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Effect of Oral Tributyrin Treatment on Lipid Mediator Profiles in Endotoxin-Induced Hepatic Injury

机译:口服Tributyrin治疗对内毒素诱导的肝损伤脂凝固蛋白谱的影响

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摘要

Eicosanoid modulation by butyrate has been reported in various cells and conditions. Recently, comprehensive analyses of lipid mediators using liquid chromatography/tandem mass spectrometry has been reported. We hypothesized that tributyrin, a prodrug of butyrate, may attenuate LPS-induced liver injury in rats by suppressing the production of pro-inflammatory lipid mediators and/or by inducing anti-inflammatory specialized proresolving mediators. To test this, groups of Wistar rats were orally administered tributyrin (1 g/kg body weight) or vehicle 1 h before intraperitoneal injection of LPS. The livers were collected at 0, 1.5, 6, and 24 h later and analyzed: lipid mediators were profiled by liquid chromatography/tandem mass spectrometry; expression of cyclooxygenase-2, 5-lipoxygenase (LOX), 12/15-LOX, and leukotriene (LT) A4 hydrolase, and nuclear translocation of 5-LOX were evaluated by western blot analysis; and induction of liver injury was assessed by immunostaining for 8-hydroxy-2′-deoxyguanosine, an indicator of oxidative DNA damage. We found that tributyrin treatment attenuated LPS-induced production of pro-inflammatory LTB4 (p < 0.05) and decreased oxidative stress levels in the liver. Tributyrin also attenuated the nuclear translocation of 5-LOX in response to LPS, suggesting a possible mechanism for the LTB4 reduction. LPS-induced changes in other lipid mediators were not significantly affected by tributyrin treatment up to 24 h after LPS injection. Our results suggest that oral tributyrin administration protects against endotoxemia-associated liver damage by reducing production of the pro-inflammatory eicosanoid LTB4.
机译:在各种细胞和条件下报道了丁酸盐的逐渐调节。最近,据报道了使用液相色谱/串联质谱法的脂质介质综合分析。我们假设通过抑制促炎脂介质和/或通过诱导抗炎专业的预介质介质,丁酸丁酸的前药,丁酸盐的前药可以衰减LPS诱导的肝损伤。为了测试这一点,在腹膜内注射LPS之前,口服施用呋喃酮大鼠的杂烩蛋白(1g / kg体重)或载体1小时。以0,1.5,6和24小时收集肝脏,并分析:通过液相色谱/串联质谱法分析脂质介质;通过Wesphere印迹分析评估环氧氢止酶-2,5-脂氧基酶-2,5-脂氧合酶(LOX),12/15-LOX和白酮(LOX)A4水解酶的核转位,以及5-LOX的核转位;通过对8-羟基-2'-脱氧核苷酸的免疫染色来评估肝损伤的诱导,氧化DNA损伤的指示。我们发现,Tributyrin治疗减毒了LPS诱导的促炎LTB4(P <0.05)并降低了肝脏中的氧化应激水平。 Tributyrin还响应LPS抑制了5-LOX的核转位,表明LTB4减少的可能机制。在LPS注射后,LPS诱导的其他脂质介质的变化在Tributyrin治疗中没有显着影响24小时。我们的研究结果表明,通过减少促炎瘦糖蛋白LTB4的生产,口服呋喃林给予防止内毒素相关的肝损伤。

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