Effect of penicillin G on the biliary excretion of cholephilic compounds in rats

Abstract

Penicillin G is reported to increase bile flow by increasing biliary glutathione excretion, as well as the biliary excretion of penicillin G itself. In order to study the effect of penicillin G on the hepatic excretory pathway, the effect of colchicine and genipin on the increase of biliary glutathione excretion induced by penicillin G was studied in rats. The effect of penicillin G on the biliary excretion of sulfobromophthalein and erythromycin was also studied, together with the effect of penicillin G on cholestasis induced by estradiol-17β-glucuronide. After bile duct cannulation, penicillin G was administered to rats at the rate of 0.5 μmol/min/100 g. The effect was examined of colchicine pretreatment (0.2 mg/100 g) and genipin administration (0.5 μmol/min/100 g) on biliary glutathione excretion increased by penicillin G infused at the rate of 0.5 μmol/min/100 g. The effect of penicillin G on the biliary excretion of sulfobromophthalein and erythromycin (0.2 and 0.1 μmol/min/100 g for 90 min, respectively) was studied, together with the effect of penicillin G on cholestasis induced by estradiol-17β-glucuronide (0.075 μmol/min/100 g for 20 min). Penicillin G increased bile flow and biliary glutathione excretion, which were not inhibited by colchicine or genipin. Biliary penicillin G excretion was markedly reduced in Eisai hyperbilirubinemic rats (EHBR) and Mrp2-deficient rats. Biliary sulfobromophthalein and erythromycin excretion was unchanged by penicillin G. Cholestasis induced by estradiol-17β-glucuronide was not relieved by penicillin G. It was shown that colchicine-sensitive vesicular transport has no role on the penicillin G-induced insertion of Mrp2 into the canalicular membrane, as has been observed with genipin. Although the choleresis of penicillin G is thought to be due to the increased biliary excretion of glutathione and penicillin G itself by Mrp2, the mechanism of Mrp2 insertion by penicillin G is thought to be partly different from that by genipin.