Cai Xiaopeng, Hua Shiyuan, Deng Jingwen, Du Zhen, Zhang Dongxiao, Liu Zhenfeng, Khan Nazif Ullah, Zhou Min, Chen Zhi
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou310003, China.
Institute of Translational Medicine, Zhejiang University, Hangzhou310009, China.
ACS Appl Mater Interfaces. 2022 Sep 28;14(38):42887-42903. doi: 10.1021/acsami.2c10506. Epub 2022 Sep 12.
Acetaminophen (APAP)-induced liver injury (AILI) is a common liver disease in clinical practice. Only one clinically approved drug, -acetylcysteine (NAC), for the treatment of AILI is available in clinics, but novel treatment strategies are still needed due to the complicated pathological changes of AILI and the side effects of NAC. Here, we found that astaxanthin (ASX) can prevent AILI through the Nrf2/HO-1 pathway. After treatment with ASX, there was a positive activation of the Nrf2/HO-1 pathway in AILI models both in vivo and in vitro accompanied by enhanced autophagy and reduced ferroptosis. In APAP-challenged L02 liver cells, ASX reduced autophagy and enhanced apoptosis of the cells. Furthermore, we developed ASX-loaded hollow mesoporous silica nanoparticles (HMSN@ASX) to improve the aqueous solubility of ASX and targeted delivery of ASX to the liver and then significantly improve the therapeutic effects. Taken together, we found that ASX can protect against AILI by activating the Nrf2/HO-1 pathway, which mainly affects oxidative stress, autophagy, and ferroptosis processes, and the HMSN@ASX nanosystem can target the liver to enhance the treatment efficiency of AILI.
对乙酰氨基酚（APAP）诱导的肝损伤（AILI）是临床实践中常见的肝脏疾病。临床上仅有一种经临床批准用于治疗AILI的药物——N-乙酰半胱氨酸（NAC），但由于AILI复杂的病理变化以及NAC的副作用，仍需要新的治疗策略。在此，我们发现虾青素（ASX）可通过Nrf2/HO-1途径预防AILI。用ASX处理后，AILI模型在体内和体外的Nrf2/HO-1途径均呈阳性激活，同时自噬增强，铁死亡减少。在APAP刺激的L02肝细胞中，ASX减少了细胞的自噬并增强了细胞凋亡。此外，我们开发了负载ASX的中空介孔二氧化硅纳米颗粒（HMSN@ASX）以提高ASX的水溶性并将ASX靶向递送至肝脏，进而显著提高治疗效果。综上所述，我们发现ASX可通过激活Nrf2/HO-1途径来预防AILI，该途径主要影响氧化应激、自噬和铁死亡过程，并且HMSN@ASX纳米系统可靶向肝脏以提高AILI的治疗效率。
