Selvaraj Vellaisamy, Nepal Niraj, Rogers Steven, Manne Nandini D P K, Arvapalli Ravikumar, Rice Kevin M, Asano Shinichi, Fankhanel Erin, Ma Jane J, Shokuhfar Tolou, Maheshwari Mani, Blough Eric R
Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA.
Health Effects Laboratory Division, NIOSH, Morgantown, WV, USA.
Biomaterials. 2015 Aug;59:160-71. doi: 10.1016/j.biomaterials.2015.04.025. Epub 2015 May 15.
Sepsis is a life threatening disease that is associated with high mortality. Existing treatments have failed to improve survivability in septic patients. The purpose of this present study is to evaluate whether cerium oxide nanoparticles (CeO2NPs) can prevent lipopolysaccharide (LPS) induced severe sepsis mortality by preventing hepatic dysfunction in male Sprague Dawley rats. Administration of a single dose (0.5 mg/kg) of CeO2NPs intravenously to septic rats significantly improved survival rates and functioned to restore body temperature, respiratory rate and blood pressure towards baseline. Treatment-induced increases in animal survivability were associated with decreased hepatic damage along with reductions in serum cytokines/chemokines, and diminished inflammatory related signaling. Kupffer cells and macrophage cells exposed to CeO2NPs exhibited decreases in LPS-induced cytokine release (TNF-α, IL-1β, IL-6, HMGB1) which were associated with diminished cellular ROS, reduced levels of nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), and decreased nuclear factor-kappa light chain enhancer of activated B cells (NF-kB) transcriptional activity. The findings of this study indicate that CeO2NPs may be useful as a therapeutic agent for sepsis.
脓毒症是一种危及生命的疾病，死亡率很高。现有的治疗方法未能提高脓毒症患者的生存率。本研究的目的是评估氧化铈纳米颗粒（CeO2NPs）是否能通过预防雄性Sprague Dawley大鼠的肝功能障碍来预防脂多糖（LPS）诱导的严重脓毒症死亡。向脓毒症大鼠静脉注射单剂量（0.5 mg/kg）的CeO2NPs可显著提高生存率，并使体温、呼吸频率和血压恢复至基线水平。治疗引起的动物生存率提高与肝损伤减轻、血清细胞因子/趋化因子减少以及炎症相关信号减弱有关。暴露于CeO2NPs的库普弗细胞和巨噬细胞表现出LPS诱导的细胞因子释放（TNF-α、IL-1β、IL-6、HMGB1）减少，这与细胞内活性氧减少、一氧化氮合酶（iNOS）和环氧合酶2（COX-2）水平降低以及活化B细胞核因子κB（NF-κB）转录活性降低有关。本研究结果表明，CeO2NPs可能作为脓毒症的治疗药物。
