Suppression of proliferative cholangitis in a rat model by local delivery of paclitaxel

Abstract

Background. Proliferative cholangitis (PC) leads to biliary stricture, which is the main cause of hepatolithiasis, recurrent cholangitis, and biliary cirrhosis. The aim of this study was to determine whether local delivery of paclitaxel, which inhibits cell proliferation by overstabilization of microtubules, prevents PC in a rat model.

Methods. PC was induced by introducing a fine nylon thread into the bile duct in a rat. Paclitaxel (100 µl of 10, 100, and 1000 µmol/l) or solvent vehicle was administered into the bile duct for 15 min. One week after treatment, histopathologic examination and 5-bromodeoxyuridine (BrdU) labeling of the bile duct were performed.

Results. In comparison with the control, the mean thickness of the bile duct was reduced by 29% in the 1000 µmol/l paclitaxel-treated group (2.61 ± 0.31 µm vs 3.67 ± 0.25 µm, P ≪ 0.05). The luminal area increased (P ≪ 0.0001) and the grade of epithelial–glandular proliferation was decreased (P ≪ 0.01) as the dose of paclitaxel increased. Ductal fibrosis and inflammatory cell infiltration were similar in both groups. The BrdU labeling index was significantly lower in the paclitaxel-treated group (P ≪ 0.05).

Conclusions. Local delivery of paclitaxel suppressed PC in a rat model by the inhibition of epithelial–glandular proliferation and may offer an effective therapeutic option for biliary stricture.