Biliary excretion of 3,4-benzpyrene in nafenopin-treated rats

When rats treated for 2 days with nafenopin are injected i.v. with 3H-3,4-benzpyrene (BP), blood disappearance rates and liver levels of the carcinogen and the rate of biliary excretion of its metabolites are, in the main, similar to those of nontreated rats. This is in accord with the observation that nafenopin does not inhibit the metabolism of BP, which is the rate-limiting step in its biliary excretion. On the other hand, when 3H-BP metabolites are injected, nafenopin pretreatment slightly retards their rate of plasma disappearance and markedly inhibits their biliary excretion, as it does other organic anions. When rats are pretreated with 3-methylcholanthrene, the rate of metabolism of 3H-BP and consequently the biliary excretion of its metabolites is greatly stimulated. In this instance, metabolism may no longer be rate-limiting in the overall biliary excretion process and inhibition by nafenopin of liver-to-bile transport of metabolites can be observed. Since nafenopin pretreatment stimulates the synthesis of new liver tissue, it is presently a matter of conjecture as to whether or not the newly formed hepatocytes have the capacity to take up and excrete BP and its metabolites or whether nafenopin inhibits transport in all liver tissue.