Selenium nanoparticles(SeNPs)have been demonstrated potential for use in diseases associated with oxidative stress.Functionalized SeNPs with lower toxicity and higher biocompatibility could bring better therapeutic activity and clinical application value.Herein,this work was conducted to investigate the protectiveeffect of Pleurotus tuber-regium polysaccharide-protein complex funtionnalized SeNPs(PTR-SeNPs)against acetaminophen(APAP)-induced oxidative injure in HepG2 cells and C57BL/6J mouse liver.Further elucidation of the underlying molecular mechanism,in particular their modulation of Nrf2 signaling pathway was also performed.The results showed that PTR-SeNPs could significantly ameliorate APAP-induced oxidative injury as evidenced by a range of biochemical analysis,histopathological examination and immunoblotting study.PTR-SeNPs could hosphorylate and activate PKCδ,depress Keap1,and increase nuclear accumulation of Nrf2,resulting in upregulation of GCLC,GCLM,HO-1 and NQO-1expression.Besides,PTR-SeNPs suppressed the biotransformation of APAP to generate intracellular ROS through {102} 2{104}1 inhibition,restoring the mitochondrial morphology.Furthermore,the protectiveeffect of PTR-SeNPs against APAP induced hepatotoxicity was weakened as Nrf2 was depleted in vivo,indicating the pivotal role of Nrf2 signaling pathway in PTR-SeNPs mediated hepatoprotectiveefficacy.Being a potential hepatic protectant,PTR-SeNPs could serve as a new source of selenium supplement for health-promoting and biomedical applications.
Si ZouYetao GongXiujie LiYanbin WuJinzhong WuJianguo WuKa-Hing Wong
Alcoholic liver disease(ALD)results from continuous and heavy alcohol consumption.The current treatment strategy for ALD is based on alcohol withdrawal coupled with antioxidant drug intervention,which is a long process with poor efficacy and low patient compliance.Alcohol-induced {19}2{21}1 upregulation has been demonstrated as a key regulator of ALD,but {19}2{21}1 knockdown in humans was impractical,and pharmacological inhibition of {19}2{21}1 by a clinically relevant approach for treating ALD was not shown.In this study,we developed a RNAi therapeutics delivered by lipid nanoparticle,and treated mice fed on Lieber-DeCarli ethanol liquid diet weekly for up to 12 weeks.This RNAi-based inhibition of Cyp2e1expression reduced reactive oxygen species and oxidative stress in mouse livers,and contributed to improved ALD symptoms in mice.The liver fat accumulation,hepatocyte inflammation,and fibrosis were reduced in ALD models.Therefore,this study suggested the feasibility of RNAi targeting to {19}2{21}1 as a potential therapeutic tool to the development of ALD.
Yalan WangQiubing ChenShuang WuXinyu SunRunting YinZhen OuyangHao YinYuan Wei
