Increase in hepatic mixed disulphide and glutathione disulphide levels elicited by paraquat |
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Authors: | Regina Brigelius Romana Lenzen Helmut Sies |
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Affiliation: | Institut für Physiologische Chemie I, Universität Düsseldorf, Düsseldorf, West Germany |
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Abstract: | Paraquat (1 mM), when added to isolated haemoglobin-free perfused rat liver, leads to an increase of intracellular mixed disulphides from 1.3 μmole GSH equivalents per g wet weight in the controls to 2.5 μmole/g. This raises the proportion of mixed disulphides to total glutathione equivalents from about 0.2 at the beginning of the perfusion to about 0.4. The mixed disulphides are predominantly protein-bound, with low molecular weight compounds being quantitatively negligible.The content of intracellular glutathione disulphide (GSSG) is increased from 17 nmole/g in the controls to 38 nmole/g in the presence of paraquat. In addition, there is an increased rate of release of GSSG into the extracellular (biliary) space, reported previously.It is suggested that, in a reaction catalysed by thioltransferase(s), the rise in GSSG is correlated with the rise in mited disulphides (reaction 1). Occupancy of potential cellular mixed disulphide sites is about in the controls, and rises to about in the presence of paraquat.The ratio of cellular contents, NADPH/NADP+, is decreased from 5.1 in the controls to 2.3 in the presence of paraquat, while the sum of NADPH plus NADP+ remains unaltered.The perturbation in the glutathione status may be related to metabolic effects such as the stimulation of the pentose-phosphate pathway activity, and possibly also to the expression of toxic effects. |
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