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Functional Impairment of Sinusoidal Membrane Transport of Organic Cations in Rats with CCl4-Induced Hepatic Failure

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Abstract

Purpose. The effect of CCl4-induced experimental hepatic failure(EHF) on the sequential hepatobiliary transport of model organiccations (OCs), triethylmethylammonium (TEMA), and tributylmethylammonium (TBuMA), was investigated in rats.

Methods. EHF was induced by an i.p. injection of CCl4 at a dose of1 ml/kg 24 hr prior to the transport study. The cumulative in vivobiliary excretion, in vitro hepatic uptake by isolated hepatocytes,in vitro efflux (i.e., release) from hepatocytes, andin vivo hepatobiliary excretion clearance were measured for normal and CCl4-EHF rats.

Results. The CCl4-EHF decreased the apparentin vivo biliary clearance (CLo) and the in vitromaximum uptake rate (Vmax, uptake) of TBuMA by 66 and 48%,respectively. The CCl4-EHF had no effect on the CLoof TEMA, but decreased both the Vmax, uptake (59%) and thein vitromaximum hepatic efflux rate (Vmax, efflux) of TEMA (80%). On thecontrary, the CCl4-EHF had no influence on the in vivohepatobiliaryexcretion clearance (CLexc) of both OCs.

Conclusions. Transport systems for the OCs on the sinusoidal membrane(uptake and/or efflux), rather than those on the bile canalicularmembrane (excretion) appear to be prone to damage by the CCl4-EHF.

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Authors and Affiliations

  1. Department of Pharmaceutics, College of Pharmacy, Seoul National University, Seoul, 151-742, Korea

    Soon-Sun Hong & Suk-Jae Chung

  2. Department of Pharmaceutics, College of Pharmacy, Seoul National University, Seoul, 151-742, Korea

    Chang-Koo Shim

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  1. Soon-Sun Hong
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  2. Suk-Jae Chung
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Hong, SS., Chung, SJ. & Shim, CK. Functional Impairment of Sinusoidal Membrane Transport of Organic Cations in Rats with CCl4-Induced Hepatic Failure. Pharm Res 17, 833–838 (2000). https://doi.org/10.1023/A:1007508325512

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  • DOI: https://doi.org/10.1023/A:1007508325512

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