Bromsulphalein (BSP) kinetics in the rat: a new approach in evaluating experimental hepatotoxicity

An animal model for the identification and definition of toxic liver damage, based on the investigation of the BSP metabolism in the rat is proposed. Different hepatotoxins can induce specific functional alteration on the different steps of the BSP hepatobiliary transport, mainly the uptake by hepatocytes and the biliary excretion. Removal curves of BSP from the plasma compartment as well as the biliary secretion were evaluated in rats treated with either alpha-naphthylisothiocyanate (ANIT) for metabolic cholestasis, or with carbon tetrachloride (CCl4) for fatty infiltration and necrosis of the liver. The data were compared with those obtained with untreated rats and with animals submitted either to complete or incomplete mechanically induced cholestasis. Our results lead to the conclusion that a satisfactory discrimination among different types of liver damage may be obtained when only two plasma parameters of BSP metabolism are considered: the disappearance rate for the early 5 min (K), and 15-min plasma BSP retention (R15). The model is proposed as a suitable tool for the evaluation of experimental hepatotoxicity in living rats giving a characterisation of the functional alteration and a measure of liver impairment.