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

PRIESTLY, BRIAN G. AND GAIMUEL L. Pit: Sulfobromophthalein metabolism and excre-tion in rats with iodomethane-induced depletion of hepatic glutathione. J. Pharmacol. Exp. Ther. 174: 221-231, 1970. Pretreatment of rats with iodomethane (75 mg/kg p.o.) resulted in a depletion of hepatic glutathione with no observable change in hepatic ultra-structure. 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 biiary 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