Effects of SH-blocking Compounds on the Energy Metabolism in Isolated Rat Hepatocytes

J.H. Boot
1995 Cell Structure and Function  
To investigate the importance of SH-groups in the energy metabolism of liver cells, isolated rat hepatocytes were exposed to various SH-blocking compounds.After 1.0 hr exposure, the cells were analyzed for the content of glycogen, lactate, pyruvate, ATPand the rate of oxygen consumption. Without affecting the cell viability, PCMB, PCMBS,mersalyl, NEM,DTP and DSF were found to decrease glycogen levels, whereas the disulphide reagent CDPSdid not affect this endogenous energy reserve. Lactate and
more » ... yruvate levels were decreased by the organic mercury compounds, whereas NEM,DTPand DSFstimulated the formation of lactate, without affecting the levels of pyruvate. In both situations the oxygen consumption was slightly decreased. The FCCPuncoupled oxygen consumption was not affected. Up to the point of loss of cell viability, as measured by trypan blue exclusion and LDHleakage, the liver cells maintained their ATPlevels, during exposure to the various SH-reagents. In conclusion, the results with organic mercurycompoundssuggest a reaction of these agents with SH-groups in the outer membraneof cells, having an inhibiting effect on the glucose uptake. The most prominent effect of DTP, DSF and NEMwas an increased lactate formation, implying an intracellular effect, most probably in the TCA-cycle. Hepatocytes in short-term and primary cultures are now being widely used as hepatic model systems for toxicity assessment. Hepatocytes in primary culture are a stable, reproducible experimental system, available for studies of prolonged duration. Hepatocytes in short term cultures are a convenient experimental model for studying the acute toxicity of chemicals (Guillouzo, 1986) . Both in vitro systems are well-defined experimen-
doi:10.1247/csf.20.233 fatcat:6bjtra4fsvdzphxrob26qmq6mq