The effects of supra-therapeutic doses of rifampicin on liver function in the perfused rat liver

Abstract

The isolated liver perfusion model was used to study the effects of supra-therapeutic doses of rifampicin on hepatic gluconeogenesis and bromosulphthalein (BSP) clearance from the perfusate and biliary excretion of the dye in the rat. Three groups of rats randomly assigned to a control and two experimental groups were studied; those in the experimental groups were given 4 mg rifampicin per os daily for 90 days. The control group was untreated. The livers of the control and one experimental group were perfused with a medium containing pyruvate and subsequently these livers were perfused with a medium containing bromosulphthalein. The livers of the second experimental group were subjected to histological examination. The rate and the concentration of glucose was decreased, lactate levels and lactate: pyruvate ratios were increased in the experimental animals. The mean perfusate BSP and biliary excretion of the dye was decreased in the experimental group. Fatty change was present in the livers of rifampicin treated rats. This study demonstrates that the isolated liver model has proved to be both suitable and useful for the study of the effects of drugs and that chronic administration of supra-therapeutic doses of rifampicin to rats adversely affected liver function. It also produces histological evidence of hepatic damage in rats.