Leukotriene-mediated neuroinflammation, toxic brain damage, and neurodegeneration in acute methanol poisoning

Figures & data

Table 1. Admission laboratory data in the patients with acute serum LT measurements (Group I) and in the follow-up group of survivors 2 years after discharge (Group II).

Groups	MetOH, mg/L	EtOH, mg/L	Formic acid, mg/L	pH	HCO3^-(mM)	Lactate, (mM)	BE, (mM)	Glucose, (mM)	Creatinine, (μM)	AG (mM)	Time, h
Group I  (n = 28)	1220 ± 420	160 ± 130	590 ± 140	7.06 ± 0.10	9.1 ± 2.7	5.4 ± 2.0	−18.2 ± 5.6	9.7 ± 2.0	95.0 ± 17.0	29.7 ± 4.0	38.4 ± 8.3
Group II  (n = 36)	1340 ± 440	490 ± 340	500 ± 180	7.19 ± 0.27	12.4 ± 2.6	3.6 ± 1.6	−15.2 ± 3.9	7.6 ± 1.2	93.0 ± 13.0	27.1 ± 3.9	33.5 ± 8.0
pI/Control	0.706	0.078	0.419	0.392	0.088	0.184	0.355	0.079	0.837	0.355	0.408

LTs: leukotrienes; MetOH: serum methanol on admission; EtOH: serum ethanol concentration on admission; Formic acid: serum formic acid on admission; BE: base excess; AG: anion gap; pH: arterial blood pH; HCO₃^-: bicarbonate concentration; Lactate: serum lactate on admission; Glucose: serum glucose on admission; Creatinine: serum creatinine on admission; Time: time from methanol ingestion to hospital admission and treatment. p < 0.05 was considered as significant.

Figure 1. Box-and-whisker plots of serum LT concentrations measured during hospitalization and in the survivors 2 years after discharge (Follow-up). Acute Cmax – maximum serum LT concentrations measured during hospitalization; Acute Cmean – mean serum LT concentrations during the observation period with acute methanol poisoning. Mean (dotted line), standard error of the mean (SEM, box), and 95%CI of the mean (whiskers) are presented. ***p < 0.001.

Table 2. Serum LT concentrations measured during hospitalization (Group I) and in the follow-up group of survivors (Group II) 2 years after discharge (means ± CI95%)^b.

Patients	LTC4, Cmax, pg/mL	LTC4, Cmean, pg/mL	LTD4, Cmax, pg/mL	LTD4, Cmean, pg/mL	LTE4, Cmax, pg/mL	LTE4, Cmean, pg/mL	LTB4, Cmax, pg/mL	LTB4, Cmean, pg/mL
Group I (n = 28)	80.7 ± 5.6	67.0 ± 3.8	51.0 ± 6.6	35.4 ± 3.2	64.2 ± 6.0	49.8 ± 4.5	59.8 ± 6.2	44.4 ± 4.7
Group II (n = 36)	47.9 ± 4.5	47.9 ± 4.5	23.1 ± 2.1	23.1 ± 2.1	26.2 ± 3.9	26.2 ± 3.9	27.2 ± 1.4	27.2 ± 1.4
PI/Control	<0.001	<0.001	<0.001	<0.001	<0.001	<0.001	<0.001	<0.001
Survived (n = 22)	83.9 ± 6.2	69.3 ± 4.0	54.2 ± 8.0	36.9 ± 3.8	66.8 ± 6.7	51.6 ± 4.6	61.0 ± 6.9	45.0 ± 5.2
Died (n = 6)	68.8 ± 8.6	58.6 ± 7.6	39.5 ± 2.9	29.9 ± 2.3	55.0 ± 15.0	43.0 ± 16.0	55.0 ± 19.0	42.0 ± 15.0
Died^a (n = 5)	66.0 ± 6.1	55.8 ± 2.6	39.6 ± 3.9	29.7 ± 3.0	49.2 ± 7.5	37.4 ± 6.1	47.8 ± 2.2	36.5 ± 3.3
p survived/died	0.023	0.017	0.002	0.003	0.004	0.0140	0.455	0.646
P^asurvived/died	<0.001	<0.001	0.002	0.003	<0.001	0.008	0.001	0.007
No sequelae (n = 11)	88.2 ± 9.2	71.4 ± 5.7	61.0 ± 14.0	39.8 ± 6.5	73.5 ± 9.8	56.5 ± 7.0	69.0 ± 11.0	51.0 ± 9.3
Sequelae (n = 11)	79.6 ± 9.3	67.2 ± 6.4	47.7 ± 7.9	34.0 ± 4.3	60.2 ± 8.7	46.6 ± 5.3	52.6 ± 6.4	39.0 ± 3.0
p no sequelae/sequelae	0.178	0.315	0.114	0.126	0.044	0.027	0.011	0.022

LT: leukotrienes; C_max: maximum serum LT concentrations measured during hospitalization; C_mean: mean serum LT concentrations during the observation period with acute methanol poisoning; No sequelae: the patients in Group I survived without health sequelae of acute methanol poisoning; Sequelae: the patients in Group I survived with long-term visual and/or CNS sequelae of acute methanol poisoning. p < 0.05 (bold numbers) was considered as significant.

^a After elimination of the outlier died due to liver failure caused by alcoholic cirrhosis 2 months after admission.

^b Normal reference ranges in blood serum of healthy human adults for LTC4: 38.0 ± 19.0 pg/mL, for LTD4: 20.9 ± 2.0 pg/mL, for LTE4: 13.6 ± 6.6 pg/mL, and for LTB4: 32.6 ± 2.1 pg/mL [57].

Figure 2. Dynamics of acute serum LT concentrations changes during the observation period in the patients hospitalized with acute methanol poisoning.

Table 3. Follow-up serum LT concentrations measured 2 years after discharge (Group II) in survivors without sequelae versus survivors with long-term visual and/or CNS sequelae of poisoning (n = 36; means ± CI95%)^a.

Patients	LTC4, pg/mL	LTD4, pg/mL	LTE4, pg/mL	LTB4, pg/mL
No sequelae (n = 17)	46.4 ± 8.5	23.6 ± 3.3	25.2 ± 6.4	27.6 ± 2.1
Sequelae (n = 19)	49.4 ± 4.6	22.5 ± 2.9	27.1 ± 5.4	26.8 ± 2.1
p	0.528	0.604	0.646	0.587

LT: leukotrienes; No sequelae: the patients in the follow-up Group II survived without health sequelae of acute methanol poisoning; Sequelae: the patients in the follow-up Group II survived with long-term visual and/or CNS sequelae of acute methanol poisoning. p < 0.05 was considered as significant.

^a Published normal reference ranges in blood serum of healthy human adults for LTC4: 38.0 ± 19.0 pg/mL, for LTD4: 20.9 ± 2.0 pg/mL, for LTE4: 13.6 ± 6.6 pg/mL, and for LTB4: 32.6 ± 2.1 pg/mL [57].

Figure 3. Decrease of serum LT concentrations measured during hospitalization (“Acute”) versus LT concentrations measured 2 years after discharge in the same patients (“Follow-up”).

Psychogios N, Hau DD, Peng J, et al. The human serum metabolome. PLoS One. 2011;6:e16957.

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