Clinical trial: modulation of human placental multidrug resistance proteins in cholestasis of pregnancy by ursodeoxycholic acid.
BACKGROUND
The effects of ursodeoxycholic acid on human placental bile acids and bilirubin transporters in intrahepatic cholestasis of pregnancy are still undefined.


OBJECTIVE
To evaluate whether ursodeoxycholic acid affects MRP2, MRP3 and MRP4 expression in the placenta.


METHODS
Forty-three pregnant women were enrolled; fourteen subjects had physiological pregnancies. Intrahepatic cholestasis of pregnancy patients were divided into two groups: (i) 13 received ursodeoxycholic acid (20 mg/kg/day) and (ii) 16 untreated. Total bile acid and bilirubin in serum and cord blood were determined in each subject. Multidrug resistance proteins expression (immunoblot, quantitative real-time PCR) was evaluated in placentas collected at delivery. anova test was used for statistical analysis of data.


RESULTS
Ursodeoxycholic acid administration significantly improved maternal serum bile acid and cord blood bilirubin and bile acid levels. MRP2 protein and RNA expression was significantly increased in placentas from treated patients compared to controls (P < 0.001 and P < 0.01, respectively). MRP3 protein expression was not significantly different between the groups while RNA expression was significantly decreased in treated patients (P < 0.01). MRP4 did not show significant differences between the groups.


CONCLUSIONS
Ursodeoxycholic acid administration induces placental MRP2 expression, and reduces bilirubin and bile acid levels in cord blood.
Azzaroli
F
F
Dipartimento di Medicina Interna e Gastroenterologia, Università degli Studi di Bologna, Bologna, Italy/ francesco.azzaroli@unibo.it
Mennone
A
A
Feletti
V
V
Simoni
P
P
Baglivo
E
E
Montagnani
M
M
Rizzo
N
N
Pelusi
G
G
DE Aloysio
D
D
Lodato
F
F
Festi
D
D
Colecchia
A
A
Roda
E
E
Boyer
J L
JL
Mazzella
G
G
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism* / Q000493:pharmacokinetics; D001647:Bile Acids and Salts / Q000097:blood; D001663:Bilirubin / Q000097:blood; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D010920:Placenta / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood*; D014580:Ursodeoxycholic Acid / Q000494:pharmacology / Q000627:therapeutic use*
D018435:ATP Binding Cassette Transporter, Subfamily B; D001647:Bile Acids and Salts; D014580:Ursodeoxycholic Acid; D001663:Bilirubin