Enhanced urinary excretion of cysteinyl leukotrienes in patients with acute alcohol intoxication.
OBJECTIVE
Leukotrienes are proinflammatory mediators. Ethanol inhibits the catabolism of both cysteinyl leukotrienes (leukotriene E(4) [LTE(4)] and N-acetyl-LTE(4)) and leukotriene B(4) (LTB(4)) in hepatocytes. We examined the metabolic derangement of leukotriene inactivation by ethanol in humans in vivo.


METHODS
LTE(4), N-acetyl-LTE(4), LTB(4), and 20-hydroxy-LTB(4) were quantified in urine samples from 16 patients with acute alcohol intoxication (mean blood ethanol, 75 mmol/L). In 9 healthy volunteers, urinary LTE(4) was determined before and after ethanol consumption (mean blood ethanol, 14 mmol/L).


RESULTS
The excretion of LTE(4) during alcohol intoxication was 286 compared with 36 nmol/mol creatinine in healthy subjects (P < 0.01); the corresponding values for N-acetyl-LTE(4) were 101 and 11 nmol/mol creatinine, respectively (P < 0.001). This excretion of cysteinyl leukotrienes decreased when the blood ethanol concentration returned to normal. LTB(4) and 20-hydroxy-LTB(4) were detectable only in patients with excessive blood ethanol concentrations (mean, 95 mmol/L). In healthy volunteers, LTE(4) excretion increased 3-5 hours after ethanol consumption (mean peak concentration of 1.5 nmol/L compared with 0.5 nmol/L for basal values; P < 0.005).


CONCLUSIONS
Ethanol at high concentration induces increased leukotriene excretion into urine. These changes are consistent with inhibition of leukotriene catabolism and inactivation induced by ethanol, as well as with a higher leukotriene formation caused by ethanol-induced endotoxemia.
Uemura
M
M
Deutsches Krebsforschungszentrum, Heidelberg, Germany. muemura@nmu-gw.naramed-u.ac.jp
Lehmann
W D
WD
Schneider
W
W
Seitz
H K
HK
Benner
A
A
Keppler-Hafkemeyer
A
A
Hafkemeyer
P
P
Kojima
H
H
Fujimoto
M
M
Tsujii
T
T
Fukui
H
H
Keppler
D
D
D000208:Acute Disease; D000328:Adult; D000428:Alcohol Drinking; D000435:Alcoholic Intoxication / Q000652:urine*; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood; D005260:Female; D006801:Humans; D007975:Leukotriene B4 / Q000652:urine*; D017999:Leukotriene E4 / Q000031:analogs & derivatives* / Q000652:urine; D008104:Liver Cirrhosis, Alcoholic / Q000175:diagnosis / Q000652:urine; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged
D002492:Central Nervous System Depressants; C059593:20-hydroxy-N-acetylleukotriene E4; D007975:Leukotriene B4; D000431:Ethanol; D017999:Leukotriene E4; C047630:N-acetylleukotriene E4; D003545:Cysteine