Clinical trial: modulation of human placental multidrug resistance proteins in cholestasis of pregnancy by ursodeoxycholic acid

• Published in: Alimentary pharmacology & therapeutics Vol. 26; no. 8; pp. 1139 - 1146
• Main Authors: AZZAROLI, F., MENNONE, A., FELETTI, V., SIMONI, P., BAGLIVO, E., MONTAGNANI, M., RIZZO, N., PELUSI, G., DE ALOYSIO, D., LODATO, F., FESTI, D., COLECCHIA, A., RODA, E., BOYER, J. L., MAZZELLA, G.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 15.10.2007; Blackwell
• Subjects: ATP Binding Cassette Transporter, Sub-Family B - metabolism; ATP Binding Cassette Transporter, Sub-Family B - pharmacokinetics; Bile Acids and Salts - blood; Bilirubin - blood; Biological and medical sciences; Digestive system; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Infant, Newborn; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Other diseases. Semiology; Pharmacology. Drug treatments; Placenta - blood supply; Placenta - drug effects; Placenta - metabolism; Pregnancy; Pregnancy Complications - blood; Ursodeoxycholic Acid - pharmacology; Ursodeoxycholic Acid - therapeutic use; Human; Placental protein; Treatment resistance; Biliary tract disease; Ursodeoxycholic acid; Pregnancy; Bile acid; Modulation; Multiple resistance; Cholostasis; Digestive diseases; Clinical trial; Female
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1111/j.1365-2036.2007.03462.x

Summary Background  The effects of ursodeoxycholic acid on human placental bile acids and bilirubin transporters in intrahepatic cholestasis of pregnancy are still undefined. Aim  To evaluate whether ursodeoxycholic acid affects MRP2, MRP3 and MRP4 expression in the placenta. Materials and 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.