Hideaki Fujisaki, Kiyoshi Oketani, Jun-ichi Nagakawa, Osamu Takenaka
and Yoshiharu Yamanishi
Tsukuba Research Laboratories, Eisai Co., Ltd., 1-3, Tokodai 5-chome,
Tsukuba, Ibaraki 300-2635, Japan
Abstract: The effects of rabeprazole (E3810), omeprazole and
chloroquine on hepatic lysosomal function were studied. After chloroquine
(50 mg/kg), rabeprazole (5 mg/kg) or omeprazole (5 mg/kg) was given intraperitoneally
to rats for 6 days, the bile was collected via a bile duct cannula for 5
hr, and hepatic and biliary lysosomal enzyme (N-acetyl-beta-glucosaminidase
and beta-galactosidase) activities were measured. The latency (an index
for the hepatic lysosomal membrane integrity) was calculated from the N-acetyl-beta-glucosaminidase
activity. The biliary constituents and plasma concentrations of lipids were
also measured. The administration of chloroquine significantly increased
hepatic and biliary lysosomal enzyme activities, but did not affect the
lysosomal enzyme latency, hepatic and biliary protein content or bile flow.
It significantly decreased the bile acid level. On the other hand, the administration
of rabeprazole and omeprazole did not alter the lysosomal enzyme activities,
lysosomal enzyme latency, protein content in liver or liver weight. Furthermore,
no significant differences were observed in biliary lysosomal enzyme activity,
protein content, bile flow, biliary constituents or in the plasma concentrations
of lipids between the drug groups (rabeprazole or omeprazole) and the control
group. The results of the present study indicate that rabeprazole, like
omeprazole, does not influence hepatic lysosomal function.
Keywords: Rabeprazole, H+,K+-ATPase inhibitor,
Chloroquine, Lysosomal enzyme, Biliary secretion