Postmortem analyses unveil the poor efficacy of decontamination, anti-inflammatory and immunosuppressive therapies in paraquat human intoxications.
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.


RESULTS
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-kappaB) activation and excessive collagen deposition.


CONCLUSIONS
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.
Faculty of Medicine, University of Porto, Porto, Portugal. ricardinis@sapo.pt
Ricardo Jorge
RJ
Dinis-Oliveira
Paula Guedes
PG
de Pinho
Liliana
L
Santos
Helena
H
Teixeira
Teresa
T
Magalhães
Agostinho
A
Santos
Maria
M
de Lourdes Bastos
Fernando
F
Remião
José Alberto
JA
Duarte
Félix
F
Carvalho
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001344:Autopsy; D003094:Collagen / Q000378:metabolism; D005260:Female; D049429:Forensic Pathology / Q000379:methods*; D006540:Herbicides / Q000506:poisoning*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D010269:Paraquat / Q000506:poisoning*; D011041:Poisoning / Q000401:mortality*
D000893:Anti-Inflammatory Agents; D006540:Herbicides; D007166:Immunosuppressive Agents; D016328:NF-kappa B; D003094:Collagen; D010269:Paraquat