Oral administration of tributyrin increases concentration of butyrate in the portal vein and prevents lipopolysaccharide-induced liver injury in rats
Oral administration of tributyrin increases concentration of butyrate in the portal vein and prevents lipopolysaccharide-induced liver injury in rats
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DOI：
10.1016/j.clnu.2010.09.012
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发表时间：
2011-04-01
影响因子：
6.3
通讯作者：
Usami, Yu
中科院分区：
文献类型：
--
作者：
Miyoshi, Makoto;Sakaki, Hiroe;Usami, Yu
背景和目标：短链脂肪酸，特别是丁酸，具有多种生物活性，包括抑制肿瘤坏死因子（TNF）-α。分泌，通过减弱核因子-κ B（NF-κ B）活化。本研究旨在探讨丁酸酯前体药物三丁酸甘油酯对脂多糖（LPS）诱导的大鼠肝损伤的保护作用。LPS和三丁酸甘油酯/LPS（在LPS前1小时用三丁酸甘油酯处理）。丁酸和TNF-α的血浆水平，TNF-α，NF-κ B，Toll样受体（TLR）2，和TLR4 mRNA在肝脏中的表达，血液生化试验，和肝脏的组织病理学分析performed.Results：口服三丁酸甘油酯增加血浆丁酸水平在门静脉中的2.4 mM在1小时和0.7 mM在2.5小时。三丁酸甘油酯减弱与LPS注射相关的NF-κ B活化和肝组织损伤。三丁酸甘油酯/LPS组中TNF-α水平和肝脏TLR2 mRNA表达的增加较低。我们认为，这项研究提供了第一个证据表明，口服三丁酸甘油酯增加丁酸水平在肝门静脉系统和减轻肝损伤和随后的炎症responses.Conclusion：口服三丁酸甘油酯增加血浆丁酸在门静脉和减轻内毒素血症大鼠肝损伤。(C)2010年爱思唯尔有限公司和欧洲临床营养与代谢学会。All rights reserved.
Background & aims: Short-chain fatty acids, especially butyrate, have various biological activities including inhibition of tumor necrosis factor (TNF)-alpha. secretion, via attenuation of nuclear factor-kappa B (NF-kappa B) activation. Here, we evaluated the protective effect of oral administration of tributyrin, a prodrug of butyrate, on lipopolysaccharide (LPS)-induced liver injury in rats.Methods: Rats were divided into four groups: normal control, tributyrin. LPS, and tributyrin/LPS (treated with tributyrin 1 h before LPS). Plasma levels of butyrate and TNF-alpha, expression of TNF-alpha, NF-kappa B, Toll-like receptor (TLR) 2, and TLR4 mRNA in liver, blood biochemical tests, and histopathological analysis of liver were performed.Results: Oral tributyrin increased plasma butyrate level in the portal vein to 2.4 mM at 1 h and 0.7 mM at 2.5 h. Tributyrin attenuated NF-kappa B activation and liver tissue injury associated with LPS injection. The increases in TNF-alpha level, and hepatic TLR2 mRNA expression were lower in the tributyrin/LPS group. We believe that this study provides the first evidence that orally administered tributyrin increases butyrate level in the hepato-portal system and attenuates liver injury and subsequent inflammatory responses.Conclusion: Oral tributyrin increased plasma butyrate in the portal vein and attenuated liver injury in endotoxemic rats. (C) 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.