This study investigated the effect of trimetazidine (TMZ), known as an anti
-oxidant agent, on intrahepatic cholestasis caused by Carmustine (BCNU) in
rats. Rats were assigned into four groups. The first group (Saline) consist
ed of 12 rats, which were injected with 2 ml/kg of saline intraperitoneally
(IP) 48 h before the study. The second group (corn oil group, n = 15), whi
ch were injected with 2 ml/kg of corn oil IP 48 h before the study. The thi
rd group (BCNU group, n = 16), which were injected with 2 ml/kg of corn oil
+ 25 mg/kg BCNU IP 48 h before the study. The fourth group (TMZ group, n =
12), which were injected with 2.5 mg/kg per day of TMZ IF, administered at
the same hour of the day as a single-dose. Twelve hour after the first dos
e of TMZ, corn oil 2 ml/kg + BCNU 25 mg/kg IP were injected, and the rats w
ere included in the study 48 h after the administration of corn oil + BCNU.
Following a pentobarbital anaesthesia, abdomen was opened with incision, a
cannula was placed into the channel of choledocus, and the amount of bile
was measured per hour. Then intracardiac blood sample was taken, and conseq
uently centrifuged to obtain the plasma. Finally, the rats were killed with
cervical dislocation, and their livers were removed and weighted. In addit
ion to histopathological examination of liver, the levels of malon dialdehy
de (MDA), oxidised glutation (GSSG), and reduced glutation (GSH) were detec
ted. Also the osmolality of bile and plasma was estimated in mOsm/kg. As a
result, the biliary flow was seen to decrease in BCNU group (P < 0.005), bu
t to be normal in TMZ group. The serum level of conjugated biluribin was hi
gher in BCNU group compared to other groups (P < 0.05 for each). Although t
he level of total glutation was lower (P < 0.005) in TMZ group, GSH/GSSG ra
tio was normal. These findings suggest that TMZ has a protective effect on
intrahepatic cholestasis caused by BCNU. <(c)> 2001 Elsevier Science Irelan
d Ltd. All rights reserved.