Protective Effects of Facilitated Removal of Blood Alcohol and Acetaldehyde Against Liver Injury in Animal Models Fed Alcohol and Anti-HIV Drugs
Protective Effects of Facilitated Removal of Blood Alcohol and Acetaldehyde Against Liver Injury in Animal Models Fed Alcohol and Anti-HIV Drugs
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DOI：
10.1111/acer.14034
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发表时间：
2019-06-01
影响因子：
3.2
通讯作者：
Ji, Cheng
中科院分区：
文献类型：
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作者：
Han, Hui;He, Yuxin;Ji, Cheng
背景我们以前开发了酒精代谢酶纳米颗粒（ENP）。本研究旨在评估促进血液酒精和/或乙醛清除对抗艾滋病毒药物和酒精性肝损伤的保护作用。方法制备乙醇完全降解（ENP 1）和部分降解（ENP 2）的ENP，分别应用于急性和慢性酒精中毒小鼠，并与抗病毒药物利托那韦和洛匹那韦联用。检查肝脏病理以评估ENP的保护作用。结果在急性模型中，ENP 1和ENP 2在4小时内分别使血液酒精浓度（BAC）降低41%和32%，而在未使用ENP的对照组中，BAC仅降低15%。与对照组相比，ENP 2处理的酒精喂养小鼠的血液乙醛浓度（BADC）增加了39%。未观察到抗HIV药物对BAC或BADC的显著影响。血浆丙氨酸氨基转移酶（ALT）和肝脏TNF-α的表达都显着增加，在酒精喂养的小鼠，这是正常的ENP 1。在存在抗病毒药的情况下，ENP 1或ENP 2可部分降低ALT。在慢性模型中，炎症、脂肪肝和ALT增加，这些都被抗病毒药物恶化。ENP 1部分降低了BAC、BADC、ALT以及TNF-α、F4/80和IL-6的炎症标志物和ACC、LXR α和SREBP 1的脂肪生成因子的表达。ENP 2降低BAC，而对ALT、炎症或脂肪生成没有显著影响。抗病毒药物和酒精协同增加细胞器应激标志物CHOP、sXBP-1、ATF 6和GCP 60的表达。ENP 1减少BAC、CHOP和sXbp-1。然而，ENP 1对ATF 6或GCP 60没有影响。结论ENP清除血液中的酒精和乙醛可保护肝脏免受酒精损伤，但由于药物诱导的细胞器应激，这种保护作用在慢性酒精和抗病毒喂养中效果较差。
Background We previously developed enzyme nanoparticles (ENP) of alcohol metabolism. This study was to evaluate protective effects of facilitated removal of blood alcohol and/or acetaldehyde on anti-HIV drugs and alcohol-induced liver injuries. Methods ENP were prepared for degrading alcohol completely (ENP1) or partially into acetaldehyde (ENP2), which were applied to mice of acute binge or chronic-binge alcohol feeding in the presence of antivirals (ritonavir and lopinavir). Liver pathologies were examined to assess the protective effects of ENP. Results In the acute model, ENP1 and ENP2 reduced the blood alcohol concentration (BAC) by 41 and 32%, respectively, within 4 hr, whereas in control without ENP, BAC was reduced only by 15%. Blood acetaldehyde concentration (BADC) was increased by 39% in alcohol-fed mice treated with ENP2 comparing to control. No significant effects of the anti-HIV drugs on BAC or BADC were observed. Plasma alanine aminotransferase (ALT) and expression of liver TNF-alpha were both significantly increased in the alcohol-fed mice, which were normalized by ENP1. In the presence of the antivirals, ALT was partially reduced by ENP1 or ENP2. In the chronic model, inflammation, fatty liver, and ALT were increased, which were deteriorated by the antivirals. ENP1 partially reduced BAC, BADC, ALT, and expression of inflammation markers of TNF-alpha, F4/80, and IL-6 and lipogenic factors of ACC, LXR alpha, and SREBP1. ENP2 reduced BAC without significant effects on ALT, inflammation, or lipogenesis. Antivirals and alcohol synergistically increased expression of organelle stress markers of CHOP, sXBP-1, ATF6, and GCP60. ENP1 reduced BAC, CHOP, and sXbp-1. However, no effects of ENP1 were found on ATF6 or GCP60. Conclusions Removal of blood alcohol and acetaldehyde by the ENP protects the liver against alcoholic injuries, and the protection is less effective in chronic alcohol and antiviral feeding due to additional drug-induced organelle stresses.