50
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Postmortem Analyses Unveil the Poor Efficacy of Decontamination, Anti-Inflammatory and Immunosuppressive Therapies in Paraquat Human Intoxications

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Fatalities resulting from paraquat (PQ) self-poisonings represent a major burden of this herbicide. Specific therapeutic approaches have been followed to interrupt its toxic pathway, namely decontamination measures to prevent PQ absorption and to increase its excretion from organism, as well as the administration of anti-inflammatory and immunosuppressive drugs. Until now, none of the postmortem studies resulting from human PQ poisonings have assessed the relationship of these therapeutic measures with PQ toxicokinetics and related histopathological lesions, these being the aims of the present study.

          Methodology/Principal Findings

          For that purpose, during 2008, we collected human fluids and tissues from five forensic autopsies following fatal PQ poisonings. PQ levels were measured by gas chromatography-ion trap mass spectrometry. Structural inflammatory lesions were evaluated by histological and immunohistochemistry analysis. The samples of cardiac blood, urine, gastric and duodenal wall, liver, lung, kidney, heart and diaphragm, showed quantifiable levels of PQ even at 6 days post-intoxication. Structural analysis showed diffused necrotic areas, intense macrophage activation and leukocyte infiltration in all analyzed tissues. By immunohistochemistry it was possible to observe a strong nuclear factor kappa-B (NF-κB) activation and excessive collagen deposition.

          Conclusions/Significance

          Considering the observed PQ levels in all analyzed tissues and the expressive inflammatory reaction that ultimately leads to fibrosis, we conclude that the therapeutic protocol usually performed needs to be reviewed, in order to increase the efficacy of PQ elimination from the body as well as to diminish the inflammatory process.

          Related collections

          Most cited references41

          • Record: found
          • Abstract: found
          • Article: not found

          Paraquat poisonings: mechanisms of lung toxicity, clinical features, and treatment.

          Paraquat dichloride (methyl viologen; PQ) is an effective and widely used herbicide that has a proven safety record when appropriately applied to eliminate weeds. However, over the last decades, there have been numerous fatalities, mainly caused by accidental or voluntary ingestion. PQ poisoning is an extremely frustrating condition to manage clinically, due to the elevated morbidity and mortality observed so far and due to the lack of effective treatments to be used in humans. PQ mainly accumulates in the lung (pulmonary concentrations can be 6 to 10 times higher than those in the plasma), where it is retained even when blood levels start to decrease. The pulmonary effects can be explained by the participation of the polyamine transport system abundantly expressed in the membrane of alveolar cells type I, II, and Clara cells. Further downstream at the toxicodynamic level, the main molecular mechanism of PQ toxicity is based on redox cycling and intracellular oxidative stress generation. With this review we aimed to collect and describe the most pertinent and significant findings published in established scientific publications since the discovery of PQ, focusing on the most recent developments related to PQ lung toxicity and their relevance to the treatment of human poisonings. Considerable space is also dedicated to techniques for prognosis prediction, since these could allow development of rigorous clinical protocols that may produce comparable data for the evaluation of proposed therapies.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            Prediction of outcome after paraquat poisoning by measurement of the plasma paraquat concentration

            Background: Paraquat is a herbicide with a good occupational safety record, but a high mortality after intentional ingestion that has proved refractory to treatment. For nearly three decades paraquat concentration–time data have been used to predict the outcome following ingestion. However, none of the published methods has been independently or prospectively validated. We aimed to use prospectively collected data to test the published predictive methods and to determine if any is superior. Methods: Plasma paraquat concentrations were measured on admission for 451 patients in 10 hospitals in Sri Lanka as part of large prospective cohort study. All deaths in hospital were recorded; patients surviving to hospital discharge were followed up after 3 months to detect delayed deaths. Five prediction methods that are based on paraquat concentration–time data were then evaluated in all eligible patients. Results: All methods showed comparable performance within their range of application. For example, between 4- and 24-h prediction of prognosis was most variable between Sawada and Proudfoot methods but these differences were relatively small [specificity 0.96 (95% CI: 0.90–0.99) vs. 0.89 (0.82–0.95); sensitivity 0.57 vs. 0.79, positive and negative likelihood ratios 14.8 vs. 7.40 and 0.44 vs. 0.23 and positive predictive values 0.96 vs. 0.92, respectively]. Conclusions: All five published methods were better at predicting death than survival. These predictions may also serve as tools to identify patients who need treatment and for some assessment to be made of new treatments that are trialled without a control group.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Association between plasma paraquat level and outcome of paraquat poisoning in 375 paraquat poisoning patients.

              Paraquat poisoning by ingestion is often fatal. Many studies have investigated treatment modalities and predictor parameters, but there is no standard treatment. Plasma paraquat concentration seems a valid predictable parameter of survival. In order to achieve uniform treatment, including extracorporeal elimination and antioxidant therapy, the outcome of paraquat poisoning based on plasma paraquat level needs to be investigated. This study included 375 paraquat poisoning patients who were diagnosed by means of plasma paraquat concentration within 24 hours after ingestion in the Institute of Pesticide Poisoning of Soonchunhyang University Cheonan Hospital, Korea, from January 2005 to December 2006. All patients were treated according to a uniform protocol including extracorporeal elimination and antioxidant therapy. Plasma paraquat concentration was measured by high-performance liquid chromatography. The mean age of the paraquat-intoxicated patients was 48.42 +/- 6.75. One hundred ten patients (29.3%) survived. The upper limit of plasma paraquat concentration in survivors was 2.64 at 3 hour. All patients with plasma paraquat level above 3.44 died. The minimum paraquat level of the deaths was very low (0.12 microg/ml at 5 hours; 0.02 microg/ml at 12 hours; 0.01 microg/ml at 24 hours). Our data showed that plasma paraquat concentration is good predictor of survivors but is not good predictor of non-survivors in the low plasma paraquat level.
                Bookmark

                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2009
                25 September 2009
                : 4
                : 9
                : e7149
                Affiliations
                [1 ]Faculty of Medicine, University of Porto, Porto, Portugal
                [2 ]Department of Clinical Analysis and Public Health, Center of Research in Health Technologies (CITS)-IPSN-CESPU, CRL, Vila Nova de Famalicão, Portugal
                [3 ]REQUIMTE, Department of Toxicology, Faculty of Pharmacy, University of Porto, Porto, Portugal
                [4 ]Center of Forensic Sciences, Foundation for Science and Technology, Lisbon, Portugal
                [5 ]Biomedical Sciences Institute Abel Salazar, University of Porto, Porto, Portugal
                [6 ]National Institute of Legal Medicine I.P., Coimbra, Portugal
                [7 ]CIAFEL, Faculty of Sport, University of Porto, Porto, Portugal
                Sun Yat-Sen University, China
                Author notes

                Conceived and designed the experiments: RJDO PGdP MdLB FR JD FC. Performed the experiments: RJDO PGdP LS AS FR JD FC. Analyzed the data: RJDO PGdP LS HT TM AS MdLB FR JD FC. Contributed reagents/materials/analysis tools: RJDO PGdP HT TM AS MdLB FR JD FC. Wrote the paper: RJDO PGdP LS HT TM AS MdLB FR JD FC.

                Article
                09-PONE-RA-11303
                10.1371/journal.pone.0007149
                2745573
                19779613
                de9596b0-fd6d-4e93-a9dc-ade6d14b26ab
                Dinis-Oliveira et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 27 June 2009
                : 20 August 2009
                Page count
                Pages: 13
                Categories
                Research Article
                Non-Clinical Medicine/Forensic Medicine
                Non-Clinical Medicine/Medical Law
                Pharmacology/Drug Development

                Uncategorized
                Uncategorized

                Comments

                Comment on this article