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

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 geneswere determined.Overall,the expression of most genes was downregulated by Intralipid?-based TPN(Gstpl,Gstml,3,6,Nqol,Ho-1,Mt-1,Gclc,Gclm,Cyp2d9,2f2,2b 10,and 3a11).Omegaven?showed similar results as Intralipid?except for preserving the expression of Gstml and Cyp3a11,and increasing Ho-1.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 Cyp3a11,suggesting another beneficial effect of Omegaven?in protecting liver functions.