辅酶Q10(CoQ10)是线粒体中电子传输链的关键辅因子,已显示出对肝脏疾病的许多有益作用。然而,辅酶Q10对对乙酰氨基酚(APAP)诱导的肝损伤的保护作用机制尚不清楚,目前尚不清楚。在这项研究中,我们进一步研究了辅酶Q10对APAP过量肝损伤的治疗作用。用APAP腹膜内处理C57BL / 6 J小鼠,以诱导肝损伤。在APAP处理后1.5小时,将CoQ10(5 mg / kg)给予小鼠。结果表明,在APAP诱导的肝毒性过程中,肝CoQ10水平降低,且血清ALT升高。辅酶Q10的治疗可显着改善APAP引起的肝损伤。此外,辅酶Q10处理可降低APAP过量小鼠的ROS水平并促进其抗氧化相关基因的表达。重要的是,结果表明,即使辅酶Q10对mtDNA拷贝数和与线粒体生物发生有关的基因的表达没有影响,它也显着改善了线粒体复合体的I和V活性,并促进了APAP过量小鼠的线粒体吞噬作用。为了进一步验证在CoQ10介导的体内改善肝损伤中的线粒体作用,我们在APAP治疗前1小时给过量服用APAP的小鼠施用了氯喹,发现氯喹治疗功能上取消了CoQ10对APAP过量小鼠的保护作用。总而言之,这项研究提供了CoQ10激活线粒体以防止APAP诱导的肝损伤的证据。因此,辅酶Q10可能代表了预防和治疗药物性肝损伤的一种新的治疗选择。结果表明,即使辅酶Q10对mtDNA拷贝数和与线粒体生物发生有关的基因的表达没有影响,它也显着改善了线粒体复合体的I和V活性,并促进了APAP过量小鼠的线粒体吞噬作用。为了进一步验证在CoQ10介导的体内改善肝损伤中的线粒体作用,我们在APAP治疗前1小时给过量服用APAP的小鼠施用了氯喹,发现氯喹治疗在功能上废除了CoQ10对APAP过量小鼠的保护作用。总而言之,这项研究提供了CoQ10激活线粒体以防止APAP诱导的肝损伤的证据。因此,辅酶Q10可能代表了一种预防和治疗药物性肝损伤的新型治疗选择。结果表明,即使辅酶Q10对mtDNA拷贝数和与线粒体生物发生有关的基因的表达没有影响,它也显着改善了线粒体复合体的I和V活性,并促进了APAP过量小鼠的线粒体吞噬作用。为了进一步验证在CoQ10介导的体内改善肝损伤中的线粒体作用,我们在APAP治疗前1小时给过量服用APAP的小鼠施用了氯喹,发现氯喹治疗在功能上废除了CoQ10对APAP过量小鼠的保护作用。总而言之,这项研究提供了CoQ10激活线粒体以防止APAP诱导的肝损伤的证据。因此,辅酶Q10可能代表了一种预防和治疗药物性肝损伤的新型治疗选择。
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CoQ10 protects against acetaminophen-induced liver injury by enhancing mitophagy
Coenzyme Q10 (CoQ10), which is a key cofactor of the electron transport chain in the mitochondria has shown many beneficial effects on liver diseases. However, the mechanisms of CoQ10 protective role on the acetaminophen (APAP)-induced liver injury are elusive and unclear. In this study, we further investigated the CoQ10 therapeutic effects on APAP-overdose liver injury. C57BL/6 J mice were intraperitoneally treated with APAP to induce liver injury. CoQ10 (5 mg/kg) was given to mice at 1.5 h after APAP treatment. The results showed that hepatic CoQ10 levels were decreased during the APAP-induced hepatotoxicity and preceded serum ALT elevation. Treatment of CoQ10 significantly improved the liver injury induced by APAP. Moreover, CoQ10 treatment decreased the ROS levels and promoted the antioxidative related gene expression in APAP overdose mice. Importantly, results showed that even though CoQ10 had no effects on the mtDNA copy number and the expression of genes related to mitochondrial biogenesis, it significantly improved the mitochondrial complex I and V activities and promoted the mitophagy in APAP-overdose mice. To further authenticate mitophagy role in CoQ10-mediated improved liver injury in vivo, we administrated APAP-overdose mice with chloroquine 1 h prior to APAP treatment and found that chloroquine treatment functionally abrogated the CoQ10 protective role on APAP overdose mice. To conclude, this study provides evidence that CoQ10 activates mitophagy to protect against APAP-induced liver injury. Therefore, CoQ10 may represent a novel therapeutic option for the prevention and treatment of drug-induced liver injury.