Chamulitrat W, Carnal J, Reed N M, Spitzer J J
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112-1393, USA.
Am J Physiol. 1998 Apr;274(4):G653-61. doi: 10.1152/ajpgi.1998.274.4.G653.
Endotoxemia is associated with alcoholic liver diseases; however, the effect of endotoxin on the oxidation of ethanol is not known. We tested the hypothesis that endotoxin treatment enhances hepatic ethanol radical production. The generation of free radicals by the liver was studied with spin-trapping technique utilizing the primary trap ethanol (0.8 g/kg) and the secondary trap alpha-(4-pyridyl-1-oxide)-N-t-butylnitrone (4-POBN; 500 mg/kg). Electron paramagnetic resonance (EPR) spectra of bile showed six-line signals, which were dependent on ethanol, indicating the trapping of ethanol-dependent radicals. Intravenous injections of Escherichia coli lipopolysaccharide (0.5 mg/kg) 0.5 h before 4-POBN plus ethanol treatment caused threefold increases of biliary radical adducts. EPR analyses of bile from [1-13C]ethanol-treated endotoxic rats showed the presence of species attributable to alpha-hydroxyethyl adduct, carbon-centered adducts, and ascorbate radical. The generation of endotoxin-induced increases of ethanol-dependent radicals was suppressed by 50% on GdCl3 (20 mg/kg i.v.) or desferrioxamine mesylate (1 g/kg i.p.) treatment. Our data show that in vivo endotoxin increases biliary ethanol-dependent free radical formation and that these processes are modulated by Kupffer cell activation and catalytic metals.
内毒素血症与酒精性肝病相关；然而，内毒素对乙醇氧化的影响尚不清楚。我们检验了内毒素治疗会增强肝脏乙醇自由基生成的假说。利用自旋捕获技术，以初级捕获剂乙醇（0.8 g/kg）和次级捕获剂α-(4-吡啶基-1-氧化物)-N-叔丁基硝酮（4-POBN；500 mg/kg）研究肝脏自由基的生成。胆汁的电子顺磁共振（EPR）光谱显示出六条线的信号，这些信号依赖于乙醇，表明捕获了依赖乙醇的自由基。在4-POBN加乙醇处理前0.5小时静脉注射大肠杆菌脂多糖（0.5 mg/kg），导致胆汁自由基加合物增加了三倍。对[1-13C]乙醇处理的内毒素血症大鼠的胆汁进行EPR分析，显示存在归因于α-羟乙基加合物、碳中心加合物和抗坏血酸自由基的物质。用氯化钆（20 mg/kg静脉注射）或去铁胺甲磺酸盐（1 g/kg腹腔注射）处理后，内毒素诱导的依赖乙醇的自由基生成增加被抑制了50%。我们的数据表明，体内内毒素会增加胆汁中依赖乙醇的自由基形成，并且这些过程受库普弗细胞活化和催化金属的调节。
