and regulation. The results of GSEA analysis showed that the tyrosine metabolic pathway and the ligand-receptor interaction pathway of neural activity in brain tissues were significantly enriched. The analysis of transcriptional regulatory networks showed that 39 transcription factors were expressed differently. The metabolic pathway of the dopamine neuronal subset, endocytosis, Ras-associated protein 1 (Rap1) signaling pathway, and mitogen-activated protein kinase (MAPK) signaling pathway were all affected by PQ exposure, according to further analysis of its effects on this subpopulation. The GO analysis showed that differential genes were involved in biological processes such as ion transport and synaptic assembly regulation, and were involved in the cellular component formation of cytoplasm and synapses. Conclusion This study has initially mapped the transcriptome of single cells in the mouse brain after PQ exposure, and screened out the specific expression of Cluster 33 subgroup (dopaminergic neurons), which is significantly correlated with PD, and its biological function changes may be one of the mechanisms of PD-like changes in the mouse brain induced by PQ.

Predictive value of serum lactate dehydrogenase on prognosis of patients with paraquat poisoning / 中华劳动卫生职业病杂志

Objective: To investigate the predictive value of serum lactate dehydrogenase (LDH) in the prognosis of patients with paraquat (PQ) poisoning, and to provide evidence for early prognosis assessment. Methods: In February 2022, 50 patients with PQ poisoning who completed serum LDH detection admitted to the Department of Emergency Medicine, the First Affiliated Hospital of Wenzhou Medical University from January 2012 to December 2021 were selected as the observation group, and 50 healthy physical examination personnel were randomly selected as the control group. Patients with PQ poisoning were divided into survival group and death group according to the prognosis, and the differences of blood routine routine, liver and kidney function and other indicators in the first admission between the two groups were compared. Multivariate logisitic regression model was established, ROC curve was drawn, and the influencing factors of prognosis of patients with PQ poisoning were analyzed. Results: Compared with the control group, the white blood cell count (WBC), total bilirubin (TBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), LDH, glucose (GLU) and creatinine (Cr) in observation group were significantly increased, while albumin (ALB) and total cholesterol (TC) were significantly decreased (P<0.05). Univariate analysis showed that WBC, elevated LDH (>247 U/L), TBil, ALT, AST and Cr were significantly different between PQ poisoning survival group and death group (P<0.05). Multivariate logisitic regression analysis showed that elevated serum LDH was an independent risk factor for the prognosis of PQ poisoning patients (OR=9.95, 95%CI: 1.34-73.82, P=0.025). The area under the ROC curve of LDH was 0.811 (95%CI: 0.692-0.930). When the cut-off value was 340 U/L, the sensitivity was 0.889 and the specificity was 0.719. Log-rank test showed that there was a statistically significant difference in survival rate between the normal LDH group and the elevated LDH group (P=0.001) . Conclusion: Serum LDH has a good predictive value in evaluating the prognosis of patients with PQ poisoning. Elevated LDH is a risk factor for poor prognosis of patients with PQ poisoning.

Effects of specimen preservation and transportation on blood paraquat concentration in rats / 中华劳动卫生职业病杂志

Objective: To investigate the effects of duration, temperature and shake on paraquat (PQ) concentration in the blood of PQ-exposed rats during the specinen preservation and transportation. Methods: In March 2021, 60 SD male rats of Specific Pathogen Free class were randomly divided into low-dose group (10 mg/kg PQ) and high-dose group (80 mg/kg PQ). Each group was divided into 5 subgroups (normal temperature group, cold storage group, 37 ℃ storage group, shaking on normal temperature group and shaking on 37 ℃ group), six rats in each subgroup. The rats were given intraperitoneal injection of PQ, 1 h after exposure, the blood samples were obtained by cardiac extraction. After different interventions, the concentrations of PQ were detected and compared before and after the intervention in each subgroup. Results: In the shaking on 37 ℃ group, the results of PQ concentrations in PQ-exposed rats were significantly lower than those before the intervention (P<0.05). In the other subgroups, the results were not significantly different compared with before intervention (P>0.05) . Conclusion: The concentration of PQ in the blood of rats exposed to PQ was decreased by shaking for 4 hours at 37 ℃.

Effect of pirfenidone on paraquat-induced pulmonary fibrosis in rats / 中华劳动卫生职业病杂志

Objective: To construct paraquat (PQ) poisoning rat model and to explore the effect of pirfenidone (PFD) on PQ-induced pulmonary fibrosis. Methods: In April 2017, male 6-8 week-old Wistar rats were selected, and PQ was administered intraperitoneally at one time. PFD was administered by gavage 2 hours after poisoning. The daily gavage doses were 100, 200 and 300 mg/kg, and the rats were divided into physiological saline group, PQ group, PQ+PFD 100 group, PQ+PFD 200 group, PQ+PFD 300 group, with 10 rats in each group at each observation time point. The pathological changes of lung tissue at different time points (the 1st, 3rd, 7th, 14th, 28th, 42nd and 56th days) after poisoning and the effect of PFD intervention with different dose on PQ-induced pulmonary fibrosis were observed. Pathological evaluation of lung tissue was performed by Ashcroft scale method. The PQ+PFD 200 group was selected to further explore the pathological changes of lung tissue, the contents of hydroxyproline and malondialdehyde in lung tissue were determined.And the tumor necrosis factor (TNF) -α, interleukin (IL) -6, transforming growth factor (TGF) -β1, fibroblast growth factor (FGF) -B, platelet-derived growth factor (PDGF) -AB, insulin-like growth factor (IGF) -1 and PQ concentrations in serum and lung tissue were determined. Results: On the 1st to 7th day after PQ exposure, rats developed lung inflammation, which was aggravated on the 7th to 14th day, and pulmonary fibrosis appeared on the 14th to 56th day. Compared with PQ group, the Ashcroft scores of lung fibrosis in PQ+PFD 200 group and PQ+PDF 300 group decreased significantly in 7th and 28th day (P<0.05), while the Ashcroft score of lung fibrosis in PQ+PFD 100 group had no significant difference (P>0.05). After PQ exposure, the content of hydroxyproline in lung tissue increased gradually and reached the peak value on the 28th day. Compared with the PQ group, the contents of hydroxyproline in the PQ+PFD 200 group decreased at the 7th, 14th and 28th day, and the contents of malondialdehyde decreased at the 3rd and 7th day, the differences were statistically significant (P<0.05). The levels of TNF-α, IL-6 in rat serum and lung tissue reached the peak value on the 7th day after PQ exposure, and the levels of TGF-β1, FGF-B and IGF-1 in rat serum and lung tissue reached the peak value on the 14th day after PQ exposure, and the level of PDGF-AB in rat serum and lung tissue reached the peak value on the 28th day after PQ exposure. Compared with PQ group, the level of serum IL-6 in PQ+PFD 200 group decreased significantly on the 7th day, and serum TGF-β1, FGF-B, PDGF-AB and IGF-1 on the 14th and 28th day were decreased significantly (P<0.05). The levels of TNF-α, IL-6 in lung tissue of rats in PQ+PFD 200 group on the 7th day decreased significantly, and the levels of TGF-β1, FGF-B and IGF-1 in lung tissue of rats on the 14th day were significantly decreased, and the level of PDGF-AB in lung tissue of rats on the 28th day were significantly decreased (P<0.05) . Conclusion: PFD partially alleviates the PQ-induced lung inflammation and fibrosis by inhibiting oxidative stress, reducing the levels of pro-inflammatory and pro-fibrotic cytokines in serum and lung tissue, but does not affect the concentrations of PQ in serum and lung tissue.

Effects of Nintedanib associated with Shenfu Injection on paraquat-induced lung injury in rats / 中华劳动卫生职业病杂志

Objective: To study the effects of Nintedanib associated with Shenfu Injection on lung injury induced by paraquat (PQ) intoxication. Methods: In September 2021, a total of 90 SD rats were divided into 5 groups in random, namely control group, PQ poisoning group, Shenfu Injection group, Nintedanib group and associated group, 18 rats in each group. Normal saline was given by gavage route to rats of control group, 20% PQ (80 mg/kg) was administered by gavage route to rats of other four groups. 6 hours after PQ gavage, Shenfu Injection group (12 ml/kg Shenfu Injection), Nintedanib group (60 mg/kg Nintedanib) and associated group (12 ml/kg Shenfu Injection and 60 mg/kg Nintedanib) were administered with medicine once a day. The levels of serum transforming growth factor beta1 (TGF-β1), interleukin-1 beta (IL-1β) were determined at 1, 3 and 7 d, respectively. The pathological changes of lung tissue, the ratio of wet weight and dry weight (W/D) of lung tissue, the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in lung tissue were observed and determined after 7 d. Western blot was used to analyse the expression levels of fibroblast growth factor receptor 1 (FGFR1), platelet derivation growth factor receptor alpha (PDGFRα), vascular endothelial growth factor receptor 2 (VEGFR2) in lung tissue after 7 d. Results: The levels of TGF-β1, IL-1β in all poisoning groups went up first and then went down. The levels of TGF-β1, IL-1β in associated group at 1, 3, 7 d were lower than that of PQ poisoning group, Shenfu Injection group and Nintedanib group at the same point (P<0.05). Pathological changes of lung tissue under the light microscopes showed that the degrees of hemorrhage, effusion and infiltration of inflammatory cells inside the alveolar space of Shenfu Injection group, Nintedanib group and associated group were milder than that of PQ poisoning group, and the midest in associated group. Compared with control group, the W/D of lung tissue was higher, the level of MDA in lung tissue was higher, while the level of SOD was lower, the expressions of FGFR1, PDGFRα and VEGFR2 in lung tissue were higher in PQ poisoning group (P<0.05). Compared with PQ poisoning group, Shenfu Injection group and Nintedanib group, the W/D of lung tissue was lower, the level of MDA in lung tissue was lower, while the level of SOD was higher, the expressions of FGFR1, PDGFRα and VEGFR2 in lung tissue were lower in associated group (P<0.05) . Conclusion: Nintedanib associated with Shenfu Injection can relieve lung injury of rats induced by PQ, which may be related to Nintedanib associated with Shenfu Injection can inhibit the activation of TGF-β1 and the expressions of FGFR1, PDGFRα, VEGFR2 in lung tissue of rats.

The risk prediction value of paraquat poisoning dose, urine protein and myocardial enzymes / 中华劳动卫生职业病杂志

Objective: To explore the value of paraquat (PQ) intake, urine protein and myocardial enzyme indexes in judging the prognosis of patients with acute PQ poisoning. Methods: From September to December 2021, all 201 patients with acute PQ poisoning admitted to Guangzhou Twelfth People's Hospital from January 2010 to December 2019 were selected as the research objects. Based on follow-up results 60 days after poisoning, the research objects were divided into survival group (n=78) and death group (n=123) . The differences in information about poisoning, treatment plan, PQ intake, urine protein, creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase between the two groups of patients were compared and analyzed. Logistic regression and Cox regression were used to analyze the correlation between poisoning outcome and PQ intake, urine protein and myocardial enzymes. ROC curve and principal component analysis were used to explore high-efficiency indicators for predicting the outcome of acute PQ poisoning. Results: The PQ intake[50 (20, 100) ml], urine protein (total rank 15570.50) , creatine kinase[ (336.36±261.96) U/L], creatine kinase isoenzyme[ (43.91±43.74) U/L], lactate dehydrogenase [ (346.01±196.50) U/L], α-hydroxybutyrate dehydrogenase content[ (271.23±11.92) U/L] of patients in the death group were all higher than the survival group[15 (10, 20) ml, 4730.50, (187.78±178.06) U/L, (18.88±15.50) U/L, (190.92±60.50) U/L, (152.60±48.34) U/L, respectively] (P<0.05) . The outcome of acute PQ poisoning was positively correlated with PQ intake, urine protein, creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase (P<0.05) . Multivariate logistic regression and multivariate Cox regression analysis showed that creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase and α-hydroxybutyrate dehydrogenase was positively correlated with the prognosis of patients with acute PQ poisoning (P<0.05) . ROC curve analysis and principal component analysis showed that the combined indexes of PQ intake, urine protein and myocardial enzymes had the highest efficacy and weight in judging the prognosis of patients (AUC=0.91, weight coefficient=0.19, sensitivity=0.76, specificity=0.89) . When the combined score was ≥4, the probability of accurately predicting the death of patients was as high as 91% (positive predictive value=0.91) . Conclusion: PQ intake, urine protein combined with creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase has high value in predicting the prognosis of patients with acute PQ poisoning.

Swertiamarin attenuates paraquat-induced pulmonary epithelial-like cell apoptosis via NOX4-mediated regulation of redox and mitochondrial function

Abstract The aim of the present study was to investigate the effect of swertiamarin (STM) in attenuating paraquat (PQ)-induced human lung alveolar epithelial-like cell (A549) apoptosis and the underlying mechanisms. A549 cells were pretreated with different concentrations of STM for 2 hr and then cultured with or without PQ (700 µM) for 24 hr. Cell survival was determined using the CCK8 assay. Morphological changes, MDA content, inflammatory factors, fibrogenesis parameters, apoptosis rates, redox status and mitochondrial membrane potential (MMP) were evaluated. The expression of several genes involved in the modulation of redox status was measured by Western blotting. Cell viability and MMP were decreased, but the apoptosis rate and DCFH oxidation were elevated by PQ exposure. STM pretreatment notably increased cell viability and MMP and reduced the apoptosis rate and DCFH oxidation. Furthermore, TLR4- NOX4 signaling was significantly inhibited by STM. The downregulation of NOX4 by siRNA exerted the same protective effects as STM. This study provides the first evidence that STM attenuates PQ-induced pulmonary epithelial-like cell apoptosis via NOX4-mediated regulation of redox and mitochondrial function

Clinical profile and outcome of paraquat poisoning at a tertiary care centre in North Karnataka, a retrospective observational study

Background: Paraquat is a herbicide commonly used for controlling weeds in India. The primary target organs for paraquat poisoning are the lungs and the kidneys. Acute cases of poisoning with paraquat are admitted to the hospital with various stages of acute kidney injury. Aim: To study the clinical presentation and outcome of paraquat poisoning in a tertiary care setting. Materials and Methods: A retrospective observational study was conducted at SDM College of Medical Sciences and Hospital, Dharwad. In this study we included the data of all patients admitted to the hospital with paraquat poisoning for a period of three-year and four months between January 2018 to April 2021. Results: A total of 12 participants were included in the final analysis. All the patients consumed paraquat with the suicidal intention only. The quantity of paraquat ingested was quite varied, ranging from as low as 5ml to as high as 200ml. Acute Kidney Injury (AKI) was diagnosed in 58.3% of patients. Among which three patients were in stage 1, one was in stage 2, and three were in stage 3. The mortality rate was 58.33%. The major cause of death for these patients was multiple organ dysfunction syndromes (71.42 %). Conclusion: Acute kidney injury is the major clinical outcome of paraquat poisoning other than lung injury. This may result in multiple organ dysfunction syndrome (MODS) and mortality. Paraquat poisoning is due to consumption with suicidal intent. Most of them were young. Early management with hemoperfusion may have a positive effect on reducing mortality.

Utilidad de la tomografía en la intoxicación por paraquat: reporte de caso / Serviceability of tomography in paraquat poisoning: a case report

Resumen El paraquat es un plaguicida del grupo de los herbicidas asociado a una gran morbimortalidad, luego de su ingesta con intención suicida. Dentro de las ayudas pronósticas, en el paciente intoxicado por esta sustancia, la literatura internacional considera la tomografía de tórax y sus hallazgos, sin embargo, en Colombia, no hay reportes a nivel nacional, ni inclusión de este parámetro dentro de las guías del Ministerio de Salud. Reportamos el caso de una paciente con diagnóstico tardío de intoxicación por paraquat, la tomografía de ingreso no indicó compromiso pulmonar así que se inició tratamiento y se obtuvo resultados favorables relacionados con la supervivencia de la paciente.

Abstract Paraquat is a pesticide from the group of herbicides associated with high morbidity and mortality after ingestion with suicidal intent. Within the prognostic aids, in the patient intoxicated by this substance, the international literature considers the chest tomography and its findings. However, in Colombia, there are no reports at the national level, nor is there any inclusion of this parameter within the guidelines of the Ministry of Health. We report the case of a patient with a late diagnosis of paraquat poisoning, admission tomography did not indicate pulmonary compromise, so treatment was started and favorable results related to the patient's survival were obtained.

Características sociodemográficas y clínicas relacionadas con la condición final de pacientes intoxicados por paraquat en un hospital del suroccidente de Colombia / Sociodemographic and clinical characteristics related to the final condition of patients intoxicated by paraquat in a hospital in southwestern Colombia

Introducción. El herbicida paraquat constituye la primera causa de decesos por intoxicaciones en distintos países. Objetivo. Relacionar las características sociodemográficas y clínicas con la condición final de pacientes intoxicados por paraquat atendidos en un hospital del suroccidente de Colombia. Materiales y métodos. En este estudio observacional, descriptivo, analítico, transversal y retrospectivo, se revisaron las historias clínicas de pacientes atendidos por intoxicación con paraquat en una institución de tercer nivel de complejidad en Pasto (Colombia) entre el 2013 y el 2018. Se recolectó la información sobre la condición final (vivo o fallecido) de cada paciente, así como los datos sociodemográficos, clínicos y de los exámenes paraclínicos. Se establecieron comparaciones por grupos y se diseñó un modelo de regresión logística binaria. Resultados. Se filtró la información de 299 registros y se analizaron finalmente 160 casos. Las características relacionadas con la condición final de los pacientes fueron el tiempo de estancia (OR=0,124; IC95% 0,03-0,6; p=0,009), la frecuencia cardiaca (OR=35,65; IC95% 1,44-884,78; p=0,029) y la creatinina inicial (OR=1,73; IC95% 1,23-2,44; p=0,002). Conclusiones. La proporción de la letalidad fue mayor entre los pacientes con estancia hospitalaria corta, taquicardia y elevación de la concentración sérica de creatinina al ingreso. Este reporte puede ser útil como fundamento de una escala de gravedad para detectar a los pacientes con resultados adversos en la fase temprana para que puedan recibir una intervención oportuna.

Introduction: Paraquat is an agrochemical that constitutes the first cause of death by poisoning in different countries. Objective: To relate sociodemographic and clinical characteristics with the final condition of patients intoxicated by paraquat in a hospital in southwestern Colombia. Materials and methods: This was an observational, descriptive, analytical, crosssectional, and retrospective study. We reviewed the medical records of patients diagnosed with paraquat poisoning at a level III hospital in Pasto, Colombia, from 2013 to 2018. We collected the data regarding their final condition (alive or deceased) and their sociodemographic, clinical, and paraclinical information. We established group comparisons and designed a binary logistic regression model. Results: We reviewed 299 records and, after the exclusion, we analyzed 160 cases. The characteristics related to the final condition of the patients were length of stay (OR = 0.124; 95% CI: 0.03-0.6; p = 0.009), heart rate (OR = 35.65; 95% CI: 1.44-884.78; p = 0.029), and initial creatinine (OR = 1.73; 95% CI: 1.23-2.44; p = 0.002). Conclusion: The proportion of case fatality was higher in patients with short hospital stay times and elevated heart rates and admission creatinine levels. This report may be useful as a rationale for the creation of a severity scale for the early detection of patients with adverse outcomes and their timely treatment.

Paraquat-induced lung fibrosis and multiorgan failure: A case report from North India

Paraquat is a herbicide which is widely used by agricultural communities worldwide. It is extremely toxic for humans and ingestion of as less as 30 mL of 20%–24% concentration is usually lethal. The lack of an effective antidote is a concern due to the fatal outcomes associated with ingestion of paraquat. Herein, we are presenting a case of fatal paraquat poisoning in a young male from a center in India. The clinical course was complicated by liver, renal, and lung injury. We also describe its mechanism of toxicity, clinical features, and newer strategies being tried for treatment.

The Comparative Effects of Vitamin E + C on the Chronic Toxicity of Paraquat in Albino Rats (Rattus norvegicus)

Paraquat is a highly toxic chemical used in weed control. Paraquat is known for its ability to generate reactive oxygen species that attack cells and membranes. Vitamin E is a group of vitamins which dissolves in fat and possess antioxidant properties which act as a defense to the cells against oxidative stress arising from reactive oxygen species, whereas Vitamin C is a water soluble vitamin and a very potent antioxidant which protects the cells of the body from free radicals. The study aim was to evaluate the ameliorative effects of a combination therapy of vitamin E and C on biochemical markers of paraquat induced male albino rats. 200 male albino rats with 0.2±0.02 kg mean weight were used. The 200 rats were divided into four main groups with 50 rats within a group. The groups were labeled A, B C and D. The “A” group was neutral; “B” group was induced with 0.02 g, “C” 0.06g, and “D” 0.06 g of paraquat per kg rat every two weeks for three months. The main groups further had subgroups. “A” group had “A0” and “AVEC” subgroups; “B” group had “B0” and “BVEC” subgroups; “C” group had “C0” and “CVEC” subgroups; “D” group had “D0” and “DVEC” subgroups. “A0”, “B0”, “C0” and “D0” subgroups were not administered with vitamin E + C therapy while “AVEC”, “BVEC”, “CVEC” and “DVEC” were treated orally with 500 mg of vitamin E weekly and 2000 mg/l of vit C medicated water for one month. After then, the rats were sacrificed, blood samples were collected and analyzed for the liver function; T. bilirubin, D. bilirubin, T. protein, albumin, and globulin. ANOVA intergroup comparison of A0, B0, C0 and D0 was statistically significant, p-value<0.05 except for globulin. Intergroup comparison of AVEC, BVEC, CVEC and DVEC was statistically significant, p-value<0.05 except for globulin. Intra-group comparison showed significant difference only in total bilirubin and conjugated bilirubin levels, p-value<0.05. This study therefore has shown that weekly treatment with Vit E + C in one month can treat liver toxicity in rats.