Effects of total parenteral nutrition on drug metabolism gene expression in mice.
10.1016/j.apsb.2019.10.012
- Author:
Christina FERRUCCI-DA SILVA
1
;
Le ZHAN
2
;
Jianliang SHEN
3
;
Bo KONG
4
;
Michael J CAMPBELL
4
;
Naureen MEMON
5
;
Thomas HEGYI
1
;
Lucy LU
6
;
Grace L GUO
4
Author Information
1. Division of Neonatology, Department of Pediatrics, Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.
2. Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA.
3. Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854, USA.
4. Department of Pharmacology and Toxicology, School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA.
5. MidAtlantic Neonatology Associates, Morristown, NJ 07960, USA.
6. School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15260, USA.
- Publication Type:Journal Article
- Keywords:
CYP450, cytochrome p450;
Drug metabolism;
FAs, fatty acids;
GADPH, glyceraldehyde 3-phosphate dehydrogenase;
GSH, glutathione;
GSSG, GSH/glutathione disulfide;
Gclc: glutamate-cysteine ligase catalytic subunit, Gclm: glutamate-cysteine ligase modifier subunit;
Glutathione;
Gpx3, glutathione peroxidase 3;
Gstm1, glutathione S-transferase, mu 1;
Gstm3, glutathione S-transferase, mu 3;
Gstm6, glutathione S-transferase, mu 6;
Gstp1, glutathione S-transferase, pi 1;
Ho-1, heme oxygenase 1;
Liver;
Mt-1, metallothionein 1;
NQO1, NAD(P)H:quinone acceptor oxidoreductase 1;
PNALD, parenteral nutrition-associated liver disease;
Parenteral nutrition-associated liver disease;
ROS, reactive oxygen species;
TPN, total parenteral nutrition;
Total parenteral nutrition
- From:
Acta Pharmaceutica Sinica B
2020;10(1):153-158
- CountryChina
- Language:English
-
Abstract:
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.
