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Interference with hepatocellular substrate uptake by 1,1,1-trichloroethane and tetrachloroethylene
V Kukongviriyapan1, U Kukongviriyapan, N H Stacey
1National Institute of Occupational Health and Safety, University of Sydney, NSW, Australia.
Toxicology and Applied Pharmacology
|January 1, 1990
Summary
Chlorinated solvents like 1,1,1-trichloroethane and tetrachloroethylene impair liver cell transport of essential nutrients. This occurs at non-damaging levels by affecting energy processes and cell membrane pumps.
Area of Science:
- Hepatology
- Toxicology
- Cellular Physiology
Background:
- Chlorinated aliphatic hydrocarbon solvents are common environmental contaminants.
- Hepatocellular transport is crucial for liver function and detoxification.
- Previous studies have not fully elucidated the specific mechanisms of solvent-induced transport inhibition.
Purpose of the Study:
- To investigate the impact of 1,1,1-trichloroethane and tetrachloroethylene on hepatocellular transport of model substrates.
- To determine the cellular mechanisms underlying solvent-induced inhibition of hepatic transport.
- To assess the reversibility and dose-dependency of these effects.
Main Methods:
- Isolated hepatocyte exposure to 1,1,1-trichloroethane and tetrachloroethylene.
- Measurement of substrate uptake (taurocholate, ouabain, 2-aminoisobutyric acid, CdCl2, 3-O-methyl-D-glucose).
- Assessment of cell viability (enzyme leakage, K+ concentration), cell ultrastructure, cellular ATP levels, and plasma membrane ATPase activities.
Main Results:
- Solvent exposure suppressed the uptake of energy-dependent substrates (taurocholate, ouabain, 2-aminoisobutyric acid) at non-cytotoxic concentrations.
- No significant effect on the uptake of non-energy-dependent substrates (CdCl2, 3-O-methyl-D-glucose).
- Reduced cellular ATP levels and inhibited Na(+)-K(+)- and Mg2(+)-ATPase activities were observed, with reversibility upon recovery time.
Conclusions:
- 1,1,1-trichloroethane and tetrachloroethylene specifically interfere with energy-dependent hepatic transport functions.
- Decreased ATP levels and/or inhibition of cell membrane ATPases are likely mechanisms of solvent-induced transport disruption.
- These findings highlight potential risks to liver function from exposure to these common solvents.