Department of Nutrition, School of Public Health, Guangdong Medical University, Dongguan 523808, People's Republic of China.
Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, People's Republic of China.
Toxicol Sci. 2021 Dec 28;185(1):19-27. doi: 10.1093/toxsci/kfab123.
Coenzyme Q10 (CoQ10) which acts as an electron transporter in the mitochondrial respiratory chain has many beneficial effects on liver diseases. In our previous research, CoQ10 has been found to attenuate acetaminophen (APAP)-induced acute liver injury (ALI). However, whether CoQ10 administration is still effective at the late stage of APAP overdose is still unknown. In this study, we aimed to test CoQ10 efficacy at the late stage of APAP overdose. C57BL/6J mice were intraperitoneally treated with APAP to induce liver injury. CoQ10 (5 mg/kg) was given to mice at 16 h after APAP treatment. The results showed that while CoQ10 treatment at 16 h post-APAP overdose had no effects on the expression of ROS generated genes or scavenged genes, it still significantly decreased necrosis of hepatocytes following APAP-induced ALI. Moreover, CoQ10 increased MerTK+ macrophages accumulation in the APAP-overdose liver and inhibition of MerTK signaling partly abrogated the protective role of CoQ10 treatment on the hepatic necrosis. CoQ10 treatment also significantly enhanced hepatocytes proliferation as shown in the increased 5-bromodeoxyuridine incorporation in the APAP-intoxicated mice liver section. In addition, CoQ10 treatment increased hepatic Proliferating Cell Nuclear Antigen (PCNA) and Cyclin D1 expression and promoted activation of the β-catenin signaling in APAP-overdose mice. To conclude, these data provide evidence that CoQ10 treatment is still effective at the late stage of APAP-induced ALI and promotes resolution of necrosis and liver regeneration following ALI.
辅酶 Q10（CoQ10）作为线粒体呼吸链中的电子转运体，对肝脏疾病有许多有益的影响。在我们之前的研究中，发现 CoQ10 可以减轻对乙酰氨基酚（APAP）诱导的急性肝损伤（ALI）。然而，CoQ10 给药在 APAP 过量的晚期是否仍然有效尚不清楚。在这项研究中，我们旨在测试 CoQ10 在 APAP 过量晚期的疗效。C57BL/6J 小鼠经腹腔注射 APAP 诱导肝损伤。APAP 处理后 16 小时给予 CoQ10（5mg/kg）。结果表明，虽然 CoQ10 在 APAP 过量后 16 小时给药对 ROS 产生基因或清除基因的表达没有影响，但它仍然显著降低了 APAP 诱导的 ALI 后肝细胞的坏死。此外，CoQ10 增加了 APAP 过量肝脏中的 MerTK+巨噬细胞积聚，MerTK 信号通路的抑制部分阻断了 CoQ10 治疗对肝坏死的保护作用。CoQ10 治疗还显著增强了肝细胞的增殖，如在 APAP 中毒小鼠肝切片中 5-溴脱氧尿苷掺入的增加所示。此外，CoQ10 治疗增加了肝增殖细胞核抗原（PCNA）和细胞周期蛋白 D1 的表达，并促进了 APAP 过量小鼠中 β-连环蛋白信号的激活。总之，这些数据提供了证据表明，CoQ10 治疗在 APAP 诱导的 ALI 晚期仍然有效，并促进了 ALI 后坏死和肝再生的消退。
