Effects of lipopolysaccharide on P-glycoprotein expression and activity in the liver and kidneys.
There have been many reports that P-glycoprotein expression and activity are altered during sepsis, but few of them have examined such changes over 72 h. In this study, we examined the effect of lipopolysaccharide (LPS, 5mg/kg, ip) on P-glycoprotein expression (Western blotting) and activity (rhodamine-123 (Rho123) pharmacokinetics) in liver and kidneys for 7 days. On day 1 after LPS administration, hepatic P-glycoprotein expression and activity significantly decreased. On day 3, hepatic P-glycoprotein expression significantly increased compared with the control group, while activity had returned to the control level. On day 7, hepatic P-glycoprotein expression returned to the control level. There were no significant changes in P-glycoprotein expression or activity in the kidneys after LPS administration. The amount of Rho123 excretion in urine remained unchanged with (4.2%) or without (4.0%) LPS administration, but the amount of Rho123 excretion in bile decreased from 2.0 to 0.7% with LPS administration. Our findings suggested that hepatic P-glycoprotein expression and activity decreased on day 1 but recovered within 3 days, but there were no significant differences in the kidneys after LPS administration. These results suggested that the change in P-glycoprotein activity might be due to change in P-glycoprotein expression in the liver rather than the kidneys.
Kato
Ryuji
R
Department of Clinical Pharmacy and Clinical Pharmacokinetics, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takastuki, Osaka 569-1094, Japan.
Moriguchi
Jun
J
Irie
Takako
T
Nakagawa
Machiko
M
Kusukawa
Yugo
Y
Matsumura
Hitoshi
H
Ijiri
Yoshio
Y
Tanaka
Kazuhiko
K
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D020112:Rhodamine 123 / Q000008:administration & dosage / Q000097:blood; D013997:Time Factors
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008070:Lipopolysaccharides; D020112:Rhodamine 123