Effects of total parenteral nutrition on drug metabolism gene expression in mice

• 来源期刊: 药学学报（英文版）
• 关键词: Total parenteral nutrition Glutathione Drug metabolism Liver Parenteral nutrition-associated liver disease
• 年，卷（期）: 2020,（1）
• 页码范围: 153-158
• 页数: 6页
• 语种: 英文

摘要

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（R） and omega-3 rich Omegaven（R） 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（R）-or Omegaven（R）-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（R）-based TPN (Gstpl,Gstml,3,6,Nqo1,Ho-1,Mt-1,Gclc,Gclm,Cyp2d9,2f2,2b10,and 3a11).Omegaven（R） showed similar results as Intralipid（R） except for preserving the expression of Gstml and Cyp3a11,and increasing Ho-1.Total GSH levels were decreased by lntralipid（R）,but increased by Omegaven（R）.CYP3A11 protein levels were increased by Omegaven（R）.In conclusion,TPN reduced the expression of many genes involved in anti-oxidative stress and drug metabolism in mice.However,Omegaven（R） preserved expression of Cyp3a11,suggesting another beneficial effect of Omegaven（R） in protecting liver functions.