PMID- 17399699
OWN - NLM
STAT- MEDLINE
DCOM- 20070726
LR  - 20181201
IS  - 0014-2999 (Print)
IS  - 0014-2999 (Linking)
VI  - 565
IP  - 1-3
DP  - 2007 Jun 22
TI  - Effects of lipopolysaccharide on intestinal P-glycoprotein expression and 
      activity.
PG  - 220-4
AB  - It is well known that pharmacokinetics is often altered by changing the 
      expression and activity of P-glycoprotein during sepsis. However, there have been 
      few reports about expression and activity of P-glycoprotein in the small 
      intestine during sepsis. We examined the levels of intestinal P-glycoprotein 
      expression and activity using a rat sepsis model induced by lipopolysaccharide 
      (LPS, from Escherichia coli). LPS was administered to male Wistar/ST rats 
      intraperitonealy (i.p.) at 5 mg/kg. The small intestine was excised before and 1, 
      3 and 7 days after LPS administration, and the intestinal P-glycoprotein 
      expression was determined using Western blot analysis. The activity of 
      P-glycoprotein was evaluated by measuring the efflux of rhodamine-123 (Rho123) in 
      rats using an in situ single perfusion method. The changes of permeability via 
      the paracellular route were evaluated by measuring the amount of fluorescein 
      isothicyanate-dextran 4400 (FD-4) in a similar way. On Day 1 after LPS 
      administration, both the level of P-glycoprotein expression and the total amount 
      of Rho123 excreted into the intestinal lumen decreased significantly, but levels 
      of both AUC2-95 and CLtot were not significantly different as compared with the 
      control group. On Day 3, the total P-glycoprotein, including intestinal 
      P-glycoprotein, might have been induced by sepsis, and then the excretion of 
      P-glycoprotein substrate drugs into the intestinal lumen increased more than that 
      of the control group. On Day 7, all pharmacokinetic parameters returned to the 
      control level. Thus the intestinal P-glycoprotein function recovered within 3 
      days of LPS administration.
FAU - Moriguchi, Jun
AU  - Moriguchi J
AD  - Department of Clinical Pharmacy & Clinical Pharmacokinetics, Osaka University of 
      Pharmaceutical Sciences, 4-20-1 Nasahara, Takastuki, Osaka 569-1043, Japan.
FAU - Kato, Ryuji
AU  - Kato R
FAU - Nakagawa, Machiko
AU  - Nakagawa M
FAU - Hirotani, Yoshihiko
AU  - Hirotani Y
FAU - Ijiri, Yoshio
AU  - Ijiri Y
FAU - Tanaka, Kazuhiko
AU  - Tanaka K
LA  - eng
PT  - Journal Article
DEP - 20070312
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (FoxC2a protein, Xenopus)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Xenopus Proteins)
RN  - 1N3CZ14C5O (Rhodamine 123)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 1/*analysis
MH  - Animals
MH  - Forkhead Transcription Factors/pharmacokinetics
MH  - Intestinal Mucosa/metabolism
MH  - Intestines/*drug effects
MH  - Lipopolysaccharides/*toxicity
MH  - Male
MH  - Permeability
MH  - Rats
MH  - Rats, Wistar
MH  - Rhodamine 123/metabolism
MH  - Xenopus Proteins/pharmacokinetics
EDAT- 2007/04/03 09:00
MHDA- 2007/07/27 09:00
CRDT- 2007/04/03 09:00
PHST- 2006/12/03 00:00 [received]
PHST- 2007/02/13 00:00 [revised]
PHST- 2007/02/15 00:00 [accepted]
PHST- 2007/04/03 09:00 [pubmed]
PHST- 2007/07/27 09:00 [medline]
PHST- 2007/04/03 09:00 [entrez]
AID - S0014-2999(07)00310-X [pii]
AID - 10.1016/j.ejphar.2007.02.058 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2007 Jun 22;565(1-3):220-4. doi: 10.1016/j.ejphar.2007.02.058. 
      Epub 2007 Mar 12.