Effect of oxygen shortage on the metabolism of oestrone in the hemoglobin-free perfused rat liver

Abstract

The isolated rat liver was perfused with a haemoglobin-free, albumin containing salt solution at 28 degrees and 37 degrees C, respectively, with [4-14C]oestrone as substrate. During perfusion, the functional state of the liver was checked by continuously measuring the oxygen pressure and hydrogen ion concentration in the perfusion medium, flow rate, oxygen tension at various areas of the liver surface, and oxygen consumption; in addition, the following biochemical parameters were determined: ATP, ADP, lactate and pyruvate in liver tissue, and lactate and pyruvate in the perfusion medium. After 30 min of perfusion, free steroids, steroid glucuronides, steroid sulphates and the remaining water-soluble metabolites, present in liver tissue, perfusion medium and bile, were separated from each other and characterised by thin-layer and paper chromatography. It was found that, during perfusion at 37 degrees C, less hydroxylated metabolites were formed than at 28 degrees C. In contrast, metabolites whose formation is not directly oxygen-dependent, such as glucuronides and sulphates, arose in higher amounts at 37 degrees C than at 28 degrees C. It may be concluded that the relative shortage of oxygen at 37 degrees C leads to a selective impairment of metabolic pathways requiring a sufficient supply of molecular oxygen. Since oxidative processes play an important role in the biogenesis and metabolism of steroid hormones, it is evident that results, obtained in perfusion experiments with haemoglobin-free media at 37 degrees C, must be treated with reserve.