Ouabain lethality as a measure of biliary function in developing mice and rats and effect of polybrominated biphenyls

Abstract

Ouabain is excreted by the liver into the bile in rats and mice. Furthermore, newborn rats are immature in their ability to excrete ouabain and are particularly susceptible to ouabain toxicity. The purpose of this study was to determine whether or not newborn mice are also sensitive to ouabain toxicity, whether or not ouabain toxicity is a suitable index of biliary function, and whether or not perinatal exposure to polybrominated biphenyls (PBBs) results in altered hepatic function in rats and mice. Ouabain toxicity was assessed by determining 24-hr LD50 values and the hepatic excretion of ouabain was determined by measuring radioactivity in plasma, liver, and intestine following a single injection of [ 3H]ouabain in mice and rats of various ages. The LD50 of ouabain in 10-day-old mice was 1.85 mg/kg (ip) and increased with age until the animals were 18 days of age when LD50 values were the same as values obtained from adults (16.50 mg/kg). In addition, following ip injection of [ 3H]ouabain, plasma concentrations of ouabain were higher in young mice relative to adults. Treatment with PBBs through the mother's diet did not affect ouabain LD50 values in 15-day-old mice but did result in a significant increase in liver weight and enhanced disappearance of ouabain from the plasma in these animals. In developing rats exposed to PBBs, a similar enhancement of liver weight and hepatic transport of ouabain was observed; however, in rats, enhanced ouabain transport correlated with protection against ouabain toxicity. These results suggest that ouabain lethality is not a good index of biliary function in developing mice. However, ouabain toxicity can be used to estimate hepatic function in rats. In this regard, perinatal exposure to PBBs resulted in a significant drug (ouabain) interaction.