Hepatic toxicity of paraquat in primary cultures of rat hepatocytes.
The aim of this work was to evaluate the hepatic effects of toxic and subtoxic doses of paraquat, using a primary culture of adult rat hepatocytes as an experimental model. Concentrations in culture ranged from 10(-3) to 10(-9)m-paraquat. When added to cultures at the time of plating 10(-3)m-paraquat impaired hepatocyte spreading on the substratum and caused cell death which was preceded by a leakage of cytosolic enzymes (lactate dehydrogenase, glutamic-oxaloacetic transaminase). When added to 24-hr cultures, effects on the metabolism of the hepatocytes were observed at paraquat concentrations of 10(-3) and 10(-4)m but not at lower concentrations. In comparison with controls, when paraquat was present at 10(-3)m, gluconeogenesis from fructose and lactate was inhibited by 40 and 58%, respectively, ureogenesis was inhibited by 16% and the albumin synthesis rate was reduced by 62%. The intracellular content of the reduced form of glutathione decreased by 33% and was parallelled by an increase in the oxidized form of glutathione. However, neither cytotoxic nor metabolic effects were observed in cells exposed to 10(-5)m, the concentration found in blood after acute intoxication with paraquat.
Masanet
J
J
Centro de Investigación, Hospital La Fe, Instituto Nacional de la Salud, Avenida de Campanar 21, 46009 Valencia, Spain.
Gómez-Lechón
M J
MJ
Castell
J V
JV