Medium-chain triglycerides inhibit free radical formation and TNF-α production in rats given enteral ethanol
Medium-chain triglycerides inhibit free radical formation and TNF-α production in rats given enteral ethanol
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DOI：
10.1152/ajpgi.2000.278.3.g467
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发表时间：
2000-03-01
影响因子：
4.5
通讯作者：
Thurman, RG
中科院分区：
文献类型：
--
作者：
Kono, H;Enomoto, N;Thurman, RG
这项研究确定了自由基形成的肝脏，肿瘤坏死因子（TNF）-α生产的分离枯否细胞，血浆内毒素是否受饮食饱和脂肪。大鼠经肠内给予乙醇和玉米油（E-CO）或中链甘油三酯（E-MCT），对照组大鼠给予玉米油（C-CO）或中链甘油三酯（C-MCT），持续2周。E-CO大鼠出现中度脂肪浸润和轻度炎症;然而，E-MCT可预防肝损伤。血清天冬氨酸转氨酶水平、肠道通透性和血浆内毒素水平在E-CO组加倍，但在E-MCT组减弱至50%。在E-CO大鼠的Kupffer细胞中，脂多糖（LPS）以剂量依赖的方式升高细胞内钙。在来自E-MCT大鼠的细胞中，在所有浓度的LPS下，增加被钝化了40-50%。LPS诱导的库普弗细胞TNF-α产生增加具有剂量依赖性，MCT使其减弱40%。E-CO增加了自由基加合物，并通过MCT减少了50%。MCT通过抑制内毒素介导的枯否细胞活化来抑制自由基形成和TNF-α产生，从而部分预防早期酒精诱导的肝损伤。
This study determined whether free radical formation by the liver, tumor necrosis factor (TNF)-alpha production by isolated Kupffer cells, and plasma endotoxin are affected by dietary saturated fat. Rats were fed enteral ethanol and corn oil (E-CO) or medium-chain triglycerides (E-MCT) and control rats received corn oil (C-CO) or medium-chain triglycerides (C-MCT) for 2 wk. E-CO rats developed moderate fatty infiltration and slight inflammation; however, E-MCT prevented liver injury. Serum aspartate aminotransferase levels, gut permeability, and plasma endotoxin doubled with E-CO but were blunted similar to 50% with E-MCT. In Kupffer cells from E-CO rats, intracellular calcium was elevated by lipopolysaccharide (LPS) in a dose-dependent manner. In cells from E-MCT rats, increases were blunted by similar to 40-50% at all concentrations of LPS. The LPS-induced increase in TNF-alpha production by Kupffer cells was dose dependent and was blunted by 40% by MCT. E-CO increased radical adducts and was reduced similar to 50% by MCT. MCT prevent early alcohol-induced liver injury, in part, by inhibition of free radical formation and TNF-alpha production by inhibition of endotoxin-mediated activation of Kupffer cells.