Uemura M, Lehmann W D, Schneider W, Seitz H K, Benner A, Keppler-Hafkemeyer A, Hafkemeyer P, Kojima H, Fujimoto M, Tsujii T, Fukui H, Keppler D
Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Gastroenterology. 2000 Jun;118(6):1140-8. doi: 10.1016/s0016-5085(00)70367-2.
BACKGROUND & AIMS: 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.
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).
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).
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.
白三烯是促炎介质。乙醇可抑制肝细胞中半胱氨酰白三烯（白三烯E4 [LTE4]和N-乙酰-LTE4）以及白三烯B4（LTB4）的分解代谢。我们在人体中研究了乙醇对体内白三烯失活的代谢紊乱情况。
对16例急性酒精中毒患者（平均血液乙醇浓度为75 mmol/L）的尿液样本中的LTE4、N-乙酰-LTE4、LTB4和20-羟基-LTB4进行定量分析。在9名健康志愿者中，测定饮酒前后（平均血液乙醇浓度为14 mmol/L）尿液中的LTE4。
酒精中毒期间LTE4的排泄量为286，而健康受试者为36 nmol/mol肌酐（P < 0.01）；N-乙酰-LTE4的相应值分别为101和11 nmol/mol肌酐（P < 0.001）。当血液乙醇浓度恢复正常时，半胱氨酰白三烯的排泄量减少。仅在血液乙醇浓度过高（平均95 mmol/L）的患者中可检测到LTB4和20-羟基-LTB4。在健康志愿者中，饮酒后3 - 5小时LTE4排泄量增加（平均峰值浓度为1.5 nmol/L，基础值为0.5 nmol/L；P < 0.005）。
高浓度乙醇会导致尿液中白三烯排泄增加。这些变化与乙醇诱导的白三烯分解代谢和失活受抑制一致，也与乙醇诱导的内毒素血症导致白三烯生成增加相符。
