Reactive carbonyl compounds, carbonyl stress, and neuroinflammation in methyl alcohol intoxication

Abstract

Methyl alcohol intoxications are characterized by high lethality and high prevalence of serious visual and brain damage in survivors. The mechanisms of toxic brain damage are complex and the role of carbonyl stress has not been studied yet. We measured the acute and follow-up concentrations of reactive carbonyl compounds in patients with acute methyl alcohol intoxication. Blood samples were collected from 28 subjects hospitalized with confirmed methyl alcohol intoxication and from 36 subjects who survived poisoning 2 years after discharge. Serum concentrations of C6–12 reactive aldehydes were measured by liquid chromatography–electrospray ionization–tandem mass spectrometry. The acute concentrations of all measured reactive aldehydes were higher than the follow-up concentrations: 36.4 ± 4.8 vs. 21.6 ± 5.2 ng cm−3 for C6; 38.9 ± 5 vs. 17.0 ± 2.0 ng cm−3 for C7; 18.8 ± 3.9 vs. 4 ± 0 cm−3 for C8; 36.5 ± 3.9 vs. 19.0 ± 3.0 ng cm−3 for C9; 6.1 ± 0.4 vs. 4.0 ± 0.5 ng cm−3 for C10; 13.6 ± 3.0 vs. 3.7 ± 0.6 ng cm−3 for C11; and 7.8 ± 0.4 vs. 4.7 ± 0.4 ng cm−3 for C12 (all p < 0.001). The patients who survived the intoxication had higher concentration of reactive carbonyl compounds than those who died: 38.6 ± 5.9 vs. 28.3 ± 1.7 ng cm−3 for C6 (p = 0.002); 20.7 ± 4.7 vs. 11.8 ± 1.2 ng cm−3 for C8 (p = 0.001); 37.7 ± 4.8 vs. 31.8 ± 3.8 ng cm−3 for C9 (p = 0.042); and 7.9 ± 0.6 vs. 7.3 ± 0.5 ng cm−3 for C12 (p = 0.022). A significant association was present between severity of metabolic acidosis, anion gap, and the acute concentration of measured biomarkers: r = − 0.39; p = 0.046 for C6; r = − 0.42; p = 0.035 for C7; r = − 0.48; p = 0.012 for C8; r = − 0.39; p = 0.046 for C9; and r = − 0.47; p = 0.015 for C11. The acute concentration of C6–C12 reactive aldehydes positively correlated with the acute serum concentration of leukotrienes (all p < 0.05). Acute elevation of serum concentration of reactive carbonyl compounds suggests that carbonyl stress is involved in the mechanisms of leukotriene-mediated neuroinflammatory response to methyl alcohol-induced toxic brain damage.