Leukotriene-mediated neuroinflammation, toxic brain damage, and neurodegeneration in acute methanol poisoning.
BACKGROUND
The role of neuroinflammation in methanol-induced toxic brain damage has not been studied.


OBJECTIVE
We studied acute concentrations and the dynamics of leukotrienes (LT) in serum in hospitalized patients with acute methanol poisoning and in survivors.


METHODS
Series of acute cysteinyl-LT and LTB4 concentration measurements were performed in 28/101 hospitalized patients (mean observation time: 88 ± 20 h). In 36 survivors, control LT measurements were performed 2 years after discharge.


RESULTS
The acute maximum (Cmax) LT concentrations were higher than concentrations in survivors: Cmaxfor LTC4 was 80.7 ± 5.6 versus 47.9 ± 4.5 pg/mL; for LTD4, 51.0 ± 6.6 versus 23.1 ± 2.1 pg/mL; for LTE4, 64.2 ± 6.0 versus 26.2 ± 3.9 pg/mL; for LTB4, 59.8 ± 6.2 versus 27.2 ± 1.4 pg/mL (all p < 0.001). The patients who survived had higher LT concentrations than those who died (all p < 0.01). Among survivors, patients with CNS sequelae had lower LTE4 and LTB4 than did those without sequelae (both p < 0.05). The LT concentrations increased at a rate of 0.4-0.5 pg/mL/h and peaked 4-5 days after admission. The patients with better outcomes had higher cys-LTs (all p < 0.01) and LTB4 (p < 0.05). More severely poisoned patients had lower acute LT concentrations than those with minor acidemia. The follow-up LT concentrations in survivors with and without CNS sequelae did not differ (all p > 0.05). The mean decrease in LT concentration was 30.9 ± 9.0 pg/mL for LTC4, 26.3 ± 8.6 pg/mL for LTD4, 37.3 ± 6.4 pg/mL for LTE4, and 32.0 ± 8.8 pg/mL for LTB4.


CONCLUSIONS
Our findings suggest that leukotriene-mediated neuroinflammation may play an important role in the mechanisms of toxic brain damage in acute methanol poisoning in humans. Acute elevation of LT concentrations was moderate, transitory, and was not followed by chronic neuroinflammation in survivors.
a Department of Occupational Medicine, First Faculty of Medicine , Charles University , Prague , Czech Republic.|b Toxicological Information Centre, General University Hospital , Prague , Czech Republic.
Sergey
S
Zakharov
a Department of Occupational Medicine, First Faculty of Medicine , Charles University , Prague , Czech Republic.
Katerina
K
Kotikova
a Department of Occupational Medicine, First Faculty of Medicine , Charles University , Prague , Czech Republic.
Olga
O
Nurieva
a Department of Occupational Medicine, First Faculty of Medicine , Charles University , Prague , Czech Republic.|b Toxicological Information Centre, General University Hospital , Prague , Czech Republic.
Jiri
J
Hlusicka
c Institute of Chemical Technology , Prague , Czech Republic.
Petr
P
Kacer
a Department of Occupational Medicine, First Faculty of Medicine , Charles University , Prague , Czech Republic.|d Centre for Industrial Hygiene and Occupational Medicine, National Institute of Public Health , Prague , Czech Republic.
Pavel
P
Urban
e Department of Radiology, First Faculty of Medicine , Charles University and General University Hospital , Prague , Czech Republic.
Manuela
M
Vaneckova
e Department of Radiology, First Faculty of Medicine , Charles University and General University Hospital , Prague , Czech Republic.
Zdenek
Z
Seidl
f Department of Ophthalmology, First Faculty of Medicine , Charles University and General University Hospital , Prague , Czech Republic.
Pavel
P
Diblik
f Department of Ophthalmology, First Faculty of Medicine , Charles University and General University Hospital , Prague , Czech Republic.
Pavel
P
Kuthan
b Toxicological Information Centre, General University Hospital , Prague , Czech Republic.|g Department of Biomimetic Electrochemistry , J. Heyrovský Institute of Physical Chemistry of the AS CR , v.v.i , Prague , Czech Republic.
Tomas
T
Navratil
a Department of Occupational Medicine, First Faculty of Medicine , Charles University , Prague , Czech Republic.|b Toxicological Information Centre, General University Hospital , Prague , Czech Republic.
Daniela
D
Pelclova
D000208:Acute Disease; D001639:Bicarbonates / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D003404:Creatinine / Q000097:blood; D003545:Cysteine / Q000097:blood; D000431:Ethanol / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D005561:Formates / Q000097:blood; D006760:Hospitalization; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007249:Inflammation / Q000139:chemically induced* / Q000473:pathology; D007773:Lactates / Q000097:blood; D015289:Leukotrienes / Q000097:blood*; D008297:Male; D000432:Methanol / Q000097:blood / Q000506:poisoning*; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000139:chemically induced* / Q000473:pathology; D011041:Poisoning / Q000097:blood / Q000188:drug therapy*; D016896:Treatment Outcome
D001639:Bicarbonates; D001786:Blood Glucose; D005561:Formates; D007773:Lactates; D015289:Leukotrienes; C112381:cysteinyl-leukotriene; C030544:formic acid; D000431:Ethanol; D003404:Creatinine; D003545:Cysteine; D000432:Methanol
Neuroinflammation; brain damage; leukotrienes; methanol poisoning; nontraumatic brain injury; sequelae of poisoning