Ferrucci-Da Silva Christina, Zhan Le, Shen Jianliang, Kong Bo, Campbell Michael J, Memon Naureen, Hegyi Thomas, Lu Lucy, Guo Grace L
Division of Neonatology, Department of Pediatrics, Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.
Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA.
Acta Pharm Sin B. 2020 Jan;10(1):153-158. doi: 10.1016/j.apsb.2019.10.012. Epub 2019 Nov 6.
Parenteral nutrition-associated liver disease (PNALD) is a liver dysfunction caused by various risk factors presented in patients receiving total parenteral nutrition (TPN). Omega-6 rich Intralipid® and omega-3 rich Omegaven® are two intravenous lipid emulsions used in TPN. TPN could affect the hepatic expression of genes in anti-oxidative stress, but it's unknown whether TPN affects genes in drug metabolism. In this study, either Intralipid®- or Omegaven®-based TPN was administered to mice and the expression of a cohort of genes involved in anti-oxidative stress or drug metabolism was analyzed, glutathione (GSH) levels were measured, and protein levels for two key drug metabolism genes were determined. Overall, the expression of most genes was downregulated by Intralipid®-based TPN ( and ). Omegaven® showed similar results as Intralipid® except for preserving the expression of and and increasing . Total GSH levels were decreased by Intralipid®, but increased by Omegaven®. CYP3A11 protein levels were increased by Omegaven®. In conclusion, TPN reduced the expression of many genes involved in anti-oxidative stress and drug metabolism in mice. However, Omegaven® preserved expression of , suggesting another beneficial effect of Omegaven® in protecting liver functions.
肠外营养相关肝病(PNALD)是一种由接受全肠外营养(TPN)的患者出现的各种危险因素引起的肝功能障碍。富含ω-6的英脱利匹特®和富含ω-3的奥米加维®是两种用于TPN的静脉脂质乳剂。TPN可能影响抗氧化应激相关基因的肝脏表达,但TPN是否影响药物代谢相关基因尚不清楚。在本研究中,给小鼠施用基于英脱利匹特®或奥米加维®的TPN,并分析一组参与抗氧化应激或药物代谢的基因的表达,测量谷胱甘肽(GSH)水平,并确定两个关键药物代谢基因的蛋白质水平。总体而言,基于英脱利匹特®的TPN使大多数基因的表达下调(和)。除了保留和的表达并增加外,奥米加维®显示出与英脱利匹特®相似的结果。英脱利匹特®使总GSH水平降低,但奥米加维®使其升高。奥米加维®使CYP3A11蛋白质水平升高。总之,TPN降低了小鼠中许多参与抗氧化应激和药物代谢的基因的表达。然而,奥米加维®保留了的表达,表明奥米加维®在保护肝功能方面的另一个有益作用。