Role of activation of lipid peroxidation in the mechanisms of acute methanol poisoning

0494639 - ÚFCH JH 2019 RIV US eng J - Journal Article
Hlušička, J. - Löster, T. - Lischková, L. - Vaněčková, M. - Seidl, Z. - Diblík, P. - Kuthan, P. - Urban, P. - Navrátil, Tomáš - Kačer, P. - Zakharov, S.
Role of activation of lipid peroxidation in the mechanisms of acute methanol poisoning.
Clinical Toxicology. Roč. 56, č. 10 (2018), s. 893-903. ISSN 1556-3650. E-ISSN 1556-9519
Institutional support: RVO:61388955
Keywords : methanol poisoning * lipid peroxidation * neuroinflammation
OECD category: Physical chemistry
Impact factor: 4.398, year: 2018

Context: The role of activation of lipid peroxidation in the mechanisms of acute methanol poisoning
has not been studied.
Objective: We measured the concentrations of lipid peroxidation markers in acutely intoxicated
patients with known serum concentrations of methanol and leukotrienes.
Methods: Blood serum samples were collected from 28 patients hospitalized with acute intoxication
and from 36 survivors 2 years after discharge. In these samples, concentrations of 4-hydroxy-trans-2-
hexenal (HHE), 4-hydroxynonenal (HNE), and malondialdehyde (MDA) were measured using the
method of liquid chromatography-electrospray ionization-tandem mass spectrometry.
Results: The maximum acute serum concentrations of all three lipid oxidative damage markers were
higher than the follow-up serum concentrations: HNE 71.7 ± 8.0 ng/mL versus 35.4 ± 2.3 ng/mL, p<.001,
HHE 40.1 ± 6.7 ng/mL versus 17.7 ± 4.1 ng/mL, p<.001, MDA 80.0 ± 7.2 ng/mL versus 40.9 ± 1.9 ng/mL,
p<.001. The survivors without methanol poisoning sequelae demonstrated higher acute serum
concentrations of the markers than the patients with sequelae. A correlation between measured
markers and serum leukotrienes was present: HNE correlated with LTC4 (r=0.663), LTD4 (r=0.608),
LTE4 (r=0.771), LTB4 (r=0.717), HHE correlated with LTC4 (r=0.713), LTD4 (r=0.676), LTE4
(r=0.819), LTB4 (r=0.746), MDA correlated with LTC4 (r=0.785), LTD4 (r=0.735), LTE4 (r=0.814),
LTB4 (r=0.674), all p<.001. Lipid peroxidation markers correlated with anion gap (r=-0.428, -0.388,
-0.334, p=.026, .045, .080 for HNE, HHE, MDA, respectively). The follow-up serum concentrations of
lipid oxidation markers measured in survivors with and without visual/neurological sequelae 2 years
after discharge did not differ.
Conclusion: Our results demonstrate that lipid peroxidation plays a significant role in the mechanisms
of acute methanol poisoning. The acute concentrations of three measured biomarkers were elevated
in comparison with the follow-up concentrations. Neuronal membrane lipid peroxidation seems to
activate leukotriene-mediated inflammation as a part of the neuroprotective mechanisms. No cases of
persistent elevation were registered among the survivors 2 years after discharge.
Permanent Link: http://hdl.handle.net/11104/0287746