Functional impairment of sinusoidal membrane transport of organic cations in rats with CCl4-induced hepatic failure.
OBJECTIVE
The effect of CCl4-induced experimental hepatic failure (EHF) on the sequential hepatobiliary transport of model organic cations (OCs), triethylmethylammonium (TEMA), and tributylmethylammonium (TBuMA), was investigated in rats.


METHODS
EHF was induced by an i.p. injection of CCl4 at a dose of 1 ml/kg 24 hr prior to the transport study. The cumulative in vivo biliary excretion, in vitro hepatic uptake by isolated hepatocytes, in vitro efflux (i.e., release) from hepatocytes, and in vivo hepatobiliary excretion clearance were measured for normal and CCl4-EHF rats.


RESULTS
The CCl4-EHF decreased the apparent in vivo biliary clearance (CL(b)) and the in vitro maximum uptake rate (Vmax, uptake) of TBuMA by 66 and 48%, respectively. The CCl4-EHF had no effect on the CL(b) of TEMA. but decreased both the Vmax, uptake (59%) and the in vitro maximum hepatic efflux rate (Vmax, efflux) of TEMA (80%). On the contrary, the CCl4-EHF had no influence on the in vivo hepatobiliary excretion clearance (CL(exc)) of both OCs.


CONCLUSIONS
Transport systems for the OCs on the sinusoidal membrane (uptake and/or efflux), rather than those on the bile canalicular membrane (excretion) appear to be prone to damage by the CC14-EHF.
Hong
S S
SS
Department of Pharmaceutics, College of Pharmacy, Seoul National University, Korea.
Chung
S J
SJ
Shim
C K
CK
D000818:Animals; D002251:Carbon Tetrachloride; D002412:Cations / Q000493:pharmacokinetics*; D022781:Hepatocytes / Q000378:metabolism*; D017093:Liver Failure / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D000644:Quaternary Ammonium Compounds / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002412:Cations; D000644:Quaternary Ammonium Compounds; C043900:triethylmethylammonium; C043902:tri-n-butylmethylammonium; D002251:Carbon Tetrachloride