Paraquat Ingestion Research Articles

Paraquat – A mortal herbicide

Paraquat (1,1´-dimethyl-4,4´-dipyridylium) is a broad-spectrum liquid herbicide. It is associated with both intentional and accidental ingestion that leads to severe and often fatal toxicity. The clinical signs and symptoms of paraquat poisoning includes Gastrointestinal symptoms such as burns in the throat, difficulty in breathing, sore throat, abdominal pain and vomiting, including hematemesis, Electrolyte abnormalities, Low bold pressure, seizure, shock and coma. This is a case report of young male presented to IMCU with the history of more than 48hrs after the ingestion of paraquat.

Clinical and pathological profile of paraquat poisoning cases - A cross-sectional study in Odisha, India

Agriculture being the primary mode of occupation in Odisha leads to the rampant and widespread use of chemical pesticides and herbicides. Paraquat is a widely used herbicide. Ingestion of PQ irrespective of the quantity could be fatal with life-threatening effects on the gastrointestinal (GI) tract, kidney, liver, lungs, and other organs. Death is usually associated with respiratory insufficiency due to an oxidative insult to the Type-II alveolar epithelium with subsequent fibrosis.All cases of paraquat ingestion coming to AIIMS, Bhubaneswar casualty from July 2020 to November 2020 were studied for their clinical findings. The fatal cases were subjected to autopsy and findings noted.Men were most commonly involved. All of the patients had self-harm intent while consuming. The most common presenting symptoms were difficulty in swallowing, Respiratory system was most commonly affected. The cause of death was attributed to respiratory and multi-organ failure.Paraquat is widely marketed for its efficacy and low environmental toxicity. Lack of a specific antidote increases the fatality. The most common cause of death is respiratory failure. Paraquat causes renal failure by causing hypovolemia, circulatory failure, septicemia, and direct toxicity. The mainstay of treatment is supportive though the use of immune-suppressants has shown some positive results.

Thoracic radiographic features of fatal paraquat intoxication in eleven dogs

Background Paraquat (1,1-dimethyl-4,4-bipyridinium dichloride) is a toxic herbicide. Accidental ingestion of paraquat in animals and humans causes respiratory failure and death. Aim To describe the radiographic features of confirmed paraquat intoxication in a group of dogs and determines whether any identified features can facilitate this diagnosis. Methods Eleven dogs diagnosed with paraquat intoxication were selected from two institutions between November 2014 and August 2019 comprising five males (all intact) and six females (one intact and five spayed). The mean age was 3.9 ± 2.9 (SD) years and their mean weight was 11.6 ± 5.0 kg. The tentative diagnosis was confirmed through analysis of their urine samples using a colorimetric assay (paraquat concentation 0.39 μg/ml ranging from 0.19-0.65 μg/ml), and their clinical signs were reviewed. Thoracic radiographs were evaluated for the presence of pneumomediastinum, lung patterns (interstitial or alveolar) and their locations (caudodorsal, cranioventral, diffuse, or symmetrical), subcutaneous emphysema, pneumoretroperitoneum, and pneumothorax. Results The most common clinical signs were dyspnea (11/11, 100%) and anorexia (9/11, 82%). Pneumomediastinum (10/11, 91%) and symmetrically increased lung opacity (7/11, 65%) were the most common radiographic features. Pneumothorax (3/11, 27%), pleural effusion (3/11, 27%), subcutaneous emphysema (2/11, 18%), and pneumoretroperitoneum (1/5, 20%) were the less common findings. None of the dogs survived. Conclusion Pneumomediastinum and diffuse or symmetrical interstitial or alveolar lung patterns are the most common radiographic features in dogs with paraquat intoxication. Clinical relevance In countries where this herbicide is not banned, paraquat intoxication should be considered if dogs with no history of trauma present with pneumomediastinum.

Use of low-molecular-weight heparin in severe paraquat poisoning: a case report

BackgroundAcute paraquat ingestion remains a leading cause of mortality in developing countries. There is currently no evidence that treatment with high-dose immunosuppressants and antioxidants improves survival in patients with paraquat poisoning, and better options are urgently needed. Here, we describe the unexpected survival and recovery of a patient with a potentially fatal paraquat poisoning.Case presentationAfter ingesting 28 mL of paraquat (20% ion w/v), confirmed by a deep blue color in the urine dithionite test (UDT), a 17-year-old Hispanic Colombian boy was treated according to the hospital protocol with cyclophosphamide, methylprednisolone, N-acetylcysteine, vitamin E and propranolol. Gastrointestinal endoscopy showed extensive ulceration and necrosis. As a novelty, enoxaparin at a single dose of 60 mg was added to his treatment. Despite the evidence of severe mucosal burns in the gastrointestinal tract and high paraquat concentrations found in the UDT, the clinical condition began to improve after 1 day of treatment, with full recovery and discharge from hospital after 21 days.ConclusionsAlthough the amount of paraquat ingested by the patient was large and the UDT indicated severe poisoning with a somber prognosis, unexpected survival of the patient was observed, and the addition of enoxaparin was the only change from the standard treatment.

The Successful Treatment of High Lethal Dose ‎Paraquat Poisoning With Hemoperfusion

Paraquat (PQ), as an herbicide, is mostly used by farmers, especially in the north-west of Iran. Easy access to PQ is the reason for PQ intoxication in farm­ers. However, poisoning with PQ is rare. Most of the PQ-poisoned patients ingest it deliberately and following a suicidal attempt. PQ poisoning treatment has a poor outcome; only a small dose of slightly more than 10 mL PQ could be harmful and damage lungs forever. Under the conditions of no specific clinical feature, proper history, and diagnostic test, diagnosis is usually difficult. The ingestion of PQ in toxic doses could be fatal, destroying the lungs, kidney, heart, gastrointestinal tract, liver, and other organs. To remove PQ from the blood and intoxicants, one of the best recommendations is Hemo­perfusion (HP), as an extracorporeal method. In this case report, according to our treatments, early management of high lethal dose PQ poisoning, especially with HP could reduce the morbidity and mortality rates.

Prevention of Pulmonary Fibrosis in a Child Surviving Paraquat Ingestion

Prevention of Pulmonary Fibrosis in a Child Surviving Paraquat Ingestion

Prevention of Pulmonary Fibrosis in a Child Surviving Paraquat Ingestion

Prevention of Pulmonary Fibrosis in a Child Surviving Paraquat Ingestion William E. Novotny1, 3, Michael Beuhler2, Cindy Keel3, William J. Meggs1, 3 1East Carolina University Brody School of Medicine, Greenville North Carolina USA, 2Carolinas Poison Control, Charlotte North Carolina USA, 3Vidant Medical Center, Greenville, North Carolina USA Background: Mild to moderate paraquat poisoning is associated with a 40% mortality rate. Mitigation of acute alveolar injury and chronic lung fibrosis depends …

Evaluation of the effect of hemodialysis on paraquat poisoning in patients in a Tertiary Care Hospital, West Bengal, India: A cross-sectional study

Background: Among the class of organophosphates, paraquat remains the commonly used herbicidal compound for self-poisoning in developing countries. Ingestion of paraquat is a leading cause of fatal poisoning in many parts of the world. The absence of any standard guidelines on the treatment of patients with paraquat self-poisoning remains an area of scientific research. The treatment varies from various combinations of immune-modulation, antioxidant therapy, hemoperfusion, and hemodialysis (HD). Aims and Objectives: The present study was undertaken to evaluate the role of early initiation HD in the determination of prognosis in the case of paraquat poisoning. Materials and Methods: This cross-sectional study was conducted on the patients suffering from paraquat poisoning, attending the Medicine ward of R. G. Kar Medical College, Kolkata. The patients were subjected to HD and blood was collected before and after therapy. Demographic characteristics of the patients, mortality rate, hepatic, and renal markers in serum were estimated. Results: In the present study, 61 patients with paraquat poisoning were considered following all the inclusion and exclusion criteria. Of 61 patients, 16 patients (26.2%) survived 2 weeks of hospital stay, whereas 45 (73.8%) patients expired. Among the survivors, the mean value of the day of starting dialysis was 1.13 days in contrast to 2 days among the non-survivors. These data showed a significant correlation with mortality with P < 0.0001. Conclusion: The present study, thus, highlighted the fact that early detection and immediate therapeutic action can reduce the risk of mortality in patients suffering from paraquat poisoning.

Silymarin as a Promising Potential Therapeutic Agent for Treatment of Patients with Paraquat Poisoning: An Issue that Merits Further Research.

Having an extremely toxic compound for humans and most animals, paraquat (PQ) is known as one of the most frequently used herbicides. Accordingly, PQ poisoning has been recognized as a serious medical problem across the world, with a severe case fatality rate (CFR). In this respect; accidental or intentional ingestion of PQ, even in a small amount, can be significantly associated with poor clinical prognosis and increased mortality. Moreover; inherent toxicity of PQ, absence of specific antidotes, as well as lack of effective treatments have been principally attributed to high fatality of PQ poisoning. Once PQ is ingested, it can be absorbed through skin and the digestive and respiratory system and often progresses to multi-organ failure, particularly the lungs as the main target. In this respect, PQ accumulates predominantly in the lungs and can lead to lung fibrosis, pneumonitis, and consequently respiratory failure and death. Given the nonexistence of specific and widely accepted guidelines for treatment of PQ poisoning, a range of conservative therapeutic modalities have been proposed and administered by clinicians to moderate PQ absorption and to prevent organ failure in these patients. In spite of this, PQ-induced mortality rate is high and disappointing.

Innate immune responses to paraquat exposure in a Drosophila model of Parkinson\u2019s disease

Parkinson’s disease (PD) is a progressive, neurodegenerative movement disorder characterized by the loss of dopaminergic (DA) neurons. Limited understanding of the early molecular pathways associated with the demise of DA neurons, including those of inflammatory exacerbation of neurodegeneration, is a major impediment to therapeutic development. Recent studies have implicated gene-environment interactions in PD susceptibility. We used transcriptomic profiling in a Drosophila PD model in response to paraquat (PQ)-induced oxidative stress to identify pre-symptomatic signatures of impending neuron dysfunction. Our RNAseq data analysis revealed extensive regulation of innate immune response genes following PQ ingestion. We found that PQ exposure leads to the activation of the NF-κB transcription factor, Relish, and the stress signaling factor JNK, encoded by the gene basket in Drosophila. Relish knockdown in the dopaminergic neurons confers PQ resistance and rescues mobility defects and DA neuron loss. Furthermore, PQ-induced toxicity is mediated through the immune deficiency signaling pathway. Surprisingly, the expression of Relish-dependent anti-microbial peptide (AMPs) genes is suppressed upon PQ exposure causing increased sensitivity to Gram-negative bacterial infection. This work provides a novel link between PQ exposure and innate immune system modulation underlying environmental toxin-induced neurodegeneration, thereby underscoring the role of the innate immune system in PD pathogenesis.

Systemic Paraquat Intoxication Presenting with Peripheral Ulcerative Keratitis: A Case Report and Literature Review

ABSTRACT Purpose To describe a rare case of systemic paraquat poisoning presenting with peripheral ulcerative keratitis Methods Case report and literature review Results Two days after a mouthful of paraquat ingestion, a 48-year-old man presented with painful oral ulcers, abnormal liver functions, and acute kidney injury, followed by the development of crescent-shaped corneal erosions along the limbus and progressive visual impairment in both eyes. Paraquat-induced peripheral ulcerative keratitis was suspected and the patient was treated with intensive topical steroid along with systemic steroid. He recovered completely with good visual outcomes after treatment. Conclusions Peripheral ulcerative keratitis is usually an immune-mediated ocular condition, and may be a complication associated with systemic paraquat poisoning. Proper diagnosis and adequate treatment are important for visual recovery.

Paraquat Poisoning in Children: A 5-Year Review.

Paraquat is an herbicide that is highly toxic to humans. Paraquat ingestion is a common cause of fatal poisoning in many areas of Asia. The aim of the study was to analyze the characteristics of children with acute paraquat poisoning. This study was a retrospective analysis of case exposure to paraquat poisoning as reported to the Department of Pediatrics in The West China Second University Hospital of Sichuan University between January 2012 and December 2017. The data of these patients were extracted from the electronic health records and analyzed. A total of 123 children with paraquat poisoning were included in the study. The study showed that 67.5% of these children (83/123) were accidentally exposed to paraquat, whereas 32.5% (40/123) had intentionally ingested paraquat. The 0- to 2.9-year age group had the largest number of cases (30% of the total). One hundred (81.3%) children were discharged with a better health condition. Two children were dead at the time of hospitalization because of respiratory failure. Most children (87.8%) with paraquat poisoning were left-behind children. Paraquat poisoning did not frequently occur in the winter. Left-behind children living in rural areas have a high risk of paraquat poisoning. Interventions and policies are urgently needed to prevent paraquat poisoning in children. Preventative efforts are the most important measures.

Paraquat poisoning: An unusual lung toxicity

Paraquat poisoning is an uncommonly faced but fatal poisoning. Paraquat gets accumulated in lung tissues by active absorption against concentration gradient and causes oxidative injury. We hereby, describe a fourteen years old boy admitted following ingestion of paraquat (approximately 10–15ml). Immediately after ingestion, child developed oral ulceration and recurrent vomiting. Since day 4 of ingestion the boy developed respiratory distress which worsened over the week requiring initiation of mechanical ventilation at very high settings. He was also treated with methylprednisolone pulse therapy for paraquat toxicity. There was transient improvement in oxygenation parameters following these therapies. Unfortunately, the hypoxemia worsened despite initial improvement and he finally succumbed on day 14 of illness. It appears that initiation of immunosuppressive therapy early in the course of ingestion even when the patient is apparently free of any respiratory complaints may alter the course of moderate to severe poisoning.

A Synthetic Receptor as a Specific Antidote for Paraquat Poisoning.

Accidental or suicidal ingestion of the world's most widely used herbicide, paraquat (PQ), may result in rapid multi-organ failure with a 60% fatality rate due to the absence of an effective detoxification solution. Effective, specific antidotes to PQ poisoning have been highly desired.Methods: The binding constant of PQ and a synthetic receptor, cucurbit[7]uril (CB[7]), was first determined in various pH environments. The antidotal effects of CB[7] on PQ toxicity were firstly evaluated with in-vitro cell lines. With in-vivo mice models, the pharmacokinetics and the biodistribution of PQ in major organs were determined to evaluate the influence of CB[7] on the oral bioavailability of PQ. Major organs' injuries and overall survival rates of the mice were systemically examined to evaluate the therapeutic efficacy of CB[7] on PQ poisoning.Results: We demonstrate that CB[7] may complex PQ strongly under various conditions and significantly reduce its toxicity in vitro and in vivo. Oral administration of PQ in the presence of CB[7] in a mouse model significantly decreased PQ levels in the plasma and major organs and alleviated major organs' injuries, when compared to those of mice administered with PQ alone. Further studies indicated that oral administration of CB[7] within 2 h post PQ ingestion significantly increased the survival rates and extended the survival time of the mice, in contrast to the ineffective treatment by activated charcoal, which is commonly recommended for PQ decontamination.Conclusion: CB[7] may be used as a specific oral antidote for PQ poisoning by strongly binding with PQ and inhibiting its absorption in the gastrointestinal tracts.

Neuroprotective action of Eicosapentaenoic (EPA) and Docosahexaenoic (DHA) acids on Paraquat intoxication in Drosophila melanogaster

Several studies have shown the protective effects of dietary enrichment of omega-3 (ω-3) long-chain fatty acids in several animal models of neurodegenerative diseases. Here we investigate if eicosapentaenoic (EPA) and Docosahexaenoic (DHA) acids (ω-3) protect against neurodegeneration mediated by the exposure to a widely used herbicide Paraquat (PQ) (1,1ʹ-dimethyl-4-4ʹ-bipyridinium dichloride), focusing on mitochondrial metabolism using Drosophila melanogaster as a model. Dietary ingestion of PQ for 3 days resulted in the loss of citrate synthase content, respiratory capacity impairment and exacerbated H2O2 production per mitochondrial unit related to complex I dysfunction, and high lactate accumulation in fly heads. PQ intoxication lead to 1) the loss of ELAV (embryonic lethal abnormal vision) and α-spectrin, essential proteins of neuronal viability and synaptic stability; 2) increased gamma-secretase activity, an enzyme related to APP release; and 3) increased the amyloid fibrils contents. All these toxic effects induced by PQ were prevented by concomitant dietary ingestion of EPA/DHA, suggesting that a neuroprotective effect of ω-3 also involves mitochondrial protection. In conclusion, concomitant EPA and DHA ingestion protects against PQ-induced neuronal and mitochondrial dysfunctions frequently found in neurodegenerative processes reinforcing its protective role against environmental neurodegenerative diseases.

Cellular uptake of paraquat determines subsequent toxicity including mitochondrial damage in lung epithelial cells.

Paraquat (PQ) is one of the commonly used herbicides in the world, despite its high toxicity. The ingestion of PQ accidentally or intentionally causes severe damage in diverse organs including the lung. Pulmonary fibrosis triggered by PQ accumulation in the lung epithelial cells is one of the major causes of death. This study investigated the intracellular accumulation of PQ, reactive oxygen species (ROS) generation and mitochondrial injury using two lung epithelial cell lines A549 and BEAS-2B (BEAS). Although A549 exhibit greater resistance to oxidative stress than BEAS, a cytotoxicity assay for PQ demonstrated that EC50 for lethality in A549 was 7 times lower than that in BEAS. When exposed to PQ at a concentration around EC50 for lethality, the amount of ROS generated in A549 was as low as that in BEAS. Conversely, the cellular concentration of PQ in A549 after exposure was higher than that in BEAS, which suggests a distinct difference in the susceptibility to PQ between these cell lines. After a 16 h exposure to PQ, mitochondrial membrane potential (MMP) decreased in A549, but decreased only slightly in BEAS even following a 30 h exposure. PQ-exposed A549 reduced an accumulation of PTEN-induced kinase 1 (PINK1), which works in degradation of damaged mitochondria, following the decrease of MMP, whereas PQ did not decline the PINK1 in BEAS. These results suggest that mitochondrial dysfunction due to cellular accumulation of PQ might contribute to the PQ-provoked toxicity more than the ROS generation in the lung epithelial cells.

Acute Kidney Injury Followed by Paraquat Poisoning With Relative Absence of Pulmonary and Renal Complaints : Story of a Survivor

A 16 years old girl admitted in the hospital after paraquat ingestion. She had oral ulceration and difficulty in swallowing. All her vital signs were normal including clear both lung fields. After few days, her tongue found coatedwith whitish debris. Her chest X-ray was normal but creatinine was 7.45 mg/dL despite normal urine output. After 2 cycle ofhemo dialysis her creatinine became normal. She had 2 unit of blood transfusion.After 3 weeks of hospital treatments she wasdischarged from hospital with all normal routine investigations including High Resolution Computed Tomography (HRCT) of both lungs. After one month of home stay she was alright on her last follow up.&#x0D; JCMCTA 2018 ; 29 (1) : 75-77

Predictive value of the maximum serum creatinine value and growth rate in acute paraquat poisoning patients

This retrospective and a single-center study evaluated the prognostic value of the maximum serum creatinine value (maxCr) and the maximum serum creatinine growth rate (Vmax) after paraquat (PQ) ingestion. One hundred and seventy-one patients with PQ poisoning were treated with a uniform protocol. Demographic variables, clinical manifestations, relevant laboratory data, maxCr and Vmax of all patients were recorded and calculated. The time after PQ ingestion of maxCr and Vmax were also recorded. Vmax and MaxCr exhibited statistically significant differences between the survivor (n = 53) and death (n = 118) groups. Vmax appeared earlier in the death group than the survivor group. Regard to the receiver operating characteristic (ROC) curve analysis, Vmax had an AUC of 0.861 (95% CI, 0.801–0.921) and the optimal cut-off value of 6.21 μmol/(L·h) (sensitivity, 76.3%; specificity, 81.1%). MaxCr had an area under the curve (AUC) of 0.821 (95% CI, 0.752–0.889) and the optimal cut-off value of 225.5 µmol/L (sensitivity, 82.2%; specificity, 67.9%). The comparison of the AUC in the two parameters showed no significant difference, but Vmax appeared earlier than maxCr. Based on binary logistic regression analysis, MaxCr and Vmax both showed strong predictive powers for evaluating the prognosis of acute PQ poisoning patients.

Increased plasma prothrombin time is associated with poor prognosis in patients with paraquat poisoning.

Paraquat can cause severe injury to vascular endothelial cells and lead to coagulation dysfunction when it is taken into the blood by oral ingestion. In this study, we aim to find a routine coagulation index to serve as an indicator of outcome in patients with acute paraquat poisoning. Between January 2012 and December 2016, 209 patients who attempted suicide by oral ingestion of paraquat were admitted to the emergency room. Routine coagulation indices, including plasma prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fbg), thrombin time (TT), and D-dimer were measured to analyze the trend of changes and their relationship with prognosis. The results showed that the PT and APTT values in the ≥30mL group were significantly greater than those in the <30mL group (both P<.01). Within 1week of admission, PT and APTT values gradually decreased, while Fbg levels gradually increased. Univariate and multivariate Cox regression analysis indicated that sex, ingestion volume, and PT were independent predictors of mortality within 40days. The cumulative survival rates differed significantly (P=.001) between patients with PT <12seconds and PT ≥12seconds. Coagulation status in patients with PQ poisoning was closely related to prognosis. Routine monitoring of coagulation function, particularly PT in plasma, is helpful for analysis of the condition and prognosis of patients with PQ poisoning.

Vitamin D treatment abrogates the inflammatory response in paraquat-induced lung fibrosis

A high incidence of intentional or accidental paraquat (PQ) ingestion is related to irreversible lung fibrosis and no effective therapy is currently available. Vitamin D has emerged with promising results as an immunomodulatory molecule when abrogating the inflammatory responses of lung diseases. Therefore, we have investigated the role of vitamin D treatments on PQ-induced lung fibrosis in male C57/BL6 mice. Lung fibrosis was induced by a single injection of PQ (10 mg/kg; i.p.). The control group received PQ vehicle. Seven days later, after the PQ injection or the vehicle injection, the mice received vitamin D (5 μg/kg, i.p., once a day) or vehicle, for a further 7 days. Twenty-four hours after the last dose of vitamin D or the vehicle, the analysis were performed. The vitamin D treatments reduced the number of leukocytes in their BALF and they decreased the IL-6, IL-17, TGF-beta and MMP-9 levels and the abrogated collagenase deposits in their lung tissues. Conversely, the vitamin D treatments increased the resolvin D levels in their BALF. Moreover, their tracheal contractility was also significantly reduced by the vitamin D treatments. Altogether, the data that was obtained showed a promising use of vitamin D, in treating the lung fibrosis that had been induced by the PQ intoxications. This may improve its prognostic use for a non-invasive and low cost therapy.