Abstract
BackgroundFatalities 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 FindingsFor 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/SignificanceConsidering 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.
Highlights
Paraquat (PQ) poisonings is by far one of the most clinically significant pesticide in terms of morbidity and mortality [1]
All victims were subjected to the same protocol, the differences among them being the plasma concentration of PQ and the survival period
According to the most recent casuistic studies, PQ is responsible for thousands of fatal poisonings due to pesticides exposures [11,12,13,14,15,16]
Summary
Paraquat (PQ) poisonings is by far one of the most clinically significant pesticide in terms of morbidity and mortality [1]. The main target organ for PQ toxicity is the lung as a consequence of its accumulation against a concentration gradient, through the highly developed polyamine uptake system, and due to its capacity to generate huge amounts of pro-oxidant reactive species through a strenuous redox-cycle pathway [1]. 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. 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
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