Glutathione Efflux from Perfused Rat Liver and Its Relation to Glutathione Uptake by the Kidney

Abstract

The isolated perfused rat liver releases GSH at a rate of 12 nmol/min/g wet wt. at 37°C, whereas the release of GSSG is much lower, 1 nmol/min/g. It has recently become evident that glutathione release from liver may be of significance for glutathione turnover if viewed in conjunction with transport in plasma and degradation by extrahepatic tissues, notably the kidney. We have found that GSH efflux occurs into the caval perfusate, while GSSG efflux occurs into bile, so that GSH efflux into plasma may also occur in vivo. Assuming that GSH release from liver occurs at a rate of 12 nmol/min/g liver also in the intact animal, it is calculated that the glutathione pool designated as the “labile pool” with a half-life time of 1.7 h would have a pool size of 1.8 μmol/g liver, amounting to approximately one-third of the glutathione content. If, on the other hand, the total glutathione pool would contribute to the efflux, the half-life time would have to be approximately 5.2 h. In order to estimate the capacity of renal plasma glutathione degradation, arterial and renal venous plasma glutathione concentrations were determined in samples obtained from anaesthetized rats. The glutathione concentration in arterial plasma was 3.1 μM (expressed in GSH equivalents), and the renal venous plasma value was 88% lower. This indicates that glutathione uptake by the kidney occurs not only by glomerular filtration and subsequent degradation by the γ-glutamyltranspeptidase of the tubular brush border membrane, but also by an additional uptake mechanism. The rate of glutathione uptake is limited by the renal plasma flow, since the glutathione extraction (%) was similar to the controls in rats receiving a GSH infusion to result in arterial plasma values up to 0.6 mM. It is concluded from these data that the GSH release observed in the perfused liver is compatible with the in vivo half-life time, and that the kidney has the capacity to extract a significant part of the plasma glutathione. However, a calculation with the renal plasma flow rates indicates that organs other than the kidney also play a role in plasma glutathione turnover.