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

Acta Pharmaceutica Sinica B 2020年第1期10卷 153-158页

作者： Christina Ferrucci-Da Silva Le Zhan Jianliang Shen Bo Kong michael jcampbell Naureen Memon Thomas Hegyi Lucy Lu Grace L.Guo Division of Neonatology Department of PediatricsRobert Wood Johnson Medical SchoolNew BrunswickNJ 08901USA Rutgers Cancer Institute of New Jersey New BrunswickNJ 08901USA Department of Molecular Biology and Biochemistry Rutgers UniversityPiscatawayNJ 08854USA Department of Pharmacology and Toxicology School of PharmacyRutgers UniversityPiscatawayNJ 08854USA MidAtlantic Neonatology Associates MorristownNJ 07960USA School of Pharmacy University of PittsburghPittsburghPA 15260USA Environmental and Occupational Health Institute Rutgers UniversityPiscatawayNJ 08854USA VA NJ Health Care Systems East OrangeNJ 07018USA Monmouth Medical Center in Long Branch NJ 07740USA

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 *** could affect the hepatic expression of genes in anti-oxidative stress,but it’s unknown whether TPN affects genes in drug *** 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 ***,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 *** 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 ***,Omegaven?preserved expression of Cyp3a11,suggesting another beneficial effect of Omegaven?in protecting liver functions.

关键词： Total parenteral nutrition Glutathione Drug metabolism Liver Parenteral nutritionassociated liver disease

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