Spermidine Prevents Ethanol and Lipopolysaccharide-Induced Hepatic Injury in Mice.
Spermidine Prevents Ethanol and Lipopolysaccharide-Induced Hepatic Injury in Mice.
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DOI：
10.3390/molecules26061786
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发表时间：
2021-03-22
期刊：
影响因子：
--
通讯作者：
Tuma PL
中科院分区：
文献类型：
--
作者：
Adhikari R;Shah R;Reyes-Gordillo K;Arellanes-Robledo J;Cheng Y;Ibrahim J;Tuma PL
迄今为止，尽管酒精性肝病在世界范围内流行，但仍没有有效的治疗方法。由于酒精消费与氧化应激诱导的肝损伤和促炎反应有关，因此天然存在的抗氧化剂和/或抗炎剂可能是潜在的治疗剂。亚精胺是一种丰富的，普遍存在的多胺，已被发现显示出强大的抗氧化剂和抗炎特性。为了进一步研究亚精胺是否是一种有效的干预酒精诱导的肝脏疾病，我们研究了它的肝保护特性，使用两次打击，慢性乙醇和急性脂多糖（LPS）诱导的小鼠肝损伤模型。我们确定，亚精胺管理防止乙醇和LPS诱导的肝损伤的增加，使用血浆ALT作为读数。此外，对照组和处理组动物组织的组织学分析显示，在用亚精胺额外处理的小鼠中，与乙醇和LPS处理相关的病理学得到预防。正如所预测的，亚精胺也防止乙醇和LPS诱导的氧化应激，通过降低活性氧（ROS）和脂质过氧化的水平。我们进一步确定亚精胺处理通过阻断抑制蛋白I κ B的磷酸化来阻止核因子κ B（NF κ B）的核转位，从而阻止促炎细胞因子的表达。最后，通过测量已知肝星状细胞活化标志物的表达和监测胶原沉积，我们观察到亚精胺也可以预防酒精和LPS诱导的肝纤维化。总之，我们的研究结果表明，亚精胺是一种抗氧化剂，从而赋予与酒精性肝损伤相关的抗炎和抗纤维化作用。
To date, there is no effective treatment for alcoholic liver disease, despite its prevalence world-wide. Because alcohol consumption is associated with oxidative stress-induced liver injury and pro-inflammatory responses, naturally occurring antioxidants and/or anti-inflammatories may be potential therapeutics. Spermidine is an abundant, ubiquitous polyamine that has been found to display strong antioxidant and anti-inflammatory properties. To further investigate whether spermidine is an effective intervention for alcohol-induced liver disease, we examined its hepatoprotective properties using a two-hit, chronic ethanol and acute lipopolysaccharide (LPS)-induced mouse model of liver injury. We determined that spermidine administration prevented ethanol and LPS-induced increases in liver injury using plasma ALT as a readout. Furthermore, histological analysis of tissue from control and treated animals revealed that the pathology associated with ethanol and LPS treatment was prevented in mice additionally treated with spermidine. As predicted, spermidine also prevented ethanol and LPS-induced oxidative stress by decreasing the levels of both reactive oxygen species (ROS) and lipid peroxidation. We further determined that spermidine treatment prevented the nuclear translocation of nuclear factor κB (NFκB) by blocking the phosphorylation of the inhibitory protein, IκB, thereby preventing expression of pro-inflammatory cytokines. Finally, by measuring expression of known markers of hepatic stellate cell activation and monitoring collagen deposition, we observed that spermidine also prevented alcohol and LPS-induced hepatic fibrosis. Together, our results indicate that spermidine is an antioxidant thereby conferring anti-inflammatory and anti-fibrotic effects associated with alcoholic liver injury.
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DOI：
10.1002/hep.23009
发表时间：
2009-08
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Rao R
通讯作者：
Rao R
影响因子：
11.2
作者：
Yue F;Li W;Zou J;Jiang X;Xu G;Huang H;Liu L
通讯作者：
Liu L
影响因子：
4.6
作者：
Okumura, Shinya;Teratani, Takumi;Uemoto, Shinji
通讯作者：
Uemoto, Shinji
影响因子：
14.8
作者：
通讯作者：
--
DOI：
10.1016/j.bbagen.2007.02.004
发表时间：
2007-06-01
影响因子：
3
作者：
Reyes-Gordillo, Karina;Segovia, Jose;Muriel, Pablo
通讯作者：
Muriel, Pablo