EFFECT OF SPIRONOLACTONE, PREGNENOLONE-16-CARBONITRILE AND CORTISOL ON THE METABOLISM AND BILIARY EXCRETION OF SULFOBROMOPHTHALEIN AND PHENOL-3,6-DIBROMOPHTHALEIN DISULFONATE IN RATS

¹ Institut de médecine et de chirurgie expérimentales, et département de pathologic, Université de Montréal, Montreal, Quebec, Canada

In rats, pretreatment with equimolar doses of spironolactone or pregnenolone-16- carbonitrile increases the elimination of sulfobromophthalein (BSP) from blood. These steroids enhance bile flow, hepatic BSP storage, enzymic BSP-glutathione conjugation and biliary BSP excretion. Spironolactone and pregnenolone-16-carbonitrile also increase the hepatic removal and storage as well as the biliary clearance of phenol-3 , 6-dibromophthalein disulfonate, a dye which is not metabolized in the liver before its elimination. Cortisol enhances bile flow and accelerates the hepatic removal and biliary excretion of phenol-3 , 6-dibromophthalein disulfonate without affecting glutathione conjugation or any of these steps in the metabolism and elimination of BSP. Our findings demonstrate the importance of bile flow in the clearance of phenol-3, 6-dibromophthalein disulfonate and underline the significance of enzymic glutathione conjugation in the excretion of large doses of BSP.