PMID- 24281836
OWN - NLM
STAT- MEDLINE
DCOM- 20141028
LR  - 20140306
IS  - 1521-009X (Electronic)
IS  - 0090-9556 (Linking)
VI  - 42
IP  - 4
DP  - 2014 Apr
TI  - Malaria infection alters the expression of hepatobiliary and placental drug 
      transporters in pregnant mice.
PG  - 603-10
LID - 10.1124/dmd.113.053983 [doi]
AB  - Preventing and treating malaria in pregnancy is a global health priority. However 
      little is known regarding the impact of malaria infection on the maternal and 
      fetal disposition of pharmaceuticals and other xenobiotics. Our objective was to 
      characterize expression of key determinants of drug-disposition in maternal and 
      fetal tissues in a validated murine model of experimental placental malaria. 
      Balb/c mice were infected with Plasmodium berghei at mid gestation [gestational 
      day (GD) 13] and maternal, placental, and fetal tissues were collected at GD19. 
      Expression of key ABC drug transporters and Cyp3a11 was examined by quantitative 
      polymerase chain reaction. Western blotting was used to examine the protein 
      expression of multidrug resistance protein 1 (MDR1, ABCB1). Compared with 
      controls, placental mRNA expression of Abcb1a, Abcb1b, Abcc1, Abcc2, Abcc3, and 
      Abcg2 were significantly downregulated in the malaria-infected group (P < 0.05), 
      as was placental MDR1 protein (P < 0.05). Significantly decreased hepatic 
      expression of Abcc2, Abcg2, and Abcb11 and significantly increased expression of 
      Abcb1b, Abcc1, and Abcc3 were seen in malaria-infected dams (P < 0.05) in 
      comparison with uninfected controls. The expression of Abcb1a and Abcg2 was 
      significantly decreased in fetal liver of infected dams, whereas levels of Abcb1b 
      were increased (P < 0.05). Maternal and fetal hepatic expression of Cyp3a11 was 
      significantly downregulated in the malaria group (P < 0.05). Together, 
      malaria-induced alterations in the expression of transporters and 
      drug-metabolizing enzymes in maternal and fetal tissues may alter the disposition 
      of endogenous and therapeutic substrates, potentially impacting maternal and 
      fetal outcomes.
FAU - Cressman, Alex M
AU  - Cressman AM
AD  - Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University 
      of Toronto, Toronto, Ontario, Canada (A.M.C., M.P.-M.); and Sandra Rotman Centre 
      for Global Health, University Health Network-Toronto General Hospital, Toronto, 
      Ontario, Canada (C.R.M., K.S., K.C.K.).
FAU - McDonald, Chloe R
AU  - McDonald CR
FAU - Silver, Karlee
AU  - Silver K
FAU - Kain, Kevin C
AU  - Kain KC
FAU - Piquette-Miller, Micheline
AU  - Piquette-Miller M
LA  - eng
GR  - 13721/Canadian Institutes of Health Research/Canada
GR  - 57688/Canadian Institutes of Health Research/Canada
GR  - MOP-115160/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131126
PL  - United States
TA  - Drug Metab Dispos
JT  - Drug metabolism and disposition: the biological fate of chemicals
JID - 9421550
RN  - 0 (Bile Acids and Salts)
RN  - 0 (Carrier Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Pharmaceutical Preparations)
RN  - EC 1.14.14.1 (Cyp3a11 protein, mouse)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP3A)
SB  - IM
MH  - Animals
MH  - Bile Acids and Salts/blood
MH  - Biological Transport
MH  - Carrier Proteins/*genetics/metabolism
MH  - Cytochrome P-450 CYP3A/genetics/metabolism
MH  - Disease Models, Animal
MH  - Female
MH  - Liver/embryology/*metabolism
MH  - Malaria/*metabolism/parasitology
MH  - Membrane Proteins/genetics/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Oxidative Stress
MH  - Pharmaceutical Preparations/*metabolism
MH  - Placenta/*metabolism
MH  - Plasmodium berghei/pathogenicity
MH  - Pregnancy
MH  - Pregnancy Complications, Parasitic/*metabolism/parasitology
MH  - Tissue Distribution
EDAT- 2013/11/28 06:00
MHDA- 2014/10/29 06:00
CRDT- 2013/11/28 06:00
PHST- 2013/11/28 06:00 [entrez]
PHST- 2013/11/28 06:00 [pubmed]
PHST- 2014/10/29 06:00 [medline]
AID - dmd.113.053983 [pii]
AID - 10.1124/dmd.113.053983 [doi]
PST - ppublish
SO  - Drug Metab Dispos. 2014 Apr;42(4):603-10. doi: 10.1124/dmd.113.053983. Epub 2013 
      Nov 26.