SULFOBROMOPHTHALEIN METABOLISM AND EXCRETION IN RATS WITH IODOMETHANE-INDUCED DEPLETION OF HEPATIC GLUTATHIONE

¹ Department of Pharmacology, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada

Pretreatment of rats with iodomethane (75 mg/kg p.o.) resulted in a depletion of hepatic glutathione with no observable change in hepatic ultrastructure. When sulfobromophthalein (BSP) was infused (2.5 mg/mm/kg) i.v., the biliary concentration of total BSP was significantly lower in iodomethane-treated rats than in untreated controls. Although the ability of the hepatic enzyme system to catalyze BSP-glutathione conjugation in vitro was not impaired, depletion of the hepatic substrate, glutathione, by pretreatment with iodomethane produced lower biliary concentrations of BSP-glutathione and higher biiary concentrations of unconjugated BSP. A similar, although less pronounced, effect on BSP excretion was observed when single doses (20 mg/kg) were rapidly injected. However, when larger doses (60 mg/kg) were injected, there was no difference between control and iodomethane-treated groups. Iodomethane had no effect on the biliary excretion of synthetically conjugated BSP in infusion experiments, nor did phenoldibromphthalein disulfonate, an analog excreted without conjugation, in either infusion or single dose experiments. The hepatic uptake of BSP does not seem to be affected by iodomethane pretreatment; there was no change in plasma disappearance after injection of single doses and hepatic storage was increased in infusion experiments. The results indicate that, under certain circumstances, interference with hepatic conjugation of BSP can significantly modify its biiary excretion.