Relation between renal and hepatic excretion of drugs: V. Factors influencing accumulation of phenol red in kidney and liver tissues from rats of different ages

Abstract

Following bile duct ligation (DL) or bilateral nephrectomy (NX), phenol red accumulation in kidney or liver tissue, respectively, is reduced in rats of different ages. This is in contrast to in vivo experiments showing a compensatory increase of renal or hepatic excretion of phenol red in adult rats after DL or NX, respectively. The present study was performed to clarify this discrepancy. Three possible reasons were taken into consideration: 1. competition between accumulation of phenol red and bilirubin or bile acids; 2. influence of humoral factors occurring in serum of DL-rats on accumulation capacity; 3. changes of phenol red binding in homogenate of the kidney cortex or liver tissue after DL or NX. Ad 1. There exist inhibitory effects of bilirubin and cholic acid on phenol red accumulation. This inhibition is a competitive as well as a toxic one, apparently caused by a reduction of intracellular phenol red binding. Similar results have been obtained in in vivo experiments. During continuous infusion of bilirubin both renal and hepatic excretion of phenol red is significantly diminished. Ad 2. Incubation of tissue slices of control animals in serum of DL-rats does not indicate the existence of humoral factors reducing accumulation of phenol red after DL. Only in adult rats the plasma protein binding of phenol red is reduced after DL; in 10-day-old rats the binding capacity of the proteins for the dye is unchanged after DL. Ad 3. In young animals the phenol red binding on tissue homogenate is significantly reduced after DL or NX in kidney or liver; binding capacity of adult rats' tissue homogenate is unchanged after both operations. It can be concluded that renal and hepatic excretion capacity cannot be increased within a few hours after these blocking operations and obviously a functional reserve of the transport mechanisms does not exist.